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Harigai M, Kaneko Y, Tanaka E, Hirata S, Kameda H, Kaneko K, Kishimoto M, Kohno M, Kojima M, Kojima T, Morinobu A, Nakajima A, Sugihara T, Fusama M, Yajima N, Yanai R, Kawahito Y. 2024 Update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis: Secondary publication. Mod Rheumatol 2025; 35:387-401. [PMID: 39820350 DOI: 10.1093/mr/roaf006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 12/28/2024] [Accepted: 01/15/2025] [Indexed: 01/19/2025]
Abstract
OBJECTIVES The aim of this study is to update the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis (CPG for RA). METHODS The recommendations were developed based on the evidence published until the end of June 2022 using the Grading of Recommendations Assessment, Development, and Evaluation. The steering committee, CPG panel, systematic review (SR) group, and SR support team were organised. RESULTS The treatment goal and drug treatment algorithm required no modifications; however, the footnotes of the drug treatment algorithm were modified. SR of 21 new or updated recommendations for subcutaneous methotrexate (n = 1), biological disease-modifying antirheumatic drugs (n = 1), rituximab (n = 5), Janus kinase inhibitors (n = 6), biosimilars (n = 2), older patients (n = 4), and pregnancy and lactation (n = 2) was conducted. The recommendations for comorbidities and surgery and rehabilitation remained unchanged from the 2020 CPG for RA. CONCLUSIONS The 2024 CPG for RA, which provide recommendations that reflect the current healthcare environment for rheumatoid arthritis in Japan, can be used effectively as a tool for shared decision-making between rheumatologists and patients in the treatment of RA.
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Affiliation(s)
- Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Eiichi Tanaka
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Shintaro Hirata
- Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan
| | - Hideto Kameda
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University (Ohashi Medical Center), Meguro-ku, Tokyo, Japan
| | - Kayoko Kaneko
- Division of Maternal medicine, Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
| | - Mitsumasa Kishimoto
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Masataka Kohno
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto-shi, Kyoto, Japan
| | - Masayo Kojima
- Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Toshihisa Kojima
- Orthopaedic Surgery and Rheumatology, National Hospital Organization, Nagoya Medical Center, Nagoya-shi, Aichi, Japan
| | - Akio Morinobu
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Ayako Nakajima
- Department of Rheumatology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Takahiko Sugihara
- Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, Japan
| | - Mie Fusama
- Health Sciences Department of Nursing, Kansai University of International Studies, Miki, Hyogo, Japan
| | - Nobuyuki Yajima
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan
| | - Ryo Yanai
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan
| | - Yutaka Kawahito
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto-shi, Kyoto, Japan
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Jarab AS, Abu Heshmeh SR, Al Meslamani AZ. Biosimilars and immunogenicity: a matter of concern? Expert Opin Drug Saf 2025:1-9. [PMID: 39955621 DOI: 10.1080/14740338.2025.2467817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 01/29/2025] [Indexed: 02/17/2025]
Abstract
INTRODUCTION Biosimilars have transformed treatment modalities across various medical fields such as oncology, rheumatology, and immunology. Despite their potential for reducing healthcare costs, concerns persist regarding their ability to induce an immune response, which could affect efficacy and safety. This review critically evaluates the current evidence on the immunogenicity of biosimilars and discusses the regulatory frameworks guiding their approval and monitoring. AREAS COVERED This review includes studies from databases like Scopus, PubMed, Web of Science, and ScienceDirect, published up to April 2024. It explores the 'totality of the evidence' approach used by regulatory bodies like the FDA and EMA, detailing analytical, preclinical, and clinical assessments that ensure biosimilars' similarity to their reference products in terms of structure, function, and clinical outcomes. The review also addresses the challenges and limitations in current research methodologies and the implications of immunogenicity on therapeutic efficacy and patient safety. EXPERT OPINION While substantial evidence confirms the safety and efficacy of biosimilars, the review emphasizes the need for continuous regulatory vigilance and advanced methodologies in post-marketing surveillance to capture long-term immunogenicity data effectively. It advocates for integrating cutting-edge analytical techniques and personalized medicine to better manage immunogenic risks associated with biological therapies.
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Affiliation(s)
- Anan S Jarab
- College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
| | - Shrouq R Abu Heshmeh
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad Z Al Meslamani
- College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
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Nakayama Y, Nagata W, Takeuchi Y, Fukui S, Fujita Y, Hosokawa Y, Ueno M, Ono K, Sumitomo S, Tabuchi Y, Nakanishi Y, Saito S, Ikeuchi H, Kawamori K, Sofue H, Doi G, Minami R, Hirota T, Minegishi K, Maeshima K, Motoyama R, Nakamura S, Suzuki S, Nishioka N, Wada TT, Onishi A, Nishimura K, Watanabe R, Yanai R, Kida T, Nishiwaki H, Yajima N, Kaneko Y, Tanaka E, Kawahito Y, Harigai M. Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis. Mod Rheumatol 2024; 34:1079-1094. [PMID: 38814660 DOI: 10.1093/mr/roae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/03/2024] [Accepted: 05/15/2024] [Indexed: 05/31/2024]
Abstract
OBJECTIVES The aim of this article is to update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA). METHODS We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, two independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to conventional synthetic DMARD (csDMARD). Rituximab with and without concomitant csDMARDs showed similar efficacy to other biological DMARDs (bDMARDs) in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSIONS This systematic review provides latest evidence for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for RA management.
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Affiliation(s)
- Yoichi Nakayama
- Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Wataru Nagata
- Department of Pharmacology, National Defense Medical College, Tokorozawa, Japan
| | - Yoichi Takeuchi
- Department of Rheumatology and Nephrology, Japanese Red Cross Maebashi Hospital, Maebashi, Japan
| | - Sho Fukui
- Department of Emergency and General Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Yuya Fujita
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yohei Hosokawa
- Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan
| | - Masanobu Ueno
- The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Kumiko Ono
- Department of Joint Surgery, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Shuji Sumitomo
- Department of Rheumatology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Yuya Tabuchi
- Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuichiro Nakanishi
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shuntaro Saito
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hiroko Ikeuchi
- Department of Preventive Services, School of Public Health, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan
| | - Kazutaka Kawamori
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Hideaki Sofue
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Goro Doi
- Department of Internal Medicine, Kyushu University Beppu Hospital, Oita, Japan
| | - Runa Minami
- Department of Orthopaedic Surgery and Rheumatology, Otokoyama Hospital, Kyoto, Japan
| | - Tomoya Hirota
- Department of Infection and Rheumatology, University of Fukui Hospital, Fukui, Japan
| | - Kaoru Minegishi
- Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Ryo Motoyama
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Shohei Nakamura
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Shotaro Suzuki
- Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Norihiro Nishioka
- Department of Preventive Services, School of Public Health, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan
| | - Takuma Tsuzuki Wada
- Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Akira Onishi
- Department of Advanced Medicine of Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kenichi Nishimura
- Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Ryu Watanabe
- Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Ryo Yanai
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Takashi Kida
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroki Nishiwaki
- Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Nobuyuki Yajima
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Eiichi Tanaka
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Yutaka Kawahito
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masayoshi Harigai
- Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
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Sequier L, Caron B, Danese S, Peyrin-Biroulet L. Clinical experience of using biosimilars in Crohn's disease and their effectiveness. Expert Opin Biol Ther 2024; 24:1145-1169. [PMID: 39269146 DOI: 10.1080/14712598.2024.2401616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024]
Abstract
INTRODUCTION The approval of biosimilars in the management of inflammatory bowel diseases (IBDs) has offered an answer to a growing concern about healthcare costs, and availability of treatments. Several studies have been conducted to demonstrate proof of biosimilars effectiveness as treatment in Crohn's disease (CD). AREAS COVERED Since 2013, the European Medicines Agency has approved five biosimilars for infliximab and eight for adalimumab. Initial data leading to approval were extrapolated from studies conducted in patients with rheumatological or dermatological diseases, but recent studies filled the gap of clinical data among patients with IBD. In this review, 75 studies were included, with data from a total of 20 707 patients with CD. Clinical data on biosimilars in the treatment of CD show equivalence in terms of efficacy, either as induction or maintenance of treatment and regardless of previous exposure to originator or other biosimilar. EXPERT OPINION Since biosimilar market entry, utilization of infliximab increased by 89.9% and by 22.4% for adalimumab in European countries. With a 10-year insight since the first approval of biosimilar in Europe, biosimilars prescriptions should be implemented in routine clinical practice given the efficacy and safety profile.
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Affiliation(s)
- Léa Sequier
- Department of Gastroenterology and Hepatology, Nîmes University Hospital, Carémeau Hospital, Nîmes, France
- Department of Gastroenterology and Hepatology A, Saint-Éloi Hospital, Montpellier, France
| | - Bénédicte Caron
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
- Department of Immunology, Transplantation and Infectious Disease, Università Vita-Salute San Raffaele, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
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Zeng Z, Lin H, Jiang M, Yuan J, Li X, Jia Y, Yang L, Zhang H. Anti-TNFα in inflammatory bowel disease: from originators to biosimilars. Front Pharmacol 2024; 15:1424606. [PMID: 39114362 PMCID: PMC11303209 DOI: 10.3389/fphar.2024.1424606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 07/12/2024] [Indexed: 08/10/2024] Open
Abstract
The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review.
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Affiliation(s)
- Zhen Zeng
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Hao Lin
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Mingshan Jiang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Jing Yuan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Xi Li
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yongbin Jia
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Li Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hu Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Sen R, Riofrio M, Singh JA. A narrative review of the comparative safety of disease-modifying anti-rheumatic drugs used for the treatment of rheumatoid arthritis. Expert Opin Drug Saf 2024; 23:687-714. [PMID: 38695151 DOI: 10.1080/14740338.2024.2348575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 04/24/2024] [Indexed: 05/24/2024]
Abstract
INTRODUCTION Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events. AREAS COVERED In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies. EXPERT OPINION DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA.
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Affiliation(s)
- Rouhin Sen
- Division of Clinical Immunology and Rheumatology, The University of Alabama Birmingham, Birmingham, AL, USA
- Medicine/Rheumatology Birmingham Veterans Affairs Medical Center (VAMC), Birmingham, AL, USA
| | - Maria Riofrio
- Division of Clinical Immunology and Rheumatology, The University of Alabama Birmingham, Birmingham, AL, USA
| | - Jasvinder A Singh
- Division of Clinical Immunology and Rheumatology, The University of Alabama Birmingham, Birmingham, AL, USA
- Medicine/Rheumatology Birmingham Veterans Affairs Medical Center (VAMC), Birmingham, AL, USA
- Department of Epidemiology, UAB School of Public Health, Birmingham, AL, USA
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Jourdain H, Hoisnard L, Sbidian E, Zureik M. Persistence and safety of anti-TNF biosimilars versus originators in immune-mediated inflammatory diseases: an observational study on the French National Health Data System. RMD Open 2024; 10:e003531. [PMID: 38453213 PMCID: PMC10921511 DOI: 10.1136/rmdopen-2023-003531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 01/20/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVES Biosimilar-originator equivalence has been demonstrated in phase 3 trials in a few indications of infliximab, etanercept and adalimumab. The objective of our study was to compare the persistence and safety of biosimilars versus originators in all the licensed indications of these molecules. METHODS We used data from the French National Health Data System (SNDS), covering 99% of the French population, to identify infliximab, etanercept and adalimumab initiators from biosimilar launch (January 2015, May 2016 and October 2018, respectively) to 30 June 2021. Patients were then followed for 1 year. Treatment persistence (duration without treatment discontinuation or modification) and safety (including severe infections, all-cause hospitalisation and death) were compared between originator and biosimilar users by Cox regressions weighting the populations on the inverse probability of treatment. Analyses were performed by molecule, by disease and by biosimilar product. RESULTS From January 2015 to June 2021, 86 776 patients were included in the study: 22 670, 24 442 and 39 664 patients had initiated infliximab, etanercept and adalimumab, respectively; 49 752 (53%) were biosimilar initiators. We did not find any risk of discontinuation (HRs were below or around 1, here all pathologies and products together: infliximab 0.88 (0.80-0.97), etanercept 0.85 (0.81-0.90) and adalimumab 0.96 (0.91-1.00)) or safety event (infection: infliximab 0.97 (0.78-1.21), etanercept 1.04 (0.81-1.33) and adalimumab 0.98 (0.83-1.16); hospitalisation: infliximab 1.08 (0.96-1.23), etanercept 0.99 (0.87-1.11) and adalimumab 0.91 (0.83-0.99)) associated with biosimilar versus originator use. CONCLUSIONS Our study shows reassuring results regarding the persistence and safety of biosimilar tumour necrosis factor-alpha inhibitors compared with originators in all licensed indications.
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Affiliation(s)
- Hugo Jourdain
- EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), Saint-Denis, France
| | - Léa Hoisnard
- Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, Créteil, France
- Centre d'Investigation Clinique 1430, INSERM, Créteil, France
- EpiDermE Epidemiology in Dermatology and Evaluation of Therapeutics, EA7379, Paris Est Créteil University UPEC, Créteil, France
| | - Emilie Sbidian
- EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), Saint-Denis, France
- Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, Créteil, France
- Centre d'Investigation Clinique 1430, INSERM, Créteil, France
- EpiDermE Epidemiology in Dermatology and Evaluation of Therapeutics, EA7379, Paris Est Créteil University UPEC, Créteil, France
- Department of Dermatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, Créteil, France
| | - Mahmoud Zureik
- EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), Saint-Denis, France
- Anti-Infective Evasion and Pharmacoepidemiology, CESP, University Paris-Saclay - UVSQ, Montigny le Bretonneux, France
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Baker J, Kalb R. Biosimilars in Dermatology Review. JOURNAL OF PSORIASIS AND PSORIATIC ARTHRITIS 2024; 9:28-35. [PMID: 39301301 PMCID: PMC11361486 DOI: 10.1177/24755303231212154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Background Safe and effective biosimilar medications have the potential to significantly increase access to these valuable drugs. The two current biosimilars available in dermatology in the United States (US) are infliximab and rituximab which were Food and Drug Administration (FDA) approved in 2016 and 2018 respectively. There has been significant interest in this topic as a number of biosimilar versions of adalimumab will be available in 2023. Objective This review will discuss biosimilar basics and the experience with biosimilars used in dermatology in the US, Asia, and Europe. Methods All articles in Ovid/Medline from 2015 to Feb 2023 on biosimilars were reviewed with a particular emphasis on medications used in dermatology. Other reports from pharmaceutical manufacturers and blogs following the development of the biosimilar industry provided key insights. Results Biosimilars have been able to produce significant savings and market share increases, particularly in Europe, where there has been a longer experience. The specifics depend on drug prescribing practices and incentives in the individual country. This degree of savings and market share increases have not been realized with the current biosimilars available in the US. Conclusion While biosimilars have resulted in significant savings compared to originator drugs, it is clear that prescribing incentives and physician education are crucial in achieving these savings. To what degree biosimilar market share will increase in the US remains to be determined.
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Affiliation(s)
- John Baker
- Dermatology Department, University at Buffalo, Buffalo, NY, USA
| | - Robert Kalb
- Dermatology Department, University at Buffalo, Buffalo, NY, USA
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Kazama T, Ando K, Ueno N, Fujiya M, Ito T, Maemoto A, Ishigami K, Nojima M, Nakase H. Long-term effectiveness and safety of infliximab-biosimilar: A multicenter Phoenix retrospective cohort study. PLoS One 2023; 18:e0288393. [PMID: 37699041 PMCID: PMC10497130 DOI: 10.1371/journal.pone.0288393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 06/26/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated. METHODS We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups. RESULTS A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%). CONCLUSION The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.
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Affiliation(s)
- Tomoe Kazama
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Katsuyoshi Ando
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Nobuhiro Ueno
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Takahiro Ito
- Sapporo Higashi Tokushukai Hospital IBD Center, Sapporo, Japan
| | - Atsuo Maemoto
- Sapporo Higashi Tokushukai Hospital IBD Center, Sapporo, Japan
| | - Keisuke Ishigami
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masanori Nojima
- Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
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10
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de Oliveira Ascef B, Almeida MO, de Medeiros-Ribeiro AC, de Oliveira Andrade DC, de Oliveira Junior HA, de Soárez PC. Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis. Sci Rep 2023; 13:13699. [PMID: 37607959 PMCID: PMC10444768 DOI: 10.1038/s41598-023-40222-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 08/07/2023] [Indexed: 08/24/2023] Open
Abstract
What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD - 0.07, 95% CrIs - 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD - 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis.
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Affiliation(s)
- Bruna de Oliveira Ascef
- Departamento de Medicina Preventiva, Faculdade de Medicina - FMUSP, Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 - 2º andar - sala 2214, São Paulo, SP, 01246-903, Brazil.
| | | | - Ana Cristina de Medeiros-Ribeiro
- Disciplina de Reumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, SP, Brazil
| | | | | | - Patrícia Coelho de Soárez
- Departamento de Medicina Preventiva, Faculdade de Medicina - FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil
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11
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Song YJ, Nam SW, Suh CH, Choe JY, Yoo DH. Biosimilars in the treatment of rheumatoid arthritis: a pharmacokinetic overview. Expert Opin Drug Metab Toxicol 2023; 19:751-768. [PMID: 37842948 DOI: 10.1080/17425255.2023.2270407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 10/10/2023] [Indexed: 10/17/2023]
Abstract
INTRODUCTION As of May 2023, 19 and 18 biosimilars have been approved for the treatment of rheumatoid arthritis (RA) by the European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) respectively. AREA COVERED Pharmacokinetic results of phase 1 studies of approved biosimilars were reviewed by systematic literature search. The impact of immunogenicity on the pharmacokinetic data and clinical response was assessed, and the potential benefit of monitoring serum concentrations of biologic drugs is discussed. The advantage of subcutaneous CT-P13 (an infliximab biosimilar) in clinical practice is reviewed. EXPERT OPINION Biosimilars are approved based on the totality of evidence including comparable physiochemical properties, PK / PD profiles, and clinical efficacy and safety to the originator. To utilize biosimilars more effectively, physicians should be aware of the utility of combination DMARD therapy to reduce immunogenicity and maintain efficacy and PK profile. PK monitoring, however, is not currently recommended in clinical practice. CT-P13 subcutaneous (SC) is the first SC infliximab used for treatment of RA patients. Based on data from clinical studies and the real world, SC-infliximab is an attractive therapeutic option compared to IV formulations of infliximab based on its efficacy, pharmacokinetics, patient-reported outcomes, and safety profile.
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Affiliation(s)
- Yeo-Jin Song
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
- Hanyang University Institute of Rheumatologic Research, Seoul, Republic of Korea
| | - Seoung Wan Nam
- Department of Rheumatology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Chang Hee Suh
- Department of Rheumatology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jung Yoon Choe
- Department of Rheumatology, Daegu Catholic University Medical Center, Daegu, Republic of Korea
| | - Dae Hyun Yoo
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
- Hanyang University Institute of Rheumatologic Research, Seoul, Republic of Korea
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12
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Ho Lee Y, Gyu Song G. Comparative efficacy and safety of tumor necrosis factor inhibitors and their biosimilars in patients with rheumatoid arthritis having an insufficient response to methotrexate : A network meta-analysis. Z Rheumatol 2023; 82:248-255. [PMID: 34223982 DOI: 10.1007/s00393-021-01041-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE This study aimed to compare the effectiveness and safety of tumor necrosis factor inhibitor (TNFI) biosimilars to TNFI originators in patients with active rheumatoid arthritis (RA) who responded inadequately to methotrexate (MTX). METHODS We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effectiveness and safety of TNFI biosimilars to TNFIs in patients with RA who had not responded adequately to MTX. RESULTS A total of 18 RCTs (8 adalimumab, 7 infliximab, and 3 etanercept) comprising 4039 patients randomized to TNFI biosimilars and 3905 to TNFI treatment were included. The American College of Rheumatology 20% improvement (ACR20) response rate was significantly higher for TNFI biosimilar-treated patients than for TNFI-treated patients (odds ratio, OR 1.140, 95% confidence interval, CI 1.031-1.261, P = 0.011); however, subgroup analysis by the TNFI type showed that the ACR20 response rates were not different among the biosimilars of adalimumab, infliximab, and etanercept compared with the originators. The ACR50 response rate was significantly higher for TNFI biosimilar-treated patients than for TNFI treated patients (OR 1.096, 95% CI 1.001-1.200, P = 0.047). Subgroup analysis by the TNFI type showed that the ACR50 response rates did not differ among the biosimilars of adalimumab and infliximab compared with the originators; however, the ACR50 response rate was significantly higher in etanercept biosimilar-treated patients than in etanercept-treated patients (OR 1.406, 95% CI 1.111-1.780, P = 0.005). No significant difference was observed between the TNFI biosimilars and TNFIs as per ACR70. There was no significant difference in the number of patients who experienced adverse events (AEs) between TNFI biosimilars and TNFIs (OR 0.961, 95% CI 0.876-1.055, P = 0.402); however, subgroup analysis by the TNFI type showed that the adalimumab biosimilar caused fewer AEs than adalimumab (OR 0.865, 95% CI 0.756-0.989, P = 0.034). Serious AEs and withdrawals due to AEs did not differ between TNFI biosimilars and TNFIs. CONCLUSION This meta-analysis showed that TNFI biosimilars had an overall comparable efficacy and safety profile compared with their originators in RA patients.
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Affiliation(s)
- Young Ho Lee
- Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, 02841, Seongbuk-gu, Seoul, Korea (Republic of).
| | - Gwan Gyu Song
- Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, 02841, Seongbuk-gu, Seoul, Korea (Republic of)
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13
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Martinez-Vinson C, Lemoine A, Bouhnik Y, Braithwaite B, Fohlen-Weill A, Addison J. PERFUSE: Non-Interventional Cohort Study of Patients Receiving Infliximab Biosimilar SB2: Results in Pediatric Patients. J Pediatr Gastroenterol Nutr 2023; 76:451-459. [PMID: 36729422 PMCID: PMC10013152 DOI: 10.1097/mpg.0000000000003683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 10/27/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVES PERFUSE is a non-interventional study of 1233 patients [inflammatory rheumatic disease, n = 496; inflammatory bowel disease (IBD), n = 737] receiving infliximab (IFX) biosimilar SB2 therapy. This analysis describes response to treatment and persistence on SB2 for up to 12 months in pediatric IBD patients (n = 126). METHODS Pediatric IBD patients with Crohn disease (CD) or ulcerative colitis (UC), either naïve or switched from originator IFX, who started SB2 in routine practice after September 2017 were eligible. Data were captured for 12 months following SB2 initiation. Disease activity was measured using C-reactive protein (CRP) levels and the Harvey-Bradshaw Index or Pediatric Ulcerative Colitis Activity Index for CD and UC patients, respectively. Body mass index and height z scores were used to assess patient growth between initiation (M0) and month 12 (M12). RESULTS One hundred twenty-six pediatric IBD patients were included (102 CD patients, 51 naïve and 51 switched; 24 UC patients, 9 naïve and 15 switched). Naive patients' disease scores decreased between M0 and M12. CRP measurements also decreased in naïve CD patients. Switched patients' disease scores and CRP levels remained stable between M0 and M12. Height z scores improved significantly over the course of the treatment for all groups except for naïve UC patients. CONCLUSIONS SB2 provides effective disease control for naïve and switched pediatric patients. Clinical remission rates improved in naïve patients and no loss of control was observed in switched patients after 1 year. Growth failure is not observed in IBD patients under SB2 treatment.
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Affiliation(s)
- Christine Martinez-Vinson
- From the Service de Gastroentérologie et Nutrition Pédiatriques, Hôpital Universitaire Robert-Debré, Paris, France
| | - Anaïs Lemoine
- the Service de Nutrition et Gastroentérologie Pédiatriques, Hôpital Trousseau, APHP, Sorbonne Université, Paris, France
| | - Yoram Bouhnik
- Paris IBD Center, Groupe Hospitalier Privé Ambroise Paré - Hartmann, Neuilly sur Seine, France
| | | | - Audrey Fohlen-Weill
- Biogen France SAS, Gastroenterology & Rhumatologie, Biosimilars, Paris, France
| | - Janet Addison
- Biogen IDEC, Clinical Research, Biosimilars, Maidenhead, UK
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Chi XK, Xu XL, Chen BY, Su J, Du YZ. Combining nanotechnology with monoclonal antibody drugs for rheumatoid arthritis treatments. J Nanobiotechnology 2023; 21:105. [PMID: 36964609 PMCID: PMC10039584 DOI: 10.1186/s12951-023-01857-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/15/2023] [Indexed: 03/26/2023] Open
Abstract
Rheumatoid arthritis (RA) is a systemic immune disease characterized by synovial inflammation. Patients with RA commonly experience significant damage to their hand and foot joints, which can lead to joint deformities and even disability. Traditional treatments have several clinical drawbacks, including unclear pharmacological mechanisms and serious side effects. However, the emergence of antibody drugs offers a promising approach to overcome these limitations by specifically targeting interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and other cytokines that are closely related to the onset of RA. This approach reduces the incidence of adverse effects and contributes to significant therapeutic outcomes. Furthermore, combining these antibody drugs with drug delivery nanosystems (DDSs) can improve their tissue accumulation and bioavailability.Herein, we provide a summary of the pathogenesis of RA, the available antibody drugs and DDSs that improve the efficacy of these drugs. However, several challenges need to be addressed in their clinical applications, including patient compliance, stability, immunogenicity, immunosupression, target and synergistic effects. We propose strategies to overcome these limitations. In summary, we are optimistic about the prospects of treating RA with antibody drugs, given their specific targeting mechanisms and the potential benefits of combining them with DDSs.
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Affiliation(s)
- Xiao-Kai Chi
- College of Pharmacy, Jiamusi University, 258 Xuefu Road, Jiamusi, 154007, China
- Shulan International Medical College, Zhejiang Shuren University), 8 Shuren Street, Hangzhou, 310015, China
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou, 310058, China
| | - Xiao-Ling Xu
- Shulan International Medical College, Zhejiang Shuren University), 8 Shuren Street, Hangzhou, 310015, China.
| | - Bang-Yao Chen
- Shulan International Medical College, Zhejiang Shuren University), 8 Shuren Street, Hangzhou, 310015, China
| | - Jin Su
- College of Pharmacy, Jiamusi University, 258 Xuefu Road, Jiamusi, 154007, China.
| | - Yong-Zhong Du
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou, 310058, China.
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Ye H, Liu S, Xu J, Chai K, He D, Fang Y, Xie Q, Liu H, Liu Y, Hua B, Hu J, Zhang Z, Zhou M, Zhao D, Li Y, Jiang Z, Wang M, Li J, Zhang Z, Li X, Li Y, Sun E, Bi L, Wei W, Tie N, He L, Huang X, Zhang Y, Huang Q, Wang X, Liu X, Li J, Su Y. Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study. Rheumatol Ther 2023; 10:757-773. [PMID: 36964872 PMCID: PMC10140208 DOI: 10.1007/s40744-023-00544-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 02/20/2023] [Indexed: 03/26/2023] Open
Abstract
OBJECTIVES The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. METHODS We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than - 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. RESULTS In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were - 4.6% and the lower limit of one-sided 97.5% confidence interval was - 14.29%, not less than the lower limit of the non-inferiority margin (- 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference - 4.6%, 95% CI - 14.29% to 5.12%) and PPS (difference - 3.3%, 95% CI - 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. CONCLUSIONS Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. TRIAL REGISTRATION NUMBER NCT03478111.
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Affiliation(s)
- Hua Ye
- Rheumatology Department, Peking University People's Hospital, No. 11, XiZhimen South Street, Beijing, 100044, China
| | - Shengyun Liu
- Rheumatology and Immunology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jian Xu
- Rheumatology and Immunology Department, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Kexia Chai
- Rheumatology and Immunology Department, Qinghai University Affiliated Hospital, Xining, China
| | - Dongyi He
- Arthrology Department, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
| | - Yongfei Fang
- Rheumatology and Immunology Department of Traditional Chinese Medicine, The Southwest Hospital of Army Medical University, Chongqing, China
| | - Qibing Xie
- Rheumatology and Immunology Department, West China Hospital Sichuan University, Chengdu, China
| | - Huaxiang Liu
- Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, China
| | - Ying Liu
- Rheumatology and Immunology Department of Traditional Chinese Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Bingzhu Hua
- Rheumatology and Immunology Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jiankang Hu
- Rheumatology and Immunology Department, Pingxiang People's Hospital, Pingxiang, China
| | - Zhiyi Zhang
- Rheumatology and Immunology Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mingxuan Zhou
- Immunology Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Dongbao Zhao
- Rheumatology and Immunology Department, Changhai Hospital of Shanghai, Shanghai, China
| | - Yan Li
- Rheumatology and Immunology Department, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Zhenyu Jiang
- Rheumatology and Immunology Department, The First Hospital of Jilin University, Changchun, China
| | - Meimei Wang
- Rheumatology and Immunology Department, Zhongda Hospital Southeast University, Nanjing, China
| | - Jingyang Li
- Rheumatology and Immunology Department, Zhuzhou Central Hospital, Zhuzhou, China
| | - Zhuoli Zhang
- Rheumatology and Immunology Department, Peking University First Hospital, Beijing, China
| | - Xiaomei Li
- Rheumatology and Immunology Department, Anhui Provincial Hospital, Hefei, China
| | - Yang Li
- Rheumatology and Immunology Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Erwei Sun
- Rheumatology and Immunology Department, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Liqi Bi
- Rheumatology and Immunology Department, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Wei Wei
- Rheumatology and Immunology Department, Tianjin Medical University General Hospital, Tianjin, China
| | - Ning Tie
- Rheumatology and Immunology Department, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot City, China
| | - Lan He
- Rheumatology and Immunology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiangyang Huang
- Rheumatology and Immunology Department, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yan Zhang
- Rheumatology and Immunology Department, The Second Affiliated Hospital, Tangdu Hospital The Air Force Military Medical University, Xi'an, China
| | - Qingchun Huang
- Rheumatology Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Xiaofei Wang
- Rheumatology and Immunology Department, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiangyuan Liu
- Rheumatology and Immunology Department, Peking University Third Hospital, Beijing, China
| | - Jing Li
- Mabpharm Limited, Taizhou, China
| | - Yin Su
- Rheumatology Department, Peking University People's Hospital, No. 11, XiZhimen South Street, Beijing, 100044, China.
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16
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Lee YH, Song GG. Comparative efficacy and safety of infliximab and its biosimilars in patients with rheumatoid arthritis presenting an insufficient response to methotrexate : A network meta-analysis. Z Rheumatol 2023; 82:114-122. [PMID: 34228181 DOI: 10.1007/s00393-021-01040-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To assess the relative efficacy and safety of infliximab and its biosimilars in patients with active rheumatoid arthritis (RA) who showed an inadequate response to methotrexate (MTX). METHODS We performed a Bayesian network meta-analysis combining direct and indirect evidence from randomized controlled trials (RCTs), comparing the efficacy and safety of infliximab biosimilars versus the originator product in patients with active RA despite receiving MTX. RESULTS Overall, 7 RCTs involving 3168 patients, including 7 biologic agents, met the inclusion criteria. The NI-071 was listed at the top left of the diagonal of the league table because it was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the American College of Rheumatology 20 (ACR20) response rate. SB2 was listed at the bottom right of the diagonal of the league table because it was associated with the least favorable results. Based on SUCRA, NI-071 had the highest probability of being the best treatment agent in terms of the ACR20 response rate (SUCRA = 0.731), followed by ABP 710, CT-P13, BCD-055, infliximab, Exemptia, PF-06438179, and SB2 (SUCRA = 0.311). Although statistically non-significant differences in safety ranking were observed for serious adverse events (SAEs) among the treatment options, ABP 710 presented the highest safety probability (SUCRA = 0.739) while BCD-055 showed the lowest safety profile (SUCRA = 0.289). CONCLUSION No significant difference in ACR20 response rates and SAEs were detected between infliximab biosimilars and the originator in the investigated study populations.
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Affiliation(s)
- Young Ho Lee
- Division of Rheumatology, Department of Internal Medicine, Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of).
| | - Gwan Gyu Song
- Division of Rheumatology, Department of Internal Medicine, Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of)
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Kim DW, Lee Y, Kim G, Kim SH, Cho DH, Choi J, Kwon YH, Park Y, Choi W, Park DI. Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea. Adv Ther 2023; 40:1047-1061. [PMID: 36624354 PMCID: PMC9989004 DOI: 10.1007/s12325-022-02404-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 12/07/2022] [Indexed: 01/11/2023]
Abstract
INTRODUCTION SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.
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Affiliation(s)
- Dong W Kim
- Division of Rheumatology, Department of Internal Medicine, Inje University, Busan Paik Hospital, Busan, Korea
| | - Yousun Lee
- Division of Rheumatology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Geuntae Kim
- Division of Rheumatology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
| | - Sang H Kim
- Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - Dae H Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Jeongmin Choi
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Nowon-gu, Korea
| | - Yong H Kwon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Younjin Park
- Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
| | - Wooree Choi
- Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
| | - Dong I Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Koh SJ, Hong SN, Park SK, Ye BD, Kim KO, Shin JE, Yoon YS, Lee HS, Jung SH, Choi M, Na SY, Choi CH, Kim JS. Korean clinical practice guidelines on biologics for moderate to severe Crohn's disease. Intest Res 2023; 21:43-60. [PMID: 36245343 PMCID: PMC9911268 DOI: 10.5217/ir.2022.00029] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 04/18/2022] [Indexed: 11/05/2022] Open
Abstract
Crohn's disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.
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Affiliation(s)
- Seong-Joon Koh
- Department of Internal Medicine, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo-Kyung Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Yong Sik Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hong Sub Lee
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Sung Hoon Jung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Miyoung Choi
- National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Soo-Young Na
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea,Correspondence to Joo Sung Kim, Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel: +82-2-740-8112, Fax: +82-2-743-6701, E-mail:
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Na SY, Choi CH, Song EM, Bang KB, Park SH, Kim ES, Park JJ, Keum B, Lee CK, Lee BI, Ryoo SB, Koh SJ, Choi M, Kim JS. Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis. Intest Res 2023; 21:61-87. [PMID: 35645321 PMCID: PMC9911265 DOI: 10.5217/ir.2022.00007] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 03/07/2022] [Indexed: 02/09/2023] Open
Abstract
Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.
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Affiliation(s)
- Soo-Young Na
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea,Correspondence to Chang Hwan Choi, Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea. Tel: +82-2-6299-1418, Fax: +82-2-6299-2064, E-mail:
| | - Eun Mi Song
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Ki Bae Bang
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Jun Park
- Department of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Bora Keum
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chang Kyun Lee
- Department of Gastroenterology, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Bo-In Lee
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Fautrel B, Bouhnik Y, Dieude P, Richette P, Dougados M, Freudensprung U, Brigui A, Addison J. Real-world evidence of the use of the infliximab biosimilar SB2: data from the PERFUSE study. Rheumatol Adv Pract 2023; 7:rkad031. [PMID: 37122809 PMCID: PMC10130189 DOI: 10.1093/rap/rkad031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 03/10/2023] [Indexed: 05/02/2023] Open
Abstract
Objective PERFUSE is a non-interventional study of 1233 adult patients (rheumatology, n = 496; IBD, n = 737) receiving routine infliximab (IFX) biosimilar SB2 therapy. The aim of this report was to investigate the 12-month persistence, effectiveness and safety outcomes of routine SB2 treatment in patients with chronic inflammatory rheumatic disease. Methods Patients with a diagnosis of RA, PsA or axial spondyloarthritis (axSpA) were assigned to one of three study cohorts according to whether SB2 treatment initiated after September 2017 had been the first IFX treatment (IFX naïve) or followed transition from reference IFX (IFX ref) or another IFX biosimilar (IFX bs). Outcomes to month 12 (±2) included persistence (primary outcome), SB2 dose, disease status, immunogenicity and safety. Results At month 12, persistence on SB2 in IFX-naïve, IFX ref and IFX bs cohorts, respectively, [mean percentage (95% CI)] by indication was as follows: 59% (36.1, 76.2), 75% (57.5, 86.1) and 85% (69.6, 93.0) for RA (n = 98); 64% (34.3, 83.3), 87% (65.6, 95.7) and 83% (60.0, 93.1) for PsA (n = 62); and 56% (44.4, 66.5), 80% (70.8, 86.1) and 80% (72.5, 85.6) for axSpA (n = 336). Disease activity was comparable at baseline and month 12 within the IFX ref and bs subgroups of all cohorts by indication. No immunogenicity concerns or new safety signals were detected. Conclusion SB2 was safe and effective in IFX-naïve patients and in patients transitioned from prior IFX ref or bs. Trial registration clinicaltrials.gov, NCT03662919.
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Affiliation(s)
- Bruno Fautrel
- Correspondence to Bruno Fautrel, Rheumatology Department, Sorbonne University, AP-HP, Pitié-Salpêtrière Hospital, 47–83 boulevard de l'Hôpital, 75013 Paris, France.
| | - Yoram Bouhnik
- Paris IBD Center, Groupe Hospitalier Privé Ambroise Paré—Hartmann, Neuilly-sur-Seine, France
| | - Philippe Dieude
- Department of Rheumatology, Paris-Cité University, AP-HP, Paris, France
- Hôpital Bichat-Claude Bernard, INSERM UMR1152, Paris, France
| | - Pascal Richette
- Rheumatology Department, Hôpital Lariboisière, AP-HP, Paris, France
| | - Maxime Dougados
- Department of Rheumatology, Paris-Cité University, Hôpital Cochin, AP-HP, Paris, France
- Clinical Epidemiology and Biostatistics, INSERM (U1153): PRES Sorbonne Paris-Cité, Paris, France
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21
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Bouhnik Y, Fautrel B, Beaugerie L, Pelletier AL, Martinez-Vinson C, Freudensprung U, Brigui A, Addison J. PERFUSE: a French non-interventional study of patients with inflammatory bowel disease receiving infliximab biosimilar SB2: a 12-month analysis. Therap Adv Gastroenterol 2023; 16:17562848221145654. [PMID: 36936799 PMCID: PMC10021102 DOI: 10.1177/17562848221145654] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 11/28/2022] [Indexed: 03/21/2023] Open
Abstract
Background FlixabiTM (SB2) is a biosimilar of the reference infliximab (IFX), Remicade®. Published evidence on long-term, real-world use of SB2 in patients either IFX naive or transitioned from prior IFX is scarce. Objectives We evaluated persistence, effectiveness, and safety of SB2 over 12 months in adults with IBD [Crohn's disease (CD) and ulcerative colitis (UC)], participating in PERFUSE. Design PERFUSE is a long-term, non-interventional, multicenter study of patients receiving SB2 at specialist sites across France. Methods SB2 treatment was initiated in September 2017, either as first IFX treatment (IFX naive), after transition from treatment with reference IFX (IFX ref) or another IFX biosimilar (IFX bs), or both IFX ref and IFX bs (IFX multiswitch). Outcomes up to Month 12 (±2) include persistence on SB2 (primary outcome measure), SB2 dose, disease status, immunogenicity, and safety. Results This final 12-month analysis of patients with IBD includes 569 with CD and 168 with UC. Persistence [95% confidence interval (CI)] at Month 12 was CD: 89% (77.2; 94.9), UC: 78.5% (58.2; 89.8) for IFX naive; CD: 94% (91.0; 96.1), UC: 92.8% (84.8; 96.7) for IFX ref; CD: 91.6% (86.0; 95.0), UC: 94.2% (83.1; 98.1) for IFX bs; and CD 100% (100; 100), UC 100% (100; 100) for IFX multiswitch. In the CD and UC cohorts, disease activity among IFX naive patients declined from baseline to Month 12; with any prior IFX, the proportions of patients in remission at baseline, Month 6, and Month 12 remained unchanged in the UC cohort, and were comparable or higher in the CD cohort. No immunogenicity or safety signals were detected. Conclusions Patients with IBD can be initiated on SB2 or transitioned from IFX ref and/or IFX bs to SB2, with no loss of disease control or safety concerns, with >75% of naive and >90% of transitioned patients continuing on SB2 treatment at 12 months.
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Affiliation(s)
| | - Bruno Fautrel
- Rheumatology Department, Pitié-Salpêtrière
Hospital, Sorbonne University, AP-HP, Paris, France
- Sorbonne University – INSERM UMRS 1136, Pierre
Louis Institute for Epidemiology and Public Health, Paris, France
| | - Laurent Beaugerie
- Sorbonne University – INSERM UMRS 1136, Pierre
Louis Institute for Epidemiology and Public Health, Paris, France
- Hôpital Saint-Antoine, AP-HP, Paris,
France
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22
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Murayama MA, Shimizu J, Miyabe C, Yudo K, Miyabe Y. Chemokines and chemokine receptors as promising targets in rheumatoid arthritis. Front Immunol 2023; 14:1100869. [PMID: 36860872 PMCID: PMC9968812 DOI: 10.3389/fimmu.2023.1100869] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 01/31/2023] [Indexed: 02/16/2023] Open
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease that commonly causes inflammation and bone destruction in multiple joints. Inflammatory cytokines, such as IL-6 and TNF-α, play important roles in RA development and pathogenesis. Biological therapies targeting these cytokines have revolutionized RA therapy. However, approximately 50% of the patients are non-responders to these therapies. Therefore, there is an ongoing need to identify new therapeutic targets and therapies for patients with RA. In this review, we focus on the pathogenic roles of chemokines and their G-protein-coupled receptors (GPCRs) in RA. Inflamed tissues in RA, such as the synovium, highly express various chemokines to promote leukocyte migration, tightly controlled by chemokine ligand-receptor interactions. Because the inhibition of these signaling pathways results in inflammatory response regulation, chemokines and their receptors could be promising targets for RA therapy. The blockade of various chemokines and/or their receptors has yielded prospective results in preclinical trials using animal models of inflammatory arthritis. However, some of these strategies have failed in clinical trials. Nonetheless, some blockades showed promising results in early-phase clinical trials, suggesting that chemokine ligand-receptor interactions remain a promising therapeutic target for RA and other autoimmune diseases.
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Affiliation(s)
- Masanori A Murayama
- Department of Animal Models for Human Diseases, Institute of Biomedical Science, Kansai Medical University, Osaka, Japan
| | - Jun Shimizu
- Department of Immunology and Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Chie Miyabe
- Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Kazuo Yudo
- Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Yoshishige Miyabe
- Department of Immunology and Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
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Srimadh Bhagavatham SK, Pulukool SK, Pradhan SS, R S, Ashok Naik A, V M DD, Sivaramakrishnan V. Systems biology approach delineates critical pathways associated with disease progression in rheumatoid arthritis. J Biomol Struct Dyn 2022:1-22. [PMID: 36047508 DOI: 10.1080/07391102.2022.2115555] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease leading to inflammation, cartilage cell death, synoviocyte proliferation, and increased and impaired differentiation of osteoclasts and osteoblasts leading to joint erosions and deformities. Transcriptomics, proteomics, and metabolomics datasets were analyzed to identify the critical pathways that drive the RA pathophysiology. Single nucleotide polymorphisms (SNPs) associated with RA were analyzed for the functional implications, clinical outcomes, and blood parameters later validated by literature. SNPs associated with RA were grouped into pathways that drive the immune response and cytokine production. Further gene set enrichment analysis (GSEA) was performed on gene expression omnibus (GEO) data sets of peripheral blood mononuclear cells (PBMCs), synovial macrophages, and synovial biopsies from RA patients showed enrichment of Th1, Th2, Th17 differentiation, viral and bacterial infections, metabolic signalling and immunological pathways with potential implications for RA. The proteomics data analysis presented pathways with genes involved in immunological signaling and metabolic pathways, including vitamin B12 and folate metabolism. Metabolomics datasets analysis showed significant pathways like amino-acyl tRNA biosynthesis, metabolism of amino acids (arginine, alanine aspartate, glutamate, glutamine, phenylalanine, and tryptophan), and nucleotide metabolism. Furthermore, our commonality analysis of multi-omics datasets identified common pathways with potential implications for joint remodeling in RA. Disease-modifying anti-rheumatic drugs (DMARDs) and biologics treatments were found to modulate many of the pathways that were deregulated in RA. Overall, our analysis identified molecular signatures associated with the observed symptoms, joint erosions, potential biomarkers, and therapeutic targets in RA. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
| | - Sujith Kumar Pulukool
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India
| | - Sai Sanwid Pradhan
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India
| | - Saiswaroop R
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India
| | - Ashwin Ashok Naik
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India
| | - Datta Darshan V M
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India
| | - Venketesh Sivaramakrishnan
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India
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Ben Mrid R, Bouchmaa N, Ainani H, El Fatimy R, Malka G, Mazini L. Anti-rheumatoid drugs advancements: New insights into the molecular treatment of rheumatoid arthritis. Biomed Pharmacother 2022; 151:113126. [PMID: 35643074 DOI: 10.1016/j.biopha.2022.113126] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/13/2022] [Accepted: 05/13/2022] [Indexed: 11/02/2022] Open
Abstract
Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Significant improvement has been noted in the last two decades revealing the mechanisms of the development of RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and highlight the recent findings concerning the different classes of RA therapies including the conventional and modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target against inflammation, cartilage damage, and reduce side effects in arthritis.
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Affiliation(s)
- Reda Ben Mrid
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Najat Bouchmaa
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Hassan Ainani
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Rachid El Fatimy
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Gabriel Malka
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
| | - Loubna Mazini
- Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco.
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van Adrichem RCS, Voorneveld HJE, Waverijn GJ, Kok MR, Bisoendial RJ. The Non-medical Switch from Reference Adalimumab to Biosimilar Adalimumab is Highly Successful in a Large Cohort of Patients with Stable Inflammatory Rheumatic Joint Diseases: A Real-Life Observational Study. Rheumatol Ther 2022; 9:1109-1118. [PMID: 35655028 PMCID: PMC9314483 DOI: 10.1007/s40744-022-00465-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 05/11/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction The adalimumab biosimilar (ADAbio) Amgevita® has a similar efficacy and safety profile as the adalimumab reference (ADA) Humira®. We studied the clinical consequences of a non-medical switch from ADA to ADAbio in adult patients with mainly established rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA). Methods Patients that received treatment with ADA for at least three months were switched to ADAbio. Data was collected retrospectively from 1 year before the switch up to 6 months after. Results A total of 603 patients were switched from ADA to ADAbio (switch group). During a 1-year follow-up, over 93% of all patients underwent a successful transition in terms of disease activity and safety from ADA to biosimilar, supporting the bioequivalence of both drugs in patients with stable inflammatory rheumatic joint diseases. Forty patients (6.6%) switched back to ADA (re-switch group). There were no objective changes in disease activity score in 28 joints using C-reactive protein (DAS28-CRP), or adverse effects before and after the switch between both groups. Conclusions In line with earlier reports, the transition to ADAbio went successful in the majority of patients with stable inflammatory rheumatic joint diseases. Patient-reported symptoms without objective signs that indicate a flare of disease activity after the switch to ADAbio are probably explained by nocebo effects. A pre-emptive approach to counteract nocebo effects and stimulate placebo response may have a positive impact on health outcomes for patients and preserve the economic benefits of cost savings that can be achieved by prescribing a biosimilar instead of the reference drug.
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Affiliation(s)
- Roxanne C S van Adrichem
- Department of Rheumatology, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands.
| | - Hanneke J E Voorneveld
- Department of Rheumatology, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands
| | - Geeke J Waverijn
- Department of Rheumatology, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands
| | - Marc R Kok
- Department of Rheumatology, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands
| | - Radjesh J Bisoendial
- Department of Rheumatology, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands
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Venetsanopoulou AI, Voulgari PV, Drosos AA. Janus kinase versus TNF inhibitors: where we stand today in rheumatoid arthritis. Expert Rev Clin Immunol 2022; 18:485-493. [PMID: 35535405 DOI: 10.1080/1744666x.2022.2064275] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION In recent decades, Rheumatoid arthritis (RA) treatment landscape has evolved with the induction of new biological and targeted therapies that provide significant therapeutic benefits in patients with sustained disease. AREAS COVERED Tumor necrosis factor inhibitors (TNFi) were the first biologics used in the treatment of RA. Although they present a significant efficacy, an insufficient response of some patients led to further research and discovery of targeted therapies, such as Janus kinase inhibitors (JAKi), which act at a molecular level, regulating many cytokines. Clinical benefits have been seen with both TNFi and JAKi as monotherapy and combined with conventional synthetic disease-modifying antirheumatic drugs. Still, some significant side effects have been reported with JAKi, and several questions remain about their safety and selectivity in action. This review summarizes the current knowledge on the mechanism of action, the clinical efficacy, and safety of TNFi vs. JAKi. EXPERT OPINION TNFi and JAKi are particularly useful in treating inflammatory arthropathies. Both drug categories are recommended by ACR and EULAR institutions in RA patients suffering from moderate to severe disease. Safety data in long-term studies are required to determine the optimal benefit to the risk profile of JAKi use.
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Affiliation(s)
- Aliki I Venetsanopoulou
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Paraskevi V Voulgari
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Alexandros A Drosos
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
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Hanzel J, Jansen JM, ter Steege RWF, Gecse KB, D’Haens GR. Multiple Switches From the Originator Infliximab to Biosimilars Is Effective and Safe in Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study. Inflamm Bowel Dis 2022; 28:495-501. [PMID: 34013959 PMCID: PMC8972297 DOI: 10.1093/ibd/izab099] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Though a single nonmedical switch from the originator infliximab (IFX) to a biosimilar is considered effective and safe for most patients with inflammatory bowel disease (IBD), very limited data are available on multiple successive switches. METHODS We performed a prospective multicenter cohort study of adult IBD patients who underwent 2 switches from the originator IFX to CT-P13 to SB2 (group 1), 1 switch from CT-P13 to SB2 (group 2), and 1 switch from the originator IFX to CT-P13 (group 3). Patients were assessed at 4 and 12 months since the most recent switch for remission using clinical (physician's assessment) and biochemical (C-reactive protein [CRP], and fecal calprotectin [FC]) measures. Patients discontinuing treatment for ineffectiveness or adverse events before month 12 were imputed as nonremitters. RESULTS One hundred seventy-six patients (Crohn's disease 71%, ulcerative colitis 27.8%, IBD unclassified 1.2%; group 1, 69; group 2, 80; group 3, 27) were included. At 12 months after the most recent switch 76.9% (40 of 52, group 1), 65.7% (46 of 70, group 2) and 76.9% (20 of 26, group 3) of patients were in clinical remission. Treatment persistence at 12 months was 85.0%, 87.0%, and 70.1%, respectively. There were no significant differences in the rate of clinical, CRP, FC remission, or treatment persistence at 12 months between the 3 groups. Infusion reactions occurred in 1.7% of patients (3/176), all in patients with antidrug antibodies from group 2. CONCLUSIONS Multiple successive switching and switching between biosimilars of IFX seemed to be effective and safe.
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Affiliation(s)
- Jurij Hanzel
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, the Netherlands
- Medical Faculty, University of Ljubljana, Department of Gastroenterology, UMC Ljubljana, Ljubljana, Slovenia
| | - Jeroen M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
| | - Rinze W F ter Steege
- Department of Gastroenterology and Hepatology, Martini Ziekenhuis, Groningen, the Netherlands
| | - Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, the Netherlands
| | - Geert R D’Haens
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, the Netherlands
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Hariprasad SM, Gale RP, Weng CY, Ebbers HC, Rezk MF, Tadayoni R. An Introduction to Biosimilars for the Treatment of Retinal Diseases: A Narrative Review. Ophthalmol Ther 2022; 11:959-982. [PMID: 35278204 PMCID: PMC9114261 DOI: 10.1007/s40123-022-00488-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 02/16/2022] [Indexed: 12/03/2022] Open
Abstract
Biological therapies have revolutionized the treatment of disease across a number of therapeutic areas including retinal diseases. However, on occasion, such treatments may be relatively more expensive compared to small molecule therapies. This can restrict patient access and treatment length leading to suboptimal clinical outcomes. Several biosimilar candidates of ranibizumab and aflibercept are currently in development and the first biosimilar of ranibizumab received EMA approval in August and FDA approval in September 2021. Biosimilars are biological medicines that are highly similar to an already-approved biological medicine (reference product). The physicochemical and clinical similarity of a biosimilar is determined by a rigorous analytical and clinical program, including extensive pharmacokinetic and pharmacodynamic analysis with phase III equivalence studies where appropriate. These phase III studies are carried out in a patient population that is representative of all of the potential approved therapeutic indications of the originator product and the most sensitive for detecting potential differences between the biosimilar and the reference product. Biosimilars have been used successfully across a wide range of therapeutic areas for the past 15 years where they have achieved substantial cost savings that can be reinvested into healthcare systems without affecting the quality of patient care. The current review provides an introduction to biosimilars with the aim of preparing retinal specialists for discussing these products with their patients.
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Affiliation(s)
- Seenu M Hariprasad
- Department of Ophthalmology and Visual Science, University of Chicago Medicine, Chicago, IL, USA.
| | - Richard P Gale
- Department of Ophthalmology, York Teaching Hospital, University of York, York, UK
| | - Christina Y Weng
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA
| | | | | | - Ramin Tadayoni
- Université de Paris, AP-HP, Lariboisière, Saint Louis and Fondation Adolphe de Rothschild Hospitals, Paris, France
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29
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Tanaka E, Kawahito Y, Kohno M, Hirata S, Kishimoto M, Kaneko Y, Tamai H, Seto Y, Morinobu A, Sugihara T, Murashima A, Kojima M, Mori M, Ito H, Kojima T, Sobue Y, Nishida K, Matsushita I, Nakayama T, Yamanaka H, Harigai M. Systematic review and meta-analysis of biosimilar for the treatment of rheumatoid arthritis informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis. Mod Rheumatol 2022; 32:74-86. [PMID: 33706664 DOI: 10.1080/14397595.2021.1899591] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 03/01/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To evaluate the efficacy and safety of biosimilars compared with reference biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as a part of the process of developing the 2020 update of the Japan College of Rheumatology guidelines for the management of RA. METHODS PubMed, Cochrane Library, and Japan Centra Revuo Medicina were searched for articles to conduct a systematic review (SR). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS Twenty randomized controlled trials were included (biosimilars of infliximab, etanercept, and adalimumab). A meta-analysis revealed that the risk ratios (RRs) and 95% confidence intervals (CIs) of achieving the American College of Rheumatology 50% response (ACR50) at week 24 and serious adverse events (SAEs) for biosimilars compared with the reference bDMARDs were 1.04 (0.98-1.10) and 0.84 (0.61-1.18), respectively. The RRs of achieving ACR50 and SAEs at week 24 were respectively 0.93 (0.69-1.26) and 2.15 (0.55-8.35) in the patients who switched to biosimilars from the reference bDMARDs and 0.92 (0.76-1.12) and 1.41 (0.32-6.15) in those who continued the reference bDMARDs. CONCLUSION Biosimilars and reference bDMARDs were equally useful for the management of RA.
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Affiliation(s)
- Eiichi Tanaka
- Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Yutaka Kawahito
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masataka Kohno
- Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shintaro Hirata
- Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan
| | - Mitsumasa Kishimoto
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hiroya Tamai
- Department of Rheumatology, Yachiyo Medical Center, Tokyo Women's Medical University, Chiba, Japan
| | - Yohei Seto
- Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Akio Morinobu
- Department of Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takahiko Sugihara
- Division of Maternal Medicine, Center for Maternal-Fetal, Neonatal and Reproductive Medicine/Japan Drug Information Institute in Pregnancy, National Center for Child Health and Development, Tokyo, Japan
| | - Atsuko Murashima
- Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Aichi, Japan
| | - Masayo Kojima
- Department of Advanced Medicine for Rheumatic Diseases and Orthopedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masaaki Mori
- Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiromu Ito
- Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Toshihisa Kojima
- Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Yasumori Sobue
- Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
- Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama, Japan
| | - Keiichiro Nishida
- Department of Rehabilitation Medicine, Kanazawa Medical University, Ishikawa, Japan
| | - Isao Matsushita
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | | | - Hisashi Yamanaka
- Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
- Rheumatology, Sanno Medical Center, Tokyo, Japan
- Department of Rheumatology, International University of Health and Welfare, Tokyo, Japan
| | - Masayoshi Harigai
- Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
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30
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Liu Y, Liu S, Liu L, Gong X, Liu J, Sun L, Liu X, Wu L, Chen L, Wang L, Luo L, Lin J, Tie N, Jiang Z, Wu J, Lu F, Sun H, Li X, Yang N, Chai K, Wei H, Da Z, Zhao C, Dai L, Wang Y, Shi G, Zhang Z, Song H, Guo Q, Liu YC, Li Z. Fine Comparison of the Efficacy and Safety Between GB242 and Infliximab in Patients with Rheumatoid Arthritis: A Phase III Study. Rheumatol Ther 2021; 9:175-189. [PMID: 34806155 PMCID: PMC8814292 DOI: 10.1007/s40744-021-00396-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/01/2021] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. METHODS Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. RESULTS A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. CONCLUSIONS GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.
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Affiliation(s)
- Yanying Liu
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
- Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shengyun Liu
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lin Liu
- Department of Rheumatology and Immunology, Xuzhou General Hospital, Xuzhou, China
| | - Xiaowei Gong
- Department of Rheumatology, The First Hospital of Qiqihar, Qiqihar, China
| | - Ju Liu
- Department of Rheumatology and Immunology, Jiujiang No. 1 People's Hospital, Jiujiang, China
| | - Lingyun Sun
- Department of Rheumatology and Immunology, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiumei Liu
- Department of Rheumatology and Immunology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Lijun Wu
- Department of Rheumatology and Immunology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Linjie Chen
- Department of Rheumatology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Ling Wang
- Department of Rheumatology and Immunology, Zaozhuang Municipal Hospital, Zaozhuang, China
| | - Li Luo
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jinying Lin
- Department of Rheumatology and Immunology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Ning Tie
- Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia University, Hohhot, China
| | - Zhenyu Jiang
- Department of Rheumatology, First Hospital of Jilin University, Bethune, Changchun, China
| | - Jian Wu
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fuai Lu
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Hongsheng Sun
- Department of Rheumatology and Immunology, Shandong Province Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiaomei Li
- Department of Rheumatology and Immunology, Anhui Provincial Hospital, Hefei, China
| | - Niansheng Yang
- Department of Rheumatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Kexia Chai
- Department of Hematology and Rheumatology, Qinghai University Affiliated Hospital, Xining, China
| | - Hua Wei
- Department of Rheumatology and Immunology, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Zhanyun Da
- Department of Rheumatology and Immunology, Affiliated Hospital of Nantong University, Nantong, China
| | - Cheng Zhao
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lie Dai
- Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Youlian Wang
- Department of Rheumatology and Immunology, Jiangxi Province People's Hospital, Nanchang, China
| | - Guixiu Shi
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Zhenchun Zhang
- Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, China
| | - Hui Song
- Department of Rheumatology and Immunology, Beijing Jishuitan Hospital, Beijing, China
| | - Qian Guo
- Department of Medical Affairs, Genor Biopharma Co., Ltd., Shanghai, China
| | - Yingxue Cathy Liu
- Department of Biometrics, Genor Biopharma Co., Ltd., Shanghai, China
| | - Zhanguo Li
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
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Mazza S, Piazza O Sed N, Conforti FS, Fascì A, Rimondi A, Marinoni B, Casini V, Ricci C, Munari F, Pirola L, Invernizzi P, Girelli C, Lupinacci G, Pastorelli L, Cavallaro F, Ferraris L, Colucci A, Amato A, Eugenio Tontini G, Vecchi M, Fiorino G, Caprioli F. Safety and clinical efficacy of the double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicenter cohort study. Clin Transl Sci 2021; 15:172-181. [PMID: 34523800 PMCID: PMC8742653 DOI: 10.1111/cts.13131] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/17/2021] [Accepted: 07/19/2021] [Indexed: 12/14/2022] Open
Abstract
Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT‐P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX‐double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single‐switched from originator IFX to CT‐P13 was performed, before and after an inverse probability of treatment weighting (IPTW)‐based propensity score analysis. Fifty‐two double‐switched patients with IBD were enrolled. The 24‐ and 52‐week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval [CI] 94%–100%) and 90% (95% CI 81%–99%), respectively. Four patients experienced a total of five AEs, all graded 1–3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24‐week and follow‐up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double‐switch group with a single‐switch group of 66 patients with IBD; all these results were confirmed by IPTW‐adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT‐P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications.
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Affiliation(s)
- Stefano Mazza
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy
| | - Nicole Piazza O Sed
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy
| | - Francesco Simone Conforti
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy
| | - Alberto Fascì
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Alessandro Rimondi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Beatrice Marinoni
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | | | - Chiara Ricci
- Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili, Brescia, Italy
| | | | - Lorena Pirola
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Carlo Girelli
- Gastroenterology and Digestive Endoscopy Unit, Busto Arsizio Hospital, Varese, Italy
| | - Guido Lupinacci
- Gastroenterology and Endoscopy Unit, Ospedale Maggiore, Crema, Italy
| | - Luca Pastorelli
- Gastroenterology and Liver Unit, ASST Santi Paolo e Carlo, Ospedale San Paolo Milan, Italy.,Department of Health Sciences, Univeristà degli Studi di Milano, Milan, Italy
| | - Flaminia Cavallaro
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy
| | - Luca Ferraris
- Gastroenterology and Endoscopy Unit, Gallarate Hospital, Varese, Italy
| | - Alice Colucci
- Gastroenterology and Endoscopy Unit, Gallarate Hospital, Varese, Italy
| | - Arnaldo Amato
- Gastroenterology and Digestive Endoscopy Unit, Valduce Hospital, Como, Italy
| | - Gian Eugenio Tontini
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Maurizio Vecchi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Gionata Fiorino
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Flavio Caprioli
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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32
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Lopez L, Griffier R, Barnetche T, Lhomme E, Kostine M, Truchetet ME, Schaeverbeke T, Richez C. The response to TNF blockers depending on their comparator in rheumatoid arthritis clinical trials: the lessebo effect, a meta-analysis. Rheumatology (Oxford) 2021; 61:531-541. [PMID: 34382085 DOI: 10.1093/rheumatology/keab630] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 07/01/2021] [Accepted: 07/19/2021] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE To compare the effect of the biological reference agents (infliximab, etanercept, adalimumab) in rheumatoid arthritis (RA) in pivotal superiority placebo-controlled trials (reference agent vs placebo) vs their effect in equivalence active comparator-controlled trials (reference agent vs biosimilar). METHODS The PubMed, EMBASE, Cochrane, databases were searched for randomized, double-blind, controlled trials up to March 2020 comparing a biological reference agent vs placebo or biosimilar. The study assessed the American College of Rheumatology (ACR) 20/50/70 responses of the reference agent in these groups (Reference-pbo and Reference-bs, respectively). The effect of the reference agent in both groups was estimated with 95% confidence intervals (95%CI), pooled using random-effects models and then compared using a meta-regression model. RESULTS We included 31 trials. The main characteristics of the population (disease duration and activity, % seropositivity and methotrexate dose) of the population in both groups were similar. The meta-analysis found a better ACR20 response to the biological originator in the Reference-bs group with a global rate of 70% (95%CI, 66-74) compared with 59% (95%CI, 55-62) in the reference-pbo group (p= 0.001). A significant difference was also found for ACR 50 [44% (95%CI, 39-50) vs 35% (95%CI, 31-39) respectively, p< 0.01]. CONCLUSION Effect of the reference biologic agent was better when compared with an active drug to a placebo. This could be linked to an increased placebo effect in active comparator-controlled studies or a nocebo effect in placebo-controlled studies. This effect can be called the Lessebo effect.
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Affiliation(s)
- Lea Lopez
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Romain Griffier
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Thomas Barnetche
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France
| | - Edouard Lhomme
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Marie Kostine
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France.,CNRS-UMR 5164 Immuno ConcEpT, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Marie-Elise Truchetet
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France.,CNRS-UMR 5164 Immuno ConcEpT, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Thierry Schaeverbeke
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France.,CNRS-UMR 5164 Immuno ConcEpT, 146 rue Léo Saignat, 33076, Bordeaux, France
| | - Christophe Richez
- Bordeaux University Hospital, Rheumatology department, FHU ACRONIM, Place Amélie Raba Léon, 33076, Bordeaux, France.,Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France.,CNRS-UMR 5164 Immuno ConcEpT, 146 rue Léo Saignat, 33076, Bordeaux, France
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Macaluso FS, Cummings JF, Atreya R, Choi J, Orlando A. A Systematic Review on Infliximab Biosimilar SB2: From Pre-Clinical Data to Real-World Evidence. Expert Opin Biol Ther 2021; 22:203-223. [PMID: 34314284 DOI: 10.1080/14712598.2021.1958778] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION The infliximab biosimilar SB2 was approved in the EU (2016, Flixabi®) and the US (2017, Renflexis®) for the same indications as the reference product (Remicade®) based on a robust analytical and clinical data package. AREAS COVERED This systematic literature review summarizes available analytical and clinical data on SB2, including randomized controlled clinical trials and real-world evidence studies. Overall, 184 articles and congress abstracts were identified (excluding duplicates), whereof 5 reports on analytical data, four reports on two randomized controlled trials and 13 reports of real-world evidence studies were included. EXPERT OPINION The available analytical and clinical data support the equivalence of SB2 to the reference product across approved indications. This is further supported by emerging real-world evidence, particularly in extrapolated indications such as inflammatory bowel disease for both infliximab-naïve patients and patients already established on infliximab switching to SB2. Switching from originator or biosimilar infliximab to SB2 including both single and multiple switches was not associated with an increased risk of loss of treatment response or any safety or immunogenicity concerns. Overall, the approved infliximab biosimilar SB2 is safe and effective in clinical practice across licensed indications.
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Affiliation(s)
- Fabio Salvatore Macaluso
- Gastroenterologist, Inflammatory Bowel Disease Unit, "Villa Sofia-Cervello" Hospital, Strasburgo 233, 90146 Palermo, Italy
| | - Jr Fraser Cummings
- Gastroenterologist, Department of Gastroenterology, University Hospital Southampton, and University of Southampton, Tremona Road, Southampton, Hampshire SO16 6YD, UK
| | - Raja Atreya
- Gastroenterologist, Department of Medicine, Medical Clinic 1, University Hospital Erlangen, University of Erlangen-Nürnberg Erlangen, Ulmenweg 18, 91054 Erlangen, Germany
| | - Jaeyun Choi
- Manager Medical Affairs Group, Samsung Bioepis, 76, Songdogyoyuk-ro, Yeonsu-gu, Incheon, Republic of Korea
| | - Ambrogio Orlando
- Gastroenterologist, Inflammatory Bowel Disease Unit, "Villa Sofia-Cervello" Hospital, Strasburgo 233, 90146 Palermo, Italy
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Lam SW, Amoline K, Marcum C, Leonard M. Healthcare system conversion to a biosimilar: Trials and tribulations. Am J Health Syst Pharm 2021; 78:2159-2163. [PMID: 34259801 DOI: 10.1093/ajhp/zxab279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
DISCLAIMER In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE While biologic medications have transformed the care and management of millions of patients, they are a large financial strain on the healthcare system. Biosimilar medications present a great opportunity to improve care affordability. However, despite streamlined approval processes and the potential for cost savings, the acceptance and adaptation of biosimilars have been slow. This descriptive report illustrates the preparation for, challenges, and execution of an enterprise-wide biosimilar conversion within a large healthcare system. The 3 phases of biosimilar conversion utilized at our institution included selection of a biosimilar, pharmacy and therapeutics (P&T) committee approval, and implementation. SUMMARY When selecting a biosimilar, clinical data, medication safety, cost, institutional cost savings, payer coverage, patient assistance programs, and additional patient services should be taken into consideration to ensure patient care is not affected. Understanding and endorsement of biosimilar use by physician leadership, care managers, and pharmacists are crucial before implementation. P&T committee approval with clear delineation of the patient population (naive vs experienced), disease states, and whether the biosimilar would be the preferred medication should be obtained. Transparent communication of clear expectations to patients and coordination with the information technology (IT), contracting, and supply chain departments are necessary before the go-live date. Contracting and IT implementations should ideally take potential changes in biosimilar adaptation into consideration and have enough flexibility to account for these changes. Planned evaluations of patients' experiences with the change to the biosimilar should be incorporated as part of the implementation plan. CONCLUSION The barriers to biosimilar adaptation are plentiful. Careful planning, clear communication, and coordination with all affected disciplines can ensure successful biosimilar conversion.
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Affiliation(s)
- Simon W Lam
- Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA
| | - Kevin Amoline
- Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA
| | | | - Mandy Leonard
- Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA
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Massimi D, Barberio B, Bertani L, Costa F, Ferronato A, Facchin S, Cardin R, Cingolani L, Casadei C, D’Incà R, Zingone F, Savarino EV. Switching from Infliximab Originator to SB2 Biosimilar in Inflammatory Bowel Diseases: A Multicentric Prospective Real-Life Study. Therap Adv Gastroenterol 2021; 14:17562848211023384. [PMID: 34249147 PMCID: PMC8239954 DOI: 10.1177/17562848211023384] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 05/12/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Current literature still lacks studies evaluating the effectiveness and safety of switching from Infliximab originator to SB2 biosimilar in Inflammatory Bowel Diseases (IBDs). We aimed to verify the ability of SB2 to maintain the clinical and biochemical response induced by originator after switching. As secondary outcome, we aimed to verify safety, tolerability and immunogenicity of SB2 biosimilar compared with its IFX originator. METHODS We prospectively enrolled all patients who switched from originator to SB2 at three Italian IBD Units from August 2018 to April 2020. We collected clinical and biochemical data at the time of switch (T0), and at the first (T1) and the second (T2) visits after switching (mean time from switching: 135 and 329 days, respectively). In addition, data regarding therapeutic drug monitoring at T0 and T1 were recorded. RESULTS Eighty-five IBD patients (28 with Ulcerative Colitis and 57 with Crohn's Disease) were included in the study. At T1, we observed statistically significant modifications in clinical activity of disease (70 patients were in clinical remission at baseline and 60 at T1 p = 0.02), but not at T2 (p = 0.3). Fecal calprotectin values were not different both at T1 and T2 (both p = 0.9) as well as the rate of concomitant treatment with steroids (p = 0.2 and p = 0.1) or immunosuppressants (p = 0.1 and p = 1.0). Moreover, the need for therapeutic optimization from T0 to T1 and from T1 to T2 was found significant (both p = 0.01). No anti-drug antibodies were identified at T1, and no serious adverse events were recorded. CONCLUSIONS Overall, our data show that most of the patients switching from Infliximab originator to SB2 maintain the clinical and biochemical remission for at least 1 year. Further data are necessary to understand the clinical implications of these findings in the long term.
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Affiliation(s)
- Davide Massimi
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Lorenzo Bertani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Francesco Costa
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | - Sonia Facchin
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Romilda Cardin
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Linda Cingolani
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Cesare Casadei
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Renata D’Incà
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua, 35121, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Khan N, Patel D, Pernes T, Patel M, Trivedi C, Medvedeva E, Xie D, Yang YX. The Efficacy and Safety of Switching From Originator Infliximab to Single or Double Switch Biosimilar Among a Nationwide Cohort of Inflammatory Bowel Disease Patients. CROHN'S & COLITIS 360 2021; 3:otab022. [PMID: 36778941 PMCID: PMC9802034 DOI: 10.1093/crocol/otab022] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Indexed: 12/31/2022] Open
Abstract
Background Data on safety and efficacy of switching to Renflexis (SB2) from originator Infliximab (IFX) (single switch) or from originator IFX to Inflectra (CT-P13) to Renflexis (double switch) are limited. Methods We conducted a retrospective cohort study in a nationwide cohort of patient with inflammatory bowel disease (IBD) in remission who were switched to SB2. The main exposure was the treatment course of SB2. There are 2 levels in this variable: single switch (IFX to SB2) and double switch (IFX to CT-P13 to SB2). The outcome is SB2 drug discontinuation rate and/or not being in remission after 1 year. Logistic regression was used to estimate the adjusted and unadjusted odds ratios with 95% confidence intervals to study the efficacy difference between single switch and double switch. Results A total of 271 IBD patients were started on SB2. Among them 52 (19.2%) patients did not achieve remission at 1 year and 14 (5.1%) patients had to discontinue SB2 due to adverse events). In logistic regression analysis after controlling for covariates, there was no statistically significant difference observed in regard to efficacy or safety of the single switch versus double switch to SB2 (adjusted odds ratio for double switch compared to single switch = 1.33 (95% confidence interval 0.74-2.41, P = 0.3432). Conclusions Among IBD patients in remission, double switch was equally effective as compared to a single switch. This will help reassure the gastroenterologists who have concerns regarding the safety and efficacy of switching between multiple biosimilars for treating IBD.
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Affiliation(s)
- Nabeel Khan
- Corporal Michael J Crescenz VA Medical Center, Department of Gastroenterology, Philadelphia, Pennsylvania, USA,University of Pennsylvania, Perelman School of Medicine, Department of Medicine, Philadelphia, Pennsylvania, USA,Address correspondence to: Nabeel Khan, MD, Department of Gastroenterology, Corporal Michael J Crescenz VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA-19104, USA (; )
| | - Dhruvan Patel
- University of Pennsylvania, Perelman School of Medicine, Department of Gastroenterology, Philadelphia, Pennsylvania, USA
| | - Tyler Pernes
- Corporal Michael J Crescenz VA Medical Center, Department of Gastroenterology, Philadelphia, Pennsylvania, USA
| | - Manthankumar Patel
- Corporal Michael J Crescenz VA Medical Center, Department of Gastroenterology, Philadelphia, Pennsylvania, USA
| | - Chinmay Trivedi
- Corporal Michael J Crescenz VA Medical Center, Department of Gastroenterology, Philadelphia, Pennsylvania, USA
| | - Elina Medvedeva
- Corporal Michael J Crescenz VA Medical Center, Department of Gastroenterology, Philadelphia, Pennsylvania, USA
| | - Dawei Xie
- Department of Epidemiology and Biostatistics, Center of Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Yu-Xiao Yang
- Corporal Michael J Crescenz VA Medical Center, Department of Gastroenterology, Philadelphia, Pennsylvania, USA,University of Pennsylvania, Perelman School of Medicine, Department of Medicine, Philadelphia, Pennsylvania, USA,Department of Epidemiology and Biostatistics, Center of Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA,Department of Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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Smolen JS, Choe JY, Weinblatt ME, Emery P, Keystone E, Genovese MC, Myung G, Hong E, Baek I, Ghil J. Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis. RMD Open 2021; 6:rmdopen-2019-001096. [PMID: 31958281 PMCID: PMC6999676 DOI: 10.1136/rmdopen-2019-001096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 12/24/2019] [Accepted: 12/26/2019] [Indexed: 12/18/2022] Open
Abstract
Objective To evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status. Methods Patients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models. Results 1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI. Conclusion A pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity. Trial registration numbers NCT01895309, NCT01936181 and NCT02167139
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Affiliation(s)
- Josef S Smolen
- Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria
| | - Jung-Yoon Choe
- Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea
| | - Michael E Weinblatt
- Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Paul Emery
- University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK
| | - Edward Keystone
- Divison of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Mark C Genovese
- Division of Immunology and Rheumatology, Stanford University Medical Center, Stanford, California, USA
| | - Gihyun Myung
- Samsung Bioepis Co Ltd, Incheon, Republic of Korea
| | - Evelyn Hong
- Samsung Bioepis Co Ltd, Incheon, Republic of Korea
| | - Inyoung Baek
- Samsung Bioepis Co Ltd, Incheon, Republic of Korea
| | - Jeehoon Ghil
- Samsung Bioepis Co Ltd, Incheon, Republic of Korea
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Solitano V, D’Amico F, Da Rio L, Peyrin-Biroulet L, Danese S. The European Perspective and History on Biosimilars for the Treatment of Inflammatory Bowel Diseases. CROHN'S & COLITIS 360 2021; 3:otab012. [PMID: 36798960 PMCID: PMC9927805 DOI: 10.1093/crocol/otab012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
With the expiration of biologics' patents, biosimilars entered the market as a promising opportunity to reduce health-care costs in the field of inflammatory bowel diseases. Although biosimilars were initially poorly accepted, the growing evidence about their efficacy and safety has changed this situation, resulting in their widespread use. However, there is still an unmet need of improving patients' education about biosimilars to minimize nocebo responses and to accept nonmedical switching. Looking to the future, the use of recently authorized adalimumab biosimilars and the first attempts of adopting different strategies of switching (eg, cross-, multiple-) will fill some residual knowledge gaps.
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Affiliation(s)
| | | | - Leonardo Da Rio
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Address correspondence to: Silvio Danese, MD, PhD, Department of Biomedical Sciences, Humanitas University, Via R. Levi Montalcini, 20090 Pieve Emanuele, Milan, Italy ()
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Choi SJ. Biologic therapies for the treatment of rheumatoid arthritis. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2021. [DOI: 10.5124/jkma.2021.64.2.95] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial joints. If left untreated, persistent synovial inflammation can lead to cartilage and bone destruction, ultimately causing significant longterm disability and mortality. However, since the late 1990s, the combined use of methotrexate, a synthetic diseasemodifying antirheumatic drug (DMARD), and a biological DMARD has revolutionized the treatment of RA. As of 2021, the Korea Food and Drug Administration has approved seven biological DMARDs for RA treatment: four tumor necrosis factor-alpha inhibitors (infliximab, etanercept, adalimumab, and golimumab) and three non-tumor necrosis factor biological products (abatacept, rituximab, and tocilizumab). Although the use of biological products has allowed significant advances in the treatment of RA, there are certain drawbacks, such as high cost, increased infection risk, and the necessity for parenteral route product administration. Therefore, discontinuation of biological DMARD use without a resulting disease flare is the next treatment goal and a desirable result from the standpoint of risk reduction and cost-effectiveness, especially for patients with clinical remission. It is still unclear which biological product is the best. Clinicians must, therefore, personalize the sequence and strategy of treatment by considering patient characteristics, disease activity, comorbidity, and economic condition
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Ebbers HC, Fehrmann B, Ottosen M, Hvorslev N, Høier P, Hwang JW, Chung J, Lim HT, Lee S, Hong J, Rezk MF. Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars. BioDrugs 2021; 34:225-233. [PMID: 31925703 PMCID: PMC7113226 DOI: 10.1007/s40259-019-00402-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). Methods SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. Results The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. Conclusions Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies. Electronic supplementary material The online version of this article (10.1007/s40259-019-00402-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hans C Ebbers
- Biogen International GmbH, Neuhofstrasse 30, 6340, Baar, Switzerland.
| | | | - Mette Ottosen
- Biogen (Denmark) Manufacturing APS, Hillerød, Denmark
| | | | - Pia Høier
- Biogen (Denmark) Manufacturing APS, Hillerød, Denmark
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Macaluso FS, Fries W, Viola A, Centritto A, Cappello M, Giuffrida E, Privitera AC, Piccillo G, Magnano A, Vinci E, Vassallo R, Trovatello A, Belluardo N, Giangreco E, Camilleri S, Garufi S, Bertolami C, Ventimiglia M, Renna S, Orlando R, Rizzuto G, Orlando A. The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches. Inflamm Bowel Dis 2021; 27:182-189. [PMID: 32083291 DOI: 10.1093/ibd/izaa036] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. METHODS The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. RESULTS Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). CONCLUSIONS The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.
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Affiliation(s)
| | - Walter Fries
- Inflammatory Bowel Disease Unit, A.O.U. Policlinico G. Martino, Messina, Italy
| | - Anna Viola
- Inflammatory Bowel Disease Unit, A.O.U. Policlinico G. Martino, Messina, Italy
| | - Andrea Centritto
- Inflammatory Bowel Disease Unit, A.O.U. Policlinico G. Martino, Messina, Italy
| | - Maria Cappello
- Gastroenterology and Hepatology Unit, A.O.U. Policlinico G. Giaccone, Palermo, Italy
| | - Enrica Giuffrida
- Gastroenterology and Hepatology Unit, A.O.U. Policlinico G. Giaccone, Palermo, Italy
| | | | - Giovita Piccillo
- Inflammatory Bowel Disease Unit, A.O. Cannizzaro, Catania, Italy
| | - Antonio Magnano
- Gastroenterology Unit, A.O.U. Policlinico Vittorio Emanuele, Catania, Italy
| | - Elisa Vinci
- Gastroenterology Unit, A.O.U. Policlinico Vittorio Emanuele, Catania, Italy
| | - Roberto Vassallo
- Gastroenterology and Endoscopy Unit, A.O. Buccheri La Ferla Fatebenefratelli, Palermo, Italy
| | | | | | | | | | - Serena Garufi
- Gastroenterology Unit, A.O.O.R. S. Elia- M. Raimondi, Caltanissetta, Italy
| | | | - Marco Ventimiglia
- Inflammatory Bowel Disease Unit, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
| | - Sara Renna
- Inflammatory Bowel Disease Unit, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
| | - Rosalba Orlando
- Inflammatory Bowel Disease Unit, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
| | - Giulia Rizzuto
- Inflammatory Bowel Disease Unit, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
| | - Ambrogio Orlando
- Inflammatory Bowel Disease Unit, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
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Fischer S, Cohnen S, Klenske E, Schmitt H, Vitali F, Hirschmann S, Ramming A, Zundler S, Rath T, Krebs S, Dörje F, Uter W, Nagore D, Meyer S, Neurath MF, Atreya R. Long-term effectiveness, safety and immunogenicity of the biosimilar SB2 in inflammatory bowel disease patients after switching from originator infliximab. Therap Adv Gastroenterol 2021; 14:1756284820982802. [PMID: 33505519 PMCID: PMC7812413 DOI: 10.1177/1756284820982802] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 11/26/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Long-term data on inflammatory bowel disease (IBD) patients switched from originator to biosimilar infliximab SB2 are lacking. The aim of the conducted study was to investigate the effectiveness, immunogenicity and safety of a large prospectively followed-up IBD patient cohort that was entirely switched from originator infliximab to biosimilar SB2 treatment. METHODS This was a prospective, single-center, longitudinal, observational study describing clinical outcomes in IBD patients, over an 80-week period following switch from originator infliximab to SB2. Primary outcome measures were change of disease activity [Harvey-Bradshaw Index for Crohn's disease (CD), partial Mayo Score for ulcerative colitis (UC)], C-reactive protein (CRP), infliximab trough levels (TLs), anti-drug antibodies (ADAs) and adverse events. RESULTS One hundred and forty-four IBD patients (94 CD, 50 UC), with median duration of 30.5 months' (range 2-110) treatment with originator infliximab were evaluated. Mean change of disease activity compared with baseline was -0.9 (SD 2.6), -0.4 (2.2) and -0.4 (2.0) in CD; 0.1 (1.1), 0.1 (1.1) and 0.1 (1.3) in UC patients at weeks 24, 48 and 72. Median infliximab TLs were 6.2 µg/ml (interquartile range 2.3-12.2), 5.0 µg/ml (2.7-10.0), 6.6 µg/ml (3.5-12.4) and 5.1 µg/ml (2.7-10.9) at baseline and weeks 24, 48 and 72. Median CRP levels were within normal ranges throughout the study. After the switch, 9.8% of the patients developed new ADAs. Persistence on SB2 was 90% (95% confidence interval 0.85-0.95), 79% (0.72-0.86), 72% (0.64-0.80) at weeks 26, 52 and 78. Serious adverse events occurred in 11 patients. CONCLUSION Over the individual patient follow-up of 80 weeks, switch to biosimilar SB2 from originator infliximab does not result in increased disease activity or changed immunogenicity patterns. The switch to SB2 was well tolerated.
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Affiliation(s)
- Sarah Fischer
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Sarah Cohnen
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Entcho Klenske
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Heike Schmitt
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Francesco Vitali
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Simon Hirschmann
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Andreas Ramming
- Department of Medicine 3, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Sebastian Zundler
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Timo Rath
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Sabine Krebs
- Pharmacy Department, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Frank Dörje
- Pharmacy Department, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
| | - Wolfgang Uter
- Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | | | - Sebastian Meyer
- Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Markus F. Neurath
- Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen University Hospital, Erlangen, Germany
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Abstract
Over the past 2 decades, biological therapy with monoclonal antibodies targeting tumor necrosis factor-α has become a cornerstone of treatment of patients with inflammatory bowel disease. Although clinically effective, the biological therapies remain expensive, and their availability and utilization have been at times limited due to their high costs. Biosimilars are biological products similar to but not identical to the original biological agent or "reference biologic," also called "originator biologic." It is hoped that the use of biosimilars might enable these agents to become more available and, thus, decrease further expenditures related to the use of the original reference agents such as infliximab and adalimumab. In this study, we review the currently available evidence and shortcomings of these data supporting the use of biosimilars for the treatment of patients with inflammatory bowel disease, including their efficacy and safety as related to initiating therapy with biosimilar agents or switching between reference and biosimilar biologic agents.
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Caporali R, Allanore Y, Alten R, Combe B, Durez P, Iannone F, Nurmohamed MT, Lee SJ, Kwon TS, Choi JS, Park G, Yoo DH. Efficacy and safety of subcutaneous infliximab versus adalimumab, etanercept and intravenous infliximab in patients with rheumatoid arthritis: a systematic literature review and meta-analysis. Expert Rev Clin Immunol 2020; 17:85-99. [PMID: 33305638 DOI: 10.1080/1744666x.2020.1858803] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA). METHODS Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621). RESULTS The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advantage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections, and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept. CONCLUSION CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.
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Affiliation(s)
- Roberto Caporali
- Department of Clinical Sciences and Community Health, Research Centre for Adult and Pediatric Rheumatic Diseases, University of Milan, ASST Pini-CTO, Milan, Italy
| | - Yannick Allanore
- Rheumatology Department, Hôpital Cochin, Paris Descartes University, Paris, France
| | - Rieke Alten
- Department of Internal Medicine and Rheumatology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany
| | - Bernard Combe
- Department of Rheumatology, CHU, CHU Montpellier, Montpellier University, Montpellier, France
| | - Patrick Durez
- Rheumatology, Cliniques Universitaires Saint-Luc - Université Catholique De Louvain - Institut De Recherche Expérimentale Et Clinique (IREC), Brussels, Belgium
| | - Florenzo Iannone
- Rheumatology Unit, Department of Emergency and Organ Transplantation, Università Degli Studi Di Bari Aldo Moro, Bari, Italy
| | - Mike T Nurmohamed
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.,Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands
| | | | | | | | - Gahee Park
- Celltrion, Inc. Incheon, Republic of Korea
| | - Dae Hyun Yoo
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
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Kim JW, Jung JY, Suh CH. Real-world observational study of biosimilars in inflammatory arthritis treatment: a systematic literature review. Expert Opin Biol Ther 2020; 21:57-73. [PMID: 32808557 DOI: 10.1080/14712598.2020.1812575] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION The use of biological agents in patients with rheumatic diseases has achieved the therapeutic target, i.e., remission or low disease activity. The share of biological agents has been growing with the approval of biosimilars, which have been recognized for their equivalent efficacy, safety, pharmacokinetics, and immunogenicity to the original as well as their reduced economic burden. AREA COVERED Biosimilars are being examined for their bioequivalence to reference products in randomized-controlled trials; however, the use of biosimilars in actual clinical practice is complicated owing to issues with switching and comorbidities. Therefore, this review describes real-world data in the rapidly evolving field of biosimilars in the treatment of rheumatoid arthritis and spondyloarthropathy, including ankylosing spondylitis and psoriatic arthritis. EXPERT OPINION According to published data, the use of biosimilars for inflammatory arthritis led to no significant inferiority in treatment outcomes and resulted in considerable cost savings in the real-world. Currently, beyond the use of biosimilars, issues with the interchangeability of biosimilars, including immunogenicity, should be addressed. Strategies to overcome these concerns will improve treatment efficacy and safety in patients with inflammatory arthritis.
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Affiliation(s)
- Ji-Won Kim
- Department of Rheumatology, Ajou University School of Medicine , Suwon, Korea
| | - Ju-Yang Jung
- Department of Rheumatology, Ajou University School of Medicine , Suwon, Korea
| | - Chang-Hee Suh
- Department of Rheumatology, Ajou University School of Medicine , Suwon, Korea
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Immunogenicity of Biosimilars for Rheumatic Diseases, Plaque Psoriasis, and Inflammatory Bowel Disease: A Review from Clinical Trials and Regulatory Documents. BioDrugs 2020; 34:27-37. [PMID: 31721107 PMCID: PMC7042210 DOI: 10.1007/s40259-019-00394-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The goal of this narrative review was to summarize immunogenicity data of biosimilars or biosimilar candidates for rheumatic diseases, plaque psoriasis, or inflammatory bowel disease (IBD), available in peer-reviewed publications or regulatory documents. PubMed records and regulatory documents were searched for immunogenicity data of TNFα or CD20 inhibitor biosimilars or biosimilar candidates. Data collected included the proportion of patients positive for anti-drug antibodies (ADAbs), proportion with neutralizing antibodies (nAbs) among ADAb-positive patients, ADAb/nAb assay characteristics, cross-reactivity, and the effects of ADAbs on pharmacokinetics, pharmacodynamics, efficacy, and safety. We identified eight biosimilars or biosimilar candidates for adalimumab (BI 695501, SB5, ABP 501, GP2017, PF-06410293, MSB-11022, FKB-327, ZRC-3197) four for etanercept (SB4, GP2015, CHS-0214, LBEC0101), and three each for infliximab (SB2, CT-P13, GP1111) and rituximab (CT-P10, GP2013, PF-05280586) with immunogenicity data. Randomized, head-to-head trials with reference products varied in design and methodology of ADAb/nAb detection. The lowest proportions of ADAb-positive (0–13%) and nAb-positive patients (0–3%) were observed in the trials of etanercept and its biosimilars, and the highest with adalimumab, infliximab, and their biosimilars (ADAbs: ≤ 64%; nAbs: ≤ 100%). The most common method of ADAb detection was electrochemiluminescence, and ADAb positivity was associated with nominally inferior efficacy and safety. Overall, there were no significant immunogenicity differences between biosimilars and reference products. However, there are many discrepancies in assessing and reporting clinical immunogenicity. In conclusion, immunogenicity data of biosimilars or biosimilar candidates for TNFα or CD20 inhibitors were collected in trials that varied in design and procedures for ADAb/nAb detection. In general, immunogenicity parameters of biosimilars are similar to those of their reference products.
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Ditto MC, Parisi S, Priora M, Sanna S, Peroni CL, Laganà A, D'Avolio A, Fusaro E. Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis. Sci Rep 2020; 10:16178. [PMID: 32999362 PMCID: PMC7527334 DOI: 10.1038/s41598-020-73183-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 09/08/2020] [Indexed: 12/12/2022] Open
Abstract
AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.
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Affiliation(s)
- Maria Chiara Ditto
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
- Medical Science, Rheumatology Unit, Azienda Ospedaliera Universitaria di Padova, Padua, Italy.
| | - Simone Parisi
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Marta Priora
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Silvia Sanna
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Clara Lisa Peroni
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Angela Laganà
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Antonio D'Avolio
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy
| | - Enrico Fusaro
- Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
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Al Tabaa O, Etcheto A, Dumas S, Batteux F, Goulvestre C, Moltó A, Miceli-Richard C, Dougados M. Doctor's aptitude for switching from innovator etanercept to biosimilar etanercept in inflammatory rheumatic diseases: experience from a single French rheumatology tertiary care center. Eur J Clin Pharmacol 2020; 77:25-33. [PMID: 32888052 DOI: 10.1007/s00228-020-02957-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 07/09/2020] [Indexed: 12/30/2022]
Abstract
OBJECTIVES To describe the switch to biosimilar etanercept (bETN), evaluate factors associated with this switch, and evaluate the efficacy of this switch in a real-life setting METHODS: We included patients, from October 2016 to April 2017, with rheumatoid arthritis (RA) and spondyloarthritis (SpA) who received innovator ETN (iETN) for at least 6 months. After receiving information on biosimilars, all physicians were invited to propose a switch from iETN to bETN. Factors associated with bETN discontinuation were explored by univariate and multivariate analyses. We estimated the proportion of patients still on bETN over time by Kaplan-Meier survival analysis. We assessed serum trough concentrations of iETN and bETN and anti-drug antibodies to ETN. RESULTS Overall, 183 outpatients were eligible for a potential switch; 94 (51.6%) switched from iETN to bETN. The probability of a switch was greater with an older than younger aged physician (mean [SD] age 50.4 [14.3] with a switch vs 44.8 [11.3] with no switch, p = 0.005) and the physician having a full-time academic position than other position (56.4% with a switch vs 13.5% with no switch, p < 0.001). After a 6-month follow-up, bETN retention rate was 83% (95% CI: 0.76-0.92). The first cause of bETN discontinuation was inefficacy (50%). On multivariate analysis, no factor was independently associated with a bETN switch or discontinuation. Drug trough levels did not significantly differ by discontinuation or continuation of bETN. No patient showed anti-drug antibodies. CONCLUSION The probability of switching from iETN to bETN was likely related to physician characteristics.
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Affiliation(s)
- Omar Al Tabaa
- Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, EULAR center of excellence, Paris Descartes University, Paris University, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Adrien Etcheto
- Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, EULAR center of excellence, Paris Descartes University, Paris University, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Sophie Dumas
- Department of Pharmacy, Cochin Hospital, AP-HP, Paris, France
| | - Frederic Batteux
- Department of Immunology, Cochin Hospital, AP-HP, Paris, France.,Sorbonne Paris-Cité, INSERM U1016, Cochin Institute, CARPEM, Paris Descartes University, Paris University, Paris, France
| | | | - Anna Moltó
- Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, EULAR center of excellence, Paris Descartes University, Paris University, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.,INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
| | - Corinne Miceli-Richard
- Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, EULAR center of excellence, Paris Descartes University, Paris University, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. .,Immunoregulation Unit, Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Paris, France.
| | - Maxime Dougados
- Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, EULAR center of excellence, Paris Descartes University, Paris University, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.,INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France.,Immunoregulation Unit, Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Paris, France
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49
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Smolen JS, Kang YM, Yoo WH, Emery P, Weinblatt ME, Keystone EC, Genovese MC, Myung G, Baek I, Ghil J. Radiographic progression based on baseline characteristics from TNF inhibitor biosimilar studies in patients with rheumatoid arthritis. Arthritis Res Ther 2020; 22:188. [PMID: 32795341 PMCID: PMC7427775 DOI: 10.1186/s13075-020-02267-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023] Open
Abstract
Objective Phase III clinical trials of the tumour necrosis factor inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Methods Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson’s correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. Results A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson’s correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P < 0.001). Conclusions In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. Clinical trial registration numbers EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results
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Affiliation(s)
- Josef S Smolen
- Division of Rheumatology, Department of Medicine, Medical University of Vienna, Waehinger Guertel 18-20, A-1090, Vienna, Austria.
| | - Young Mo Kang
- Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Wan-Hee Yoo
- Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea
| | - Paul Emery
- University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK
| | - Michael E Weinblatt
- Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Edward C Keystone
- Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Mark C Genovese
- Division of Immunology and Rheumatology, Stanford University Medical Center, Stanford, CA, USA
| | - Gihyun Myung
- Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
| | - Inyoung Baek
- Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
| | - Jeehoon Ghil
- Samsung Bioepis Co., Ltd., Incheon, Republic of Korea
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Reynolds KA, Pithadia DJ, Lee EB, Liao W, Wu JJ. Safety and Effectiveness of Anti-Tumor Necrosis Factor-Alpha Biosimilar Agents in the Treatment of Psoriasis. Am J Clin Dermatol 2020; 21:483-491. [PMID: 32048187 DOI: 10.1007/s40257-020-00507-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Biologic drugs have revolutionized the treatment of psoriasis and other chronic inflammatory diseases. In recent years, many tumor necrosis factor-alpha 'biosimilar' agents have been developed. These biosimilars are similar in structure and function to their originator molecules, although they are not identical. Given that the safety and efficacy of the original biologic have already been proven, biosimilars are only required to show bioequivalence, or non-inferiority, to the reference biologic to be approved. Based on extrapolation of these non-inferiority data, biosimilars may be subsequently approved for all indications of the originator biologic, even without being directly studied in these various conditions. These biosimilar agents have been purported as a method to reduce the costs of biologic therapies, thereby increasing the accessibility of these medications and subsequently improving the treatment of psoriasis worldwide. The US Food and Drug Administration and/or the European Medicines Agency have approved biosimilars of adalimumab (Amjevita/Amgevita/Solymbic, Cyltezo, Imraldi/Hadlima, Hyrimoz/Hefiya/Halimatoz, Idacio, Hulio, Abrilada), etanercept (Erelzi, Benepali/Eticovo), and infliximab (Inflectra/Remsima, Renflexis/Flixabi, Ixifi/Zessly) for the treatment of psoriasis, and others are under review. There are many phase III data supporting the bioequivalence of these anti-tumor necrosis factor-alpha biosimilar agents in treating psoriasis and rheumatologic disease, which are discussed here. In general, these biosimilar agents have been shown to have equivalent efficacy, tolerability, and immunogenicity profiles compared to their originators in patients with rheumatologic disease, although studies in patients with psoriasis are fairly limited. Additional switching studies and post-marketing safety analyses are needed to assess the interchangeability of biosimilar agents with their reference products.
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Affiliation(s)
- Kelly A Reynolds
- College of Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Deeti J Pithadia
- Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Erica B Lee
- Department of Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA, USA
| | - Wilson Liao
- University of San Francisco, San Francisco, CA, USA
| | - Jashin J Wu
- Dermatology Research and Education Foundation, 4950 Barranca Pkwy, Suite 307, Irvine, CA, 92604, USA.
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