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Vallejo C, Meaney C, Clemens L, Yang K, Lukacova V, Zhou H. Physiologically Based Pharmacokinetic Models for Infliximab, Ipilimumab, and Nivolumab Developed with GastroPlus to Predict Hepatic Concentrations. Pharmaceutics 2025; 17:372. [PMID: 40143035 PMCID: PMC11945841 DOI: 10.3390/pharmaceutics17030372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Infliximab, ipilimumab, and nivolumab are three monoclonal antibodies that have been associated with hepatotoxicity. Three separate physiologically based pharmacokinetic (PBPK) models were developed in GastroPlus® to simulate plasma and liver concentrations in patient populations after administration of either infliximab, ipilimumab, or nivolumab. Methods: The models include distribution and clearance mechanisms specific to large molecules, FcRn binding dynamics, and target-mediated drug disposition (TNF-α for infliximab, CTLA-4 for ipilimumab, and PD-1 for nivolumab). Results: The PBPK model for each large molecule was able to reproduce observed plasma concentration data in patient populations, including patients with rheumatoid arthritis and patients with solid tumors. Liver concentrations were predicted to be between 10% and 23% of the plasma concentrations for each of the three drugs, aligning with previously reported results. This lends further validity to the PBPK models and their ability to accurately predict hepatic concentrations in the absence of direct tissue measurements. Conclusions: These results can be used to drive liver toxicity predictions using the quantitative systems toxicology model, BIOLOGXsym™, which integrates hepatic interstitial concentrations with in vitro mechanistic toxicity data to predict the extent of liver toxicity for biologics.
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Affiliation(s)
- Celeste Vallejo
- Simulations Plus, Research Triangle Park, Durham, NC 27709, USA; (C.M.); (L.C.); (K.Y.); (V.L.)
| | | | | | | | | | - Haiying Zhou
- Simulations Plus, Research Triangle Park, Durham, NC 27709, USA; (C.M.); (L.C.); (K.Y.); (V.L.)
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Hu X, Tang X, Li L, Luo L, He X, Yan Q, Zhong X. The efficacy of CT-P13, a biosimilar of infliximab, in inflammatory bowel diseases: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:406. [PMID: 39533176 PMCID: PMC11555959 DOI: 10.1186/s12876-024-03480-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation. METHODS Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included. RESULTS The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were naïve to biologics at 08-14 weeks were 0.66 (95% CI, 0.58-0.75) and 0.48 (95% CI, 0.43-0.54), respectively, and at 100-104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were transitioned from the original agent at 24-32 weeks were 0.84 (95% CI, 0.77-0.92) and 0.78 (95% CI, 0.63-0.93), respectively, and at 48-54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08-14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48-54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn's disease or ulcerative colitis. CONCLUSIONS CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising.
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Affiliation(s)
- Xinyue Hu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Xiaowei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Limin Li
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Lian Luo
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Xinsen He
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Qin Yan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Xiaolin Zhong
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
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Oike T, Akizue N, Ohta Y, Koseki H, Saito M, Yokoyama Y, Imai Y, Taida T, Okimoto K, Saito K, Ogasawara S, Matsumura T, Nakagawa T, Arai M, Katsuno T, Fukuda Y, Kitsukawa Y, Kato J, Kato N. Efficacy and safety of biosimilar infliximab in bio-naïve patients with Crohn's disease. Arab J Gastroenterol 2024; 25:257-262. [PMID: 38714472 DOI: 10.1016/j.ajg.2024.03.006] [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: 12/13/2022] [Revised: 02/09/2024] [Accepted: 03/23/2024] [Indexed: 05/10/2024]
Abstract
BACKGROUND AND STUDY AIMS The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease. PATIENTS AND METHODS This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration. RESULTS The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups. CONCLUSION The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease.
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Affiliation(s)
- Tsubasa Oike
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoki Akizue
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
| | - Yuki Ohta
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hirotaka Koseki
- Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, Japan
| | - Masaya Saito
- Department of Gastroenterology, Chiba Medical Center, Chiba, Japan
| | - Yuya Yokoyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yushi Imai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takashi Taida
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kenichiro Okimoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Keiko Saito
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan; Translational Research and Development Center, Chiba University Hospital, Chiba, Japan
| | - Tomoaki Matsumura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tomoo Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tatsuro Katsuno
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yoshihiro Fukuda
- Department of Gastroenterology, Chiba Medical Center, Chiba, Japan
| | - Yoshio Kitsukawa
- Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, Japan
| | - Jun Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Lichtenstein GR, Soonasra A, Latymer M, Singh S, Feagan BG. Systematic review: effectiveness and safety of switching between originator infliximab and biosimilar infliximab in patients with inflammatory bowel disease. Expert Opin Biol Ther 2024; 24:691-708. [PMID: 38979696 DOI: 10.1080/14712598.2024.2378090] [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: 04/08/2024] [Accepted: 07/05/2024] [Indexed: 07/10/2024]
Abstract
INTRODUCTION Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers. METHODS Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication. RESULTS Data from 85 publications (81 observational, two randomized controlled trials) were included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX. CONCLUSIONS Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches. PROTOCOL REGISTRATION www.crd.york.ac.uk/prospero identifier is CRD42021289144.
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Affiliation(s)
- Gary R Lichtenstein
- Department of Internal Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA
| | - Arif Soonasra
- Global Medical Affairs, Pfizer Inc., Collegeville, PA, USA
| | - Mark Latymer
- Global Medical Affairs, Pfizer Ltd., Sandwich, UK
| | - Sheena Singh
- Value and Access, Curo, Envision Pharma Group, London, UK
| | - Brian G Feagan
- Robarts Research Institute, Western University, London, ON, Canada
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Liu Y, Skup M, Yang M, Qi CZ, Wu EQ. Discontinuation and Switchback After Non-Medical Switching from Originator Tumor Necrosis Factor Alpha (TNF) Inhibitors to Biosimilars: A Meta-Analysis of Real-World Studies from 2012 to 2018. Adv Ther 2022; 39:3711-3734. [PMID: 35737227 PMCID: PMC9309144 DOI: 10.1007/s12325-022-02173-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/26/2022] [Indexed: 11/24/2022]
Abstract
INTRODUCTION To examine the prevalence rates of biosimilar discontinuation and switchback to the originator tumor necrosis factor alpha (TNF) inhibitors following non-medical switch (NMS) in patients. METHODS Real-world studies reporting biosimilar discontinuation and switchback rates following NMS published between January 2012 and August 2018 were identified through a systematic literature review. A meta-analysis estimated the annualized discontinuation and switchback rates. A subsequent meta-analysis assessed annualized incremental discontinuation rate among studies reporting both discontinuation rates in patients who underwent an NMS (switchers) and patients who remained on originators (non-switchers). RESULTS A total of 66 publications were identified: 31 in gastroenterology, 32 in rheumatology, and 3 in both. Half of the studies reported switchback rates; only 9 studies reported discontinuation rates for both switchers and non-switchers. Across studies, the mean/range sample size of the NMS patient population was 136/9-1641; mean/range follow-up was 10/3-24 months. Annualized biosimilar discontinuation rate was 21% (95% confidence interval [CI] 18%, 25%). Switchback rate was 14% (95% CI 10%, 17%) among all NMS patients and 62% (95% CI 44%, 80%) among discontinuers. The mean/range sample size of switchers and non-switchers was 344/89-1621 and 768/19-2870, respectively; mean/range follow-up was 11/6-18 and 12/6-8 months, respectively. Annualized incremental biosimilar discontinuation rate was 18% (95% CI 4%, 31%). CONCLUSION Biosimilar discontinuation was found to be prevalent among patients who underwent an NMS from an originator TNF inhibitor to its biosimilar(s) in the real world. In addition, switchback to the originator TNF inhibitors was common following biosimilar discontinuation. Careful consideration is necessary when switching patients already on an originator TNF inhibitor to its biosimilar(s). Main limitations included the heterogeneity of the studies and the limited comparability of the data.
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Affiliation(s)
- Yifei Liu
- University of Missouri-Kansas City School of Pharmacy, 1228 Health Sciences Building, 2464 Charlotte Street, Kansas City, MO, 64108, USA.
| | | | - Min Yang
- Analysis Group, Inc., Boston, MA, USA
| | | | - Eric Q Wu
- Analysis Group, Inc., Boston, MA, USA
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Tursi A, Mocci G, Allegretta L, Aragona G, Bianco MA, Colucci R, Cuomo A, Della Valle N, Ferronato A, Forti G, Gaiani F, Graziani MG, Lorenzetti R, Luzza F, Paese P, Penna A, Pica R, Pranzo G, Rodinò S, Scarcelli A, Zampaletta C, Brozzi L, Cicerone C, Cocco A, De' Angelis G, Donnarumma L, Fiorella S, Iannelli C, Larussa T, Le Grazie M, Luppino I, Meucci C, FaggianI R, Pagnini C, Perazzo P, Rodriguez-Castro KI, Sacco R, Sebkova L, Serio M, De Monti A, Picchio M, Napolitano D, Schiavoni E, Turchini L, Scaldaferri F, Pugliese D, Guidi L, Laterza L, Privitera G, Pizzoferrato M, Lopetuso LR, Armuzzi A, Elisei W, Maconi G, Papa A. Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy. Expert Opin Biol Ther 2022; 22:313-320. [PMID: 34904510 DOI: 10.1080/14712598.2022.2007881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/15/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.
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Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, Asl Bat, Andria, Italy
- Department of Medical and Surgical Sciences, Post-graduate School of Digestive Diseases Catholic University, Rome, Italy
| | - Giammarco Mocci
- Division of Gastroenterology, "Brotzu" Hospital, Cagliari, Italy
| | - Leonardo Allegretta
- Division of Gastroenterology, "Santa Caterina Novella" Hospital, Galatina, Italy
| | - Giovanni Aragona
- Division of Gastroenterology, "Guglielmo Da Saliceto" Hospital, Piacenza, Italy
| | | | - Raffaele Colucci
- Digestive Endoscopy Unit, "San Matteo Degli Infermi" Hospital, Spoleto, Italy
| | - Antonio Cuomo
- Division of Gastroenterology, "Umberto I" Hospital, Nocera Inferiore, Italy
| | - Nicola Della Valle
- Division of Gastroenterology, "Ospedali Riuniti" Hospital, Foggia, Italy
| | | | - Giacomo Forti
- Digestive Endoscopy Unit, "S. Maria Goretti" Hospital, Latina, Italy
| | - Federica Gaiani
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | | | - Roberto Lorenzetti
- Division of Gastroenterology, "Nuovo Regina Margherita" Territorial Hospital, Rome, Italy
| | - Francesco Luzza
- Department of Health Science, University of Catanzaro, Catanzaro, Italy
| | - Pietro Paese
- Division of Gastroenterology, "Annunziata" Hospital, Cosenza, Italy
| | - Antonio Penna
- Territorial Gastroenterology Service, Asl Ba, Bari, Italy
| | - Roberta Pica
- Division of Gastroenterology, Ibd Unit, "S. Pertini" Hospital, Rome, Italy
| | - Giuseppe Pranzo
- Ambulatory for Ibd Treatment, "Valle D'Itria" Hospital, Martina Franca, Italy
| | - Stefano Rodinò
- Division of Gastroenterology, "Ciaccio-pugliese" Hospital, Catanzaro, Italy
| | | | | | - Lorenzo Brozzi
- Digestive Endoscopy Unit, ULSS7 Pedemontana, Santorso, Italy
| | - Clelia Cicerone
- Division of Gastroenterology, "Annunziata" Hospital, Cosenza, Italy
| | - Andrea Cocco
- Division of Gastroenterology, Ibd Unit, "S. Pertini" Hospital, Rome, Italy
| | - Gianluigi De' Angelis
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Laura Donnarumma
- Division of Gastroenterology, "Umberto I" Hospital, Nocera Inferiore, Italy
| | | | - Chiara Iannelli
- Division of Gastroenterology, "Annunziata" Hospital, Cosenza, Italy
| | - Tiziana Larussa
- Department of Health Science, University of Catanzaro, Catanzaro, Italy
| | - Marco Le Grazie
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Ileana Luppino
- Division of Gastroenterology, "Annunziata" Hospital, Cosenza, Italy
| | - Costantino Meucci
- Division of Gastroenterology, "T. Maresca" Hospital, Torre Del Greco, Italy
| | - Roberto FaggianI
- Division of Gastroenterology, "S. Camillo" Hospital, Rome, Italy
| | - Cristiano Pagnini
- Division of Gastroenterology, "S. Giovanni - Addolorata" Hospital, Rome, Italy
| | - Patrizia Perazzo
- Division of Gastroenterology, "Guglielmo Da Saliceto" Hospital, Piacenza, Italy
| | | | - Rodolfo Sacco
- Division of Gastroenterology, "Ospedali Riuniti" Hospital, Foggia, Italy
| | - Ladislava Sebkova
- Division of Gastroenterology, "Ciaccio-pugliese" Hospital, Catanzaro, Italy
| | - Mariaelena Serio
- Division of Gastroenterology, "San Salvatore" Hospital, Pesaro, Italy
| | - Alberta De Monti
- Division of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy
| | - Marcello Picchio
- Division of General Surgery, "P. Colombo" Hospital, Velletri, Italy
| | - Daniele Napolitano
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Elisa Schiavoni
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Laura Turchini
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Franco Scaldaferri
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Daniela Pugliese
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Luisa Guidi
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Lucrezia Laterza
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Giuseppe Privitera
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Marco Pizzoferrato
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Loris R Lopetuso
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
- Department of Medicine and Ageing Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
- Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - Alessandro Armuzzi
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
| | - Walter Elisei
- Division of Gastroenterology, "S. Camillo" Hospital, Rome, Italy
| | - Giovanni Maconi
- Division of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy
| | - Alfredo Papa
- Department of Medical and Surgical Sciences, Università Cattolica Del S. Cuore and Cemad, Fondazione Policlinico Universitario "A. Gemelli," Irccs, Rome, Italy
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Hillhouse E, Mathurin K, Bibeau J, Parison D, Rahal Y, Lachaine J, Beauchemin C. The Economic Impact of Originator-to-Biosimilar Non-medical Switching in the Real-World Setting: A Systematic Literature Review. Adv Ther 2022; 39:455-487. [PMID: 34780028 PMCID: PMC8799532 DOI: 10.1007/s12325-021-01951-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/06/2021] [Indexed: 12/19/2022]
Abstract
INTRODUCTION To save costs to the healthcare system, forced non-medical switch (NMS) policies that cut drug coverage for originator biologics and fund only less expensive biosimilars are being implemented. However, costs related to the impact of NMS on healthcare resource utilization (HCRU) must also be considered. This study aims to summarize the evidence on the economic impact of an originator-to-biosimilar NMS. METHODS A systematic literature review (SLR) was conducted. Publications reporting on HCRU or costs associated with originator-to-biosimilar NMS in the real-world setting were searched in MEDLINE and EMBASE from January 2008 to February 2020. In addition to hand searching the reference lists of relevant publications and SLRs, key conference websites, PubMed, and various government sites were also searched for the 2 years preceding the search (2018-2020). RESULTS A total of 1845 citations were identified, of which 49 were retained for data extraction. Most studies reporting on the HCRU associated with NMS reported on post-NMS HCRU alone without a comparison pre-NMS. However, four studies described a difference in HCRU (i.e., investigations pre- vs post-switch or between non-switchers vs switchers), all of which reported a relative increase in HCRU, including laboratory testing, imaging, medical visits, and hospitalizations, amongst patients who underwent an originator-to-biosimilar NMS. Most studies reporting on the costs associated with NMS reported significant savings following NMS on the basis of drug costs alone. However, four studies specifically reporting on the difference of costs following originator-to-biosimilar NMS all demonstrated an increase in HCRU-related costs associated with NMS (increase in HCRU-related costs of 4-37% or 148-2234 2020 Canadian dollars). CONCLUSION Amongst the studies that reported on the difference in HCRU pre- vs post-switch or between non-switchers and switchers, all showed an increase in HCRU and related costs associated with NMS, suggesting that the expected overall savings due to less costly drug prices may be reduced as a result of an increase in HCRU and its associated costs post-switch. Nevertheless, more real-world studies that include NMS-related healthcare costs in addition to drug costs are needed.
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Affiliation(s)
- Erin Hillhouse
- PeriPharm Inc., 485 McGill St. Suite 910, Montreal, QC, H2Y 2H4, Canada
| | - Karine Mathurin
- PeriPharm Inc., 485 McGill St. Suite 910, Montreal, QC, H2Y 2H4, Canada
- University of Montreal, Montreal, QC, Canada
| | - Joëlle Bibeau
- PeriPharm Inc., 485 McGill St. Suite 910, Montreal, QC, H2Y 2H4, Canada
| | | | | | - Jean Lachaine
- PeriPharm Inc., 485 McGill St. Suite 910, Montreal, QC, H2Y 2H4, Canada
- University of Montreal, Montreal, QC, Canada
| | - Catherine Beauchemin
- PeriPharm Inc., 485 McGill St. Suite 910, Montreal, QC, H2Y 2H4, Canada.
- University of Montreal, Montreal, QC, Canada.
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Huguet JM, Cortés X, Bosca-Watts MM, Aguas M, Maroto N, Martí L, Amorós C, Paredes JM. Real-world data on the infliximab biosimilar CT-P13 (Remsima ®) in inflammatory bowel disease. World J Clin Cases 2021; 9:11285-11299. [PMID: 35071559 PMCID: PMC8717518 DOI: 10.12998/wjcc.v9.i36.11285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/04/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, biological therapies have revolutionized the management of inflammatory bowel disease (IBD); however, they are expensive. The development of biosimilar products has allowed us to reduce healthcare costs and improve patients' access to these treatments. Although various studies support the similarity between infliximab and its biosimilar CT-P13 in terms of efficacy and safety, there are unmet needs regarding research on these agents in the context of IBD. AIM To analyze clinical response rates to CT-P13 and adverse events in IBD patients treated in real-life practice. METHODS An observational, prospective, multicenter study of IBD patients treated with CT-P13 in clinical practice who were naïve to biological treatments or failed to respond to other anti-tumor necrosis factor drugs or had switched from infliximab originator was carried out. No diagnostic or follow-up interventions were conducted on patients outside usual clinical practice. The primary endpoints were clinical response rates and number of adverse events. The primary efficacy variable was the proportion of patients who were in clinical remission and/or had a clinical response at 3, 6, 9, and 12 mo. RESULTS A total of 220 IBD patients treated with CT-P13 (Remsima®) were included in the study: 87 (40%) with ulcerative colitis and 133 (60%) with Crohn's disease. Mean age of the patients was 41.47 (SD 15.74) years, and 58% were female. Nineteen (9%) patients started treatment with CT-P13 after switching from infliximab. Of the remaining 201 patients, 142 (65%) were naïve to biologic agents. At baseline, 68.6% (n = 138/201) of patients presented with active disease. After 12 mo of treatment, 14.8% (n = 12/81) presented with active disease, and 64.2% (n = 52/81) were in clinical remission without corticosteroids. After 3 mo, 75.5% (n = 115/152) had a clinical response or achieved clinical remission, which was sustained for 12 mo (85.2%; n = 69/81). There was a decrease in specific IBD indices at 3, 6, 9, and 12 mo (P < 0.001). A total of 34 adverse events were reported by 27 (12.3%) patients, 9 (26.5%) of which were serious. CONCLUSION CT-P13 is an effective and safe infliximab biosimilar for the treatment of IBD in real-life practice and may be a valid and attractive alternative for the treatment of IBD.
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Affiliation(s)
- Jose María Huguet
- Department of Gastroenterology, General University Hospital of Valencia, Valencia 46014, Spain
| | - Xavier Cortés
- Department of Gastroenterology, Hospital de Sagunto, Sagunto 46520, Spain
| | - Marta Maia Bosca-Watts
- Department of Gastroenterology, Hospital Clinico Universitario de Valencia, Valencia 46010, Spain
| | - Marian Aguas
- Department of Gastroenterology, Hospital Universitario y Politecnico la Fe de Valencia, Valencia 46026, Spain
| | - Nuria Maroto
- Department of Gastroenterology, Hospital de Manises, Manises 46940, Spain
| | - Lidia Martí
- Department of Gastroenterology, Hospital Comarcal Francesc de Borja, Gandia 46702, Spain
| | - Cirilo Amorós
- Department of Gastroenterology, Hospital Arnau de Vilanova de Valencia, Valencia 46015, Spain
| | - Jose María Paredes
- Department of Gastroenterology, Hospital Universitario Doctor Peset de Valencia, Valencia 46017, Spain
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Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn's Disease and Ulcerative Colitis-A Prospective Polish Population Study. J Clin Med 2021; 10:jcm10225311. [PMID: 34830598 PMCID: PMC8619897 DOI: 10.3390/jcm10225311] [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: 11/02/2021] [Revised: 11/09/2021] [Accepted: 11/11/2021] [Indexed: 11/29/2022] Open
Abstract
Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.
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10
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Abidin AZ, Snoswell CL, Shafiee Hanjani L, Callaghan G, Edmonds M. Infliximab switching from reference product to biosimilar: a review of evidence regarding the clinical efficacy, safety profile and immunogenicity. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2021. [DOI: 10.1002/jppr.1754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Ahmad Zainal Abidin
- Centre for Health Services Research The University of Queensland Brisbane Qld Australia
| | - Centaine L. Snoswell
- Centre for Health Services Research The University of Queensland Brisbane Qld Australia
- Pharmacy Department Princess Alexandra Hospital Brisbane Qld Australia
- School of Pharmacy The University of Queensland Brisbane Qld Australia
| | - Leila Shafiee Hanjani
- Centre for Health Services Research The University of Queensland Brisbane Qld Australia
| | - Gavin Callaghan
- Pharmacy Department Princess Alexandra Hospital Brisbane Qld Australia
| | - Michelle Edmonds
- Pharmacy Department Princess Alexandra Hospital Brisbane Qld Australia
- Pharmacy Department Royal Darwin Hospital Darwin NT Australia
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11
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Okoro RN, Hedima EW, Aguiyi-Ikeanyi CN. Knowledge, attitudes, and practices of pharmacists toward biosimilar medicines in Nigeria. J Am Pharm Assoc (2003) 2021; 62:79-85.e2. [PMID: 34654651 DOI: 10.1016/j.japh.2021.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 09/04/2021] [Accepted: 09/27/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Biopharmaceutical medicines have transformed the treatment of various long-term diseases, despite their high cost and limited availability. Due to their cost saving potentials, biosimilar medicines represent a new wave of therapy for several diseases in the next few years. Thus, pharmacists are uniquely placed to promote and enhance their uptake. OBJECTIVES The objectives of this study were to assess Nigerian pharmacists' biosimilar medicine knowledge, attitudes, and practices. METHODS This was a cross-sectional, national online survey of conveniently sampled pharmacists in Nigeria. Data were collected with a validated 31-item biosimilar medicine knowledge, attitude, and practice questionnaire. The Pearson correlation (r) analysis was conducted to investigate the association among knowledge, attitude, and practice. A P value of < 0.05 was considered statistically significant. RESULTS Of the 600 pharmacists who were invited to participate in the survey, 411 completed the questionnaire giving a response rate of 68.5%. The mean knowledge score was 6.2 ± 3.0 out of a maximum score of 14. Most of the participants (n = 268, 65.2%) had overall knowledge scores of 1 to 7. The mean attitude score was 35.0 ± 8.8 out of a maximum score of 55, whereas that of practice was 18.7 ± 5.3 out of a maximum score of 30. Knowledge was significantly positively correlated with practice (r = 0.360). CONCLUSION Most of the surveyed pharmacists had poor knowledge of biosimilar medicines, while their reported fair attitude did not translate to good practice.
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12
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Post-Marketing Pooled Safety Analysis for CT-P13 Treatment of Patients with Immune-Mediated Inflammatory Diseases in Observational Cohort Studies. BioDrugs 2021; 34:513-528. [PMID: 32356239 PMCID: PMC7223987 DOI: 10.1007/s40259-020-00421-2] [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: 02/06/2023]
Abstract
Background At EU marketing authorisation, safety data for CT-P13 (biosimilar infliximab) were limited, particularly in some indications, and uncommon adverse events (AEs) could not be evaluated among relatively small analysis populations. Objectives Our objective was to investigate the overall safety profile and incidence rate of AEs of special interest (AESIs), including serious infections and tuberculosis, in CT-P13-treated patients. Methods Data were pooled from six observational studies representing authorised indications of CT-P13 (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, adult and paediatric Crohn’s disease and ulcerative colitis). Patients were analysed by indication and treatment (patients who received CT-P13 or those who switched from reference infliximab to CT-P13 ≤ 6 months prior to enrolment or during the study). Results Overall, 4393 patients were included (n = 3677 CT-P13 group; n = 716 switched group); 64.03% of patients had inflammatory bowel disease and 6.31% of patients were antidrug antibody positive. Overall, 32.94% and 9.58% of patients experienced treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs, respectively. Across indications, TEAEs were more frequent with CT-P13 than with the switched group. Infections including tuberculosis were the most frequent serious AESI overall (2.48%) and by treatment group or indication. In total, 14 patients (0.32%) reported active tuberculosis. Overall incidence rates per 100 patient-years (95% confidence interval) were 3.40 (2.788–4.096) for serious infections including tuberculosis and 0.44 (0.238–0.732) for active tuberculosis. Infusion-related reactions were the second most frequent AESI following infection including tuberculosis. Conclusion The CT-P13 safety profile appears consistent with previous studies for CT-P13 and reference infliximab, supporting the favourable risk/benefit balance for CT-P13 treatment. Electronic supplementary material The online version of this article (10.1007/s40259-020-00421-2) contains supplementary material, which is available to authorized users.
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13
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Martínez-Lozano H, Miranda-Bautista J, González-Lama Y, Carpio D, Barreiro-de Acosta M, Pérez-Calle JL, Relea Pérez L, Villa K, Matallana V, Calvo M, Vera MI, Pérez Galindo P, Mora-Cuadrado N, López-Serrano P, Marín-Jiménez I, Menchén L. Comparison of original and biosimilar infliximab (CTP-13) in biologic-naïve patients with Crohn's disease and ulcerative colitis: a retrospective, multicenter real-life study in Spain. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS : ORGANO OFICIAL DE LA SOCIEDAD ESPANOLA DE PATOLOGIA DIGESTIVA 2021; 113:170-178. [PMID: 33213166 DOI: 10.17235/reed.2020.6847/2019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naïve, IBD patients in the real life clinical practice. METHODS a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naïve patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naïve patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. RESULTS two hundred and thirty-nine IBD biologic-naïve patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn's disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. CONCLUSIONS this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.
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Affiliation(s)
| | | | | | - Daniel Carpio
- Gastroenterología, Complexo Hospitalario Universitario de Pontevedra
| | | | | | | | - Keyla Villa
- Aparato Digestivo, Hospital Universitario Puerta de Hierro
| | | | - Marta Calvo
- Aparato Digestivo, Hospital Universitario Puerta de Hierro
| | - María I Vera
- Aparato Digestivo, Hospital Universitario Puerta de Hierro
| | | | | | | | | | - Luis Menchén
- Aparato Digestivo, Hospital General Universitario Gregorio Marañón
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14
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Talathi S, Baig KRKK. Biosimilars in inflammatory bowel disease. J Dig Dis 2020; 21:610-620. [PMID: 32920972 DOI: 10.1111/1751-2980.12940] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/11/2020] [Accepted: 09/09/2020] [Indexed: 12/11/2022]
Abstract
The advent of biologics has changed outcomes in many chronic conditions, including inflammatory bowel disease (IBD). Biologics have been used for the induction and remission of ulcerative colitis and Crohn's disease for almost two decades and are effective in patients who used to fail conventional treatment with steroids, immunomodulators. The use of biologics in the treatment of IBD has increased over the last few years, partly due to the rise in its incidence and the use of biologics as a first-line treatment in severe disease as well as in complicated diseases like penetrating/fistulating Crohn's disease. However, their use is associated with a significant burden to the society with respect to healthcare costs, resulting in the premature discontinuation of therapy in some patients, leading to exacerbations and complications. The introduction of biosimilars a decade ago seems to be a promising approach to reducing the costs related to therapy. Since their introduction, numerous studies conducted in adults and some in children show the efficacy of biosimilars with a similar side-effect profile to biologics. This review discusses the history of biosimilars in the treatment of IBD, enumerates several such studies and discusses the possibility of using biosimilars in the future.
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Affiliation(s)
- Saurabh Talathi
- Department of Pediatrics, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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15
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Bernard EJ, Fedorak RN, Jairath V. Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease. Dig Dis Sci 2020; 65:2354-2372. [PMID: 31970610 PMCID: PMC7369127 DOI: 10.1007/s10620-019-06036-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 12/28/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Biosimilar approval, such as Inflectra™ (CT-P13) for treating ulcerative colitis (UC) and Crohn's disease (CD), has reduced direct drug costs. Though clinicians are comfortable with biosimilar use in treatment-naïve patients, there are concerns in some jurisdictions that there are insufficient data from well-controlled trials to support non-medical switching. A systematic review, along with a critical assessment of the study design, was conducted to assess the potential impact of switching stable CD/UC patients from infliximab to CT-P13. METHODS A literature search using PubMed and abstracts/posters from 3 major gastroenterology conferences from 2014 to 2018 was completed. Two individual reviewers extracted data from each relevant report and compiled it into evidence tables to facilitate descriptive analyses. Key randomized trial and observational study designs were critically assessed to contextualize data relevance. RESULTS A total of 49 reports (3 randomized controlled trials, 40 observational trials, and 1 case series) were included. Most studies revealed no efficacy, safety, or immunogenicity concerns with non-medical switch. Limitations of supporting data include a small number of randomized controlled trials; predominance of observational studies with varying outcome assessments and lack of appropriate controls; and scarcity of research on biosimilar switch long-term effects. CONCLUSIONS The majority of studies suggested non-medical switch is safe. However, clinicians and regulatory bodies should be aware of differences and limitations in study designs when making inferences about the risks and benefits of switching stable IBD patients to biosimilars.
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Affiliation(s)
- Edmond-Jean Bernard
- CHUM, Université de Montréal, 1051 Rue Sanguinet, Montréal, QC H2X 3E4 Canada
| | - Richard N. Fedorak
- Faculty of Medicine and Dentistry, University of Alberta, 8440 112 St. NW, Edmonton, AB T6G 2R7 Canada
| | - Vipul Jairath
- Epidemiology and Biostatistics, Division of Gastroenterology, London Health Sciences Centre, Western University, 339 Windermere Rd, London, ON N6A 5A5 Canada
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16
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Wook Hong S, Kim YG, Ye BD. An updated review of infliximab biosimilar, CT-P13, in the treatment of immune-mediated inflammatory diseases. Immunotherapy 2020; 12:609-623. [PMID: 32517574 DOI: 10.2217/imt-2020-0086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The introduction of anti-TNFs, such as infliximab (IFX), has revolutionized the treatment of immune-mediated inflammatory diseases. Anti-TNF agents have shown outstanding efficacy and long-term improvement of clinical outcomes, but the cost has been relatively high. Out of this concern, several 'biosimilar' drugs of anti-TNF agents have been developed. CT-P13, the first biosimilar of reference IFX, was approved by the European Medicines Agency and licensed by the US FDA for use in all indications of IFX. This updated review summarizes all aspects of CT-P13, including pharmacology and pharmacokinetics, and evaluates its efficacy, safety and immunogenicity for all indications based on the results of the latest clinical trials as well as on real-world experiences.
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Affiliation(s)
- Seung Wook Hong
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong-Gil Kim
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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17
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Park SK, Moon W, Kim ES, Park SH, Park DI. Knowledge and Viewpoints on Biosimilar Monoclonal Antibodies among Asian Physicians: Comparison with European Physicians. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 74:333-340. [PMID: 31870139 DOI: 10.4166/kjg.2019.74.6.333] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 08/09/2019] [Accepted: 09/06/2019] [Indexed: 12/13/2022]
Abstract
Background/Aims Current knowledge and viewpoints regarding biosimilars among physicians in Asia are unknown, even though these were investigated by European Crohn's and Colitis Organization (ECCO) members in 2013 and 2015. Thus, this study conducted a multinational survey to assess the awareness of biosimilar monoclonal antibodies among Asian physicians. Methods A 17-question multiple-choice anonymous web survey was conducted with the logistic support of the Asian Organization of Crohn's and Colitis (AOCC). Randomly selected AOCC members were invited by e-mail to participate between February 24, 2017 and March 26, 2017. Results In total, 151 physicians from eight Asian countries responded to the survey. Most of the participants were gastroenterologists (96.6%), and 77.5% had cared for inflammatory bowel diseases (IBD) patients for more than 5 years. The majority of the respondents (66.2%) were aware that a biosimilar is similar but not equivalent to the originator. The majority of respondents (77.5%) considered cost saving to be the main advantage of biosimilars, but a high percentage of respondents (38.4%) were concerned about a different immunogenicity from that of the originator (92.4% and 27.1% respectively in ECCO 2015). Only 19.2% considered that the originator and biosimilars were interchangeable, and only 6.0% felt very confident in the use of biosimilars (44.4% and 28.8% respectively in ECCO 2015). Conclusions Asian gastroenterologists in 2017 are generally well informed about biosimilars. On the other hand, compared to the ECCO members surveyed in 2015, Asian gastroenterologists had more concerns and less confidence about the use of biosimilars in clinical practice. Thus, IBD-specific data on the comparison of the efficacy, safety, and immunogenicity in Asian patients are needed.
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Affiliation(s)
- Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Sang Hyun Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Astier A. [Interchangeability and substitution of biosimilars]. ANNALES PHARMACEUTIQUES FRANÇAISES 2020; 78:277-284. [PMID: 32387176 DOI: 10.1016/j.pharma.2020.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 04/17/2020] [Accepted: 04/27/2020] [Indexed: 12/26/2022]
Abstract
The rationality of the interchangeability of biosimilars is based on broad scientific evidence and numerous clinical experiences in real life which show no sign of reduced efficacy or different tolerance compared to the original molecule. The substitution of biosimilars (pharmaceutical act) remains widely contested in many countries, notably in France. However, it would make it possible to make very significant savings in a context of major acceleration in health spending. This reluctance is unfounded in light of the quality of biosimilars authorized in Europe and their rigorous evaluation. It is therefore essential to improve the information of health professionals and patients on these biosimilars.
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Affiliation(s)
- A Astier
- Biotopic pharmaceuticals, 16, rue Gay-Lussac, 75005 Paris, France.
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19
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Park SH, Park JC, Lukas M, Kolar M, Loftus EV. Biosimilars: concept, current status, and future perspectives in inflammatory bowel diseases. Intest Res 2020; 18:34-44. [PMID: 32013313 PMCID: PMC7000642 DOI: 10.5217/ir.2019.09147] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/28/2019] [Accepted: 12/28/2019] [Indexed: 12/13/2022] Open
Abstract
The inflammatory bowel diseases (IBD), which consist of Crohn's disease and ulcerative colitis, are chronic, incurable immunemediated inflammatory disorders of the intestine. As IBD incidence continues to increase globally and its mortality is low, prevalent cases of IBD are rapidly increasing, thereby leading to a substantial increase in health care costs. Although the introduction of biologic agents for IBD management has revolutionized the armamentarium of IBD therapy, the high cost of this therapy is concerning. With the expirations of patents for existing biologic agents (originals), biosimilars with cheaper costs have been highlighted in the field of IBD. Despite concerns regarding their short- and long-term efficacy, safety, immunogenicity, and interchangeability, increasing evidence via prospective observations and phase III or IV clinical trials, which aim to prove the "biosimilarity" of biosimilars to originals, has partly confirmed their efficacy, safety, and interchangeability. Additionally, although patients and physicians are reluctant to use biosimilars, a positive budget impact has been reported owing to their use in different countries. In the near future, multiple biosimilars with lower costs, and efficacy and safety profile similar to originals, could be used to treat IBD; thus, further consideration and knowledge dissemination are warranted in this new era of biosimilars.
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Affiliation(s)
- Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Cheol Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Milan Lukas
- IBD Clinical and Research Centre, ISCARE Lighthouse and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Martin Kolar
- IBD Clinical and Research Centre, ISCARE Lighthouse and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Edward V. Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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An updated systematic review and meta-analysis about the safety and efficacy of infliximab biosimilar, CT-P13, for patients with inflammatory bowel disease. Int J Colorectal Dis 2019; 34:1633-1652. [PMID: 31492986 DOI: 10.1007/s00384-019-03354-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/15/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE We aimed to evaluate the efficacy and safety of infliximab biosimilar, CT-P13, for patients with inflammatory bowel disease. METHODS We searched PubMed, Scopus, Ovid, and Web of Science for relevant clinical trials discussing CT-P31 administration for IBD patients either naïve to biological therapy or switched from IFX therapy. Data of the rates of clinical response, clinical remission, and adverse events were extracted and pooled in a random effect model meta-analysis using CMA version 2. RESULTS Thirty-two studies with a total of 3464 IBD patients treated with CT-P13 were identified. The pooled rates of clinical response among Crohn's disease (CD) and ulcerative colitis (UC) at 8-14 weeks were 0.81 (95% CI = 0.72 to 0.87) and 0.68 (95% CI = 0.63 to 0.72), respectively, and at 48-63 weeks were 0.69 (95% CI = 0.48 to 0.85) and 0.54 (95% CI = 0.45 to 0.63) respectively. After switching from IFX to CT-P13, the pooled rates of sustained clinical response among CD and UC at 30-32 weeks were 0.84 (95% CI = 0.57 to 0.96) and 0.96 (95% CI = 0.58 to 0.99), respectively, and at 48-63 weeks were 0.51 (95% CI = 0.22 to 0.79) and 0.83 (95% CI = 0.19 to 0.99) respectively. Moreover, adverse events were reported (CD = 0.10, 95% CI 0.04 to 0.22; UC = 0.18, 95% CI 0.05 to 0.15). CONCLUSION CT-P13 is effective and well tolerated in short and long-term periods. Switching to CT-P13 is recommended for the management of IBD.
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Kim NH, Lee JH, Hong SN, Yoon H, Kang HW, Lee SH, Im JP, Cha JM, Eun CS, Kim JW, Choi CH, Park DI. Long-term efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study. J Gastroenterol Hepatol 2019; 34:1523-1532. [PMID: 30828891 DOI: 10.1111/jgh.14645] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 02/05/2019] [Accepted: 02/26/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM A biosimilar of infliximab, CT-P13 (Remsima®) has the potential to reduce treatment costs and enhance access to biological therapy for inflammatory bowel disease (IBD) patients. However, long-term clinical data on its use for IBD treatment are currently sparse. We aimed to investigate the long-term efficacy and safety of CT-P13 therapy in a large, real-life IBD cohort. METHODS A total of 368 IBD patients (227 with Crohn's disease [CD] and 141 with ulcerative colitis [UC]) treated with CT-P13 at 16 referral hospitals in Korea between July 2012 and December 2017 were retrospectively analyzed. RESULTS The cumulative retention rates at years 1, 3, and 5 were 86.1%, 68.5%, and 58.7% and 69.7%, 46.0%, and 26.7% in anti-tumor necrosis factor (TNF)-naïve CD and UC patients, respectively. The clinical response and remission rates at week 14 and at years 1, 3, and 5 were 94.3%, 92.7%, 76.8%, and 17.6% and 78.6%, 82.4%, 72.2%, and 17.6% in anti-TNF-naïve CD and 85.6%, 80.0%, 55.2%, and 6.7% and 42.6%, 59.8%, 44.2%, and 6.7% in anti-TNF-naïve UC patients, respectively. Among patients who switched from the biologic originator to CT-P13, the cumulative retention rates at years 1, 3, and 5 were 88.5%, 66.1%, and 44.8% in CD, and 73.9%, 42.5%, and 42.5% in UC patients, respectively. Significant improvements in disease activity scores were accompanied by marked reductions in inflammatory marker levels, and no unexpected adverse events including death or malignancy occurred during the study period. CONCLUSIONS Long-term treatment with CT-P13 is effective in inducing and maintaining disease improvement and is well-tolerated in patients with IBD. CT-P13 may be a promising treatment option for IBD.
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Affiliation(s)
- Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hyun Lee
- Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital, Seoul, Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyoun Woo Kang
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Suck-Ho Lee
- Digestive Endoscopic Center, Esoo Hospital, Cheonan-si, Korea
| | - Jong Pil Im
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Ji Won Kim
- Department of Internal Medicine, SMG-SNU Boramae Medical Center, SNUH College of Medicine, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Albshesh A, Ben-Horin S. CT-P13: a review on a biosimilar to infliximab in the treatment of inflammatory bowel disease. Expert Opin Biol Ther 2019; 19:971-978. [PMID: 31401899 DOI: 10.1080/14712598.2019.1653848] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: CT-P13 was developed as an infliximab biosimilar in 2013. The primary structure of CT-P13 is identical to that of original infliximab and it has highly similar higher order structure, physiochemical characteristics, and biological properties. To date, data from real-life cohorts and randomized controlled trials show comparable clinical efficacy, safety and immunogenicity of biosimilar CT-P13, and the original reference medicinal Product (RMP). Areas covered: This article reviews the comparability of CT-P13 and the RMP and focuses on the emerging clinical trial and observational cohorts data on efficacy and safety of CT-P13 in inflammatory bowel disease (IBD) patients. The development of a subcutaneous formulation of Infliximab CT-P13 is also addressed. Expert opinion: There is a plethora of evidence to show CT-P13 is non-inferior to infliximab RMP in IBD and that a switch from RMP to this biosimilar is feasible and safe. However, interchangeability and multiple switches can still not be endorsed for introduction into clinical practice.
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Affiliation(s)
- Ahmad Albshesh
- Department of Gastroenterology, Sheba medical center, Sackler School of Medicine Tel-Aviv University , Israel
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba medical center, Sackler School of Medicine Tel-Aviv University , Israel
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Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, Makharia GK, Pisespongsa P, Chen MH, Ran ZH, Ye BD, Park DI, Ling KL, Ong D, Ahuja V, Goh KL, Sollano J, Lim WC, Leung WK, Ali RAR, Wu DC, Ong E, Mustaffa N, Limsrivilai J, Hisamatsu T, Yang SK, Ouyang Q, Geary R, De Silva JH, Rerknimitr R, Simadibrata M, Abdullah M, Leong RWL. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. J Gastroenterol Hepatol 2019; 34:1296-1315. [PMID: 30848854 DOI: 10.1111/jgh.14648] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/05/2019] [Accepted: 03/02/2019] [Indexed: 02/05/2023]
Abstract
The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
- Duke-NUS Medical School, Singapore
| | - Ida Hilmi
- Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, New Delhi, India
| | | | - Siew Chien Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | - Min Hu Chen
- Division of Gastroenterology, The First University Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhi Hua Ran
- Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Byong Duk Ye
- Department of Gastroenterology and IBD Center, University of Ulsan College of Medicine, Ulsan, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | - David Ong
- Division of Gastroenterology & Hepatology, University Medicine Cluster, National University Hospital of Singapore, Singapore
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Khean Lee Goh
- University of Malaya Specialist Centre, Kuala Lumpur, Malaysia
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Wee Chian Lim
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore
| | - Wai Keung Leung
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Hong Kong, Hong Kong
| | | | - Deng Chyang Wu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Evan Ong
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Nazri Mustaffa
- Department of Internal Medicine, School of Medical Sciences, Health Campus, Universiti Sains, George Town, Malaysia
| | - Julajak Limsrivilai
- Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan
| | - Suk Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Ulsan, Korea
| | - Qin Ouyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Richard Geary
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | | | | | - Marcellus Simadibrata
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Department of Internal Medicine, Dr Cipto Mangankusumo National Hospital, Central Jakarta, Indonesia
| | - Rupert W L Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
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Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, Makharia GK, Pisespongsa P, Chen MH, Ran ZH, Ye BD, Park DI, Ling KL, Ong D, Ahuja V, Goh KL, Sollano J, Lim WC, Leung WK, Ali RAR, Wu DC, Ong E, Mustaffa N, Limsrivilai J, Hisamatsu T, Yang SK, Ouyang Q, Geary R, De Silva JH, Rerknimitr R, Simadibrata M, Abdullah M, Leong RWL. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. Intest Res 2019; 17:285-310. [PMID: 31146509 PMCID: PMC6667368 DOI: 10.5217/ir.2019.00026] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/10/2019] [Accepted: 04/15/2019] [Indexed: 02/07/2023] Open
Abstract
The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
- Duke-NUS Medical School, Singapore
| | - Ida Hilmi
- Department of Medicine, Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, New Delhi, India
| | | | - Siew Chien Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pises Pisespongsa
- Gastroenterology and Hepatology, Bumrungrad International University, Bangkok, Thailand
| | - Min Hu Chen
- Division of Gastroenterology, The First University Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhi Hua Ran
- Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Byong Duk Ye
- Department of Gastroenterology and IBD Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | - David Ong
- Division of Gastroenterology and Hepatology, National University Hospital of Singapore, University Medicine Cluster, Singapore
| | - Vineet Ahuja
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Khean Lee Goh
- University of Malaya Specialist Centre, Kuala Lumpur, Malaysia
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Wee Chian Lim
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore
| | - Wai Keung Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Hong Kong
| | - Raja Affendi Raja Ali
- Faculty of Medicine, UKM Medical and Specialist Centres, The National University of Malaysia, Kuala Lumpur, Malaysia
| | - Deng Chyang Wu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Evan Ong
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Nazri Mustaffa
- Department of Internal Medicine, School of Medical Sciences, Health Campus, Sains University, Kubang Kerian, Malaysia
| | - Julajak Limsrivilai
- Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan
| | - Suk Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
| | - Qin Ouyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Richard Geary
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | | | | | - Marcellus Simadibrata
- Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Department of Internal Medicine, Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Rupert WL Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, Australia
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25
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Guerra Veloz MF, Belvis Jiménez M, Valdes Delgado T, Castro Laria L, Maldonado Pérez B, Perea Amarillo R, Merino Bohórquez V, Caunedo Álvarez Á, Vilches Arenas Á, Argüelles-Arias F. Long-term follow up after switching from original infliximab to an infliximab biosimilar: real-world data. Therap Adv Gastroenterol 2019; 12:1756284819858052. [PMID: 31258621 PMCID: PMC6585238 DOI: 10.1177/1756284819858052] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/23/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Several studies have reported positive efficacy outcomes for patients with inflammatory bowel disease treated with CT-P13, an infliximab biosimilar. Data from follow-up periods longer than 1 year are still scarce. Here, we assessed the long-term efficacy data, loss of response and safety after switching from infliximab to CT-P13 in patients with inflammatory bowel disease. METHODS This was a prospective single-center observational study involving patients with moderate-to-severe Crohn's disease and ulcerative colitis switched from infliximab to CT-P13 treatment and reviewed up to 24 months. Efficacy and loss of response were measured using the Harvey-Bradshaw (HB) index and partial Mayo score for patients with Crohn's disease and ulcerative colitis respectively. C-reactive protein, infliximab drug levels, adverse events and antidrug antibodies were also monitored throughout the study. RESULTS A total of 64 patients with Crohn's disease and 36 patients with ulcerative colitis were included. Most of them (72%) remained on CT-P13. Overall, 28% of patients discontinued the therapy due to loss of response, adverse events or long-lasting clinical remission. Remission at 18 and 24 months occurred in 69.9% and 68.5% of patients, respectively. Dose increase was performed in 22% of patients, with remission being reached in 60% of them. HB index, partial Mayo score, C-reactive protein and infliximab drug levels did not show significant changes. Serious adverse events were reported in 14% of patients. Overall, two patients developed low levels of antidrug antibodies. CONCLUSIONS Most of the patients switching from original infliximab were maintained on CT-P13 at 2 years of follow up with a good profile of efficacy and safety.
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Affiliation(s)
| | - María Belvis Jiménez
- Gastroenterology Department, Virgen Macarena University Hospital, Seville, Spain
| | | | - Luisa Castro Laria
- Gastroenterology Department, Virgen Macarena University Hospital, Seville, Spain
| | | | - Raúl Perea Amarillo
- Gastroenterology Department, Virgen Macarena University Hospital, Seville, Spain
| | | | | | - Ángel Vilches Arenas
- Preventive Medicine and Public Health, University Hospital Virgen Macarena, Seville, Spain
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Fiorino G, Caprioli F, Daperno M, Mocciaro F, Principi M, Viscido A, Fantini MC, Orlando A, Papi C, Annese V, Danese S, Vecchi M, Rizzello F, Armuzzi A. Use of biosimilars in inflammatory bowel disease: a position update of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis 2019; 51:632-639. [PMID: 30872085 DOI: 10.1016/j.dld.2019.02.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/03/2019] [Accepted: 02/04/2019] [Indexed: 12/11/2022]
Abstract
The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.
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Affiliation(s)
- Gionata Fiorino
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy, and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan, Italy
| | - Marco Daperno
- Division of Gastroenterology, Ospedale Ordine Mauriziano di Torino, Turin, Italy
| | - Filippo Mocciaro
- Gastroenterology and Endoscopy Unit, A.R.N.A.S Civico-Di Cristina-Benfratelli Hospital, Palermo, Italy
| | - Mariabeatrice Principi
- Gastroenterology Unit, Department of Organ Transplantation (DETO), Policlinico Universitario, Bari, Italy
| | - Angelo Viscido
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | | | - Ambrogio Orlando
- IBD Unit, A.O. Osp. Riuniti "Villa Sofia-Cervello", Palermo, Italy
| | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | | | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Maurizio Vecchi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy, and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan, Italy
| | | | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.
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Tursi A, Mocci G, Faggiani R, Allegretta L, Valle ND, Forti G, Franceschi M, Ferronato A, Gallina S, Larussa T, Luzza F, Lorenzetti R, Penna A, Rodino S, Sebkova L, Lauria A, Piergallini S, Pranzo G, Ricciardelli C, Zampaletta C, Elisei W, Picchio M. Infliximab biosimilar CT-P13 is effective and safe in treating inflammatory bowel diseases: a real-life multicenter, observational study in Italian primary inflammatory bowel disease centers. Ann Gastroenterol 2019; 32:392-399. [PMID: 31263362 PMCID: PMC6595921 DOI: 10.20524/aog.2019.0377] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 04/01/2019] [Indexed: 12/24/2022] Open
Abstract
Background The purpose of this study was to assess the efficacy and safety of biosimilar infliximab (IFX) CT-P13 in treating outpatients with inflammatory bowel disease (IBD) in Italian primary gastroenterology centers. Methods Consecutive IBD outpatients who completed the induction treatment were evaluated retrospectively. Clinical activity was scored according to the Mayo score for ulcerative colitis (UC) and to the Harvey-Bradshaw Index (HBI) for Crohn’s disease (CD). The primary endpoint was the achievement of clinical remission (Mayo score ≤2 in UC and HBI ≤5 in CD). Secondary endpoints were clinical response to treatment, achievement of mucosal healing, and safety. Results One hundred forty-one patients (96 UC and 45 CD) were enrolled. Previous treatment with anti-tumor necrosis factor (TNF)α had been provided to 26% of UC patients and 28.9% of CD patients. Remission was achieved in 57.3% UC patients and in 75.6% CD patients during a median (interquartile range) follow up of 24 (6-24) months. Clinical response and mucosal healing were achieved in 87.5% and 75.0% of UC patients and in 84.4% and 84.2% of CD patients, respectively. By both univariate and multivariate analysis, age >40 years, presence of comorbidities, and naivety to anti-TNFα were significantly related to remission. Only one (0.7%) adverse event was reported in the CD group. Surgery was performed in 2.1% of UC patients and 6.7% of CD patients. Switching from IFX originator to biosimilar did not influence the maintenance of the clinical remission. Conclusion This study confirmed the long-term efficacy and safety of CT-P13 therapy in IBD, in both naïve patients and those switching from IFX originator.
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Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, Andria (Antonio Tursi)
| | - Giammarco Mocci
- Division of Gastroenterology, "Brotzu" Hospital, Cagliari (Giammarco Mocci)
| | - Roberto Faggiani
- Division of Gastroenterology, "Belcolle" Hospital, Viterbo (Roberto Faggiani, Sara Gallina, Costantino Zampaletta)
| | - Leonardo Allegretta
- Division of Gastroenterology, "Santa Caterina Novella" Hospital, Galatina, LE (Leonardo Allegretta)
| | - Nicola Della Valle
- Division of Gastroenterology, A.O. "Ospedali Riuniti", Foggia (Nicola Della Valle)
| | - Giacomo Forti
- Division of Digestive Endoscopy, "S. Maria Goretti" Hospital, Latina (Nicola Della Valle, Giacomo Forti)
| | - Marilisa Franceschi
- Digestive Endoscopy Unit, ULSS7 Pedemontana, Santorso (VI) (Marilisa Franceschi, Antonio Ferronato)
| | - Antonio Ferronato
- Digestive Endoscopy Unit, ULSS7 Pedemontana, Santorso (VI) (Marilisa Franceschi, Antonio Ferronato)
| | - Sara Gallina
- Division of Gastroenterology, "Belcolle" Hospital, Viterbo (Roberto Faggiani, Sara Gallina, Costantino Zampaletta)
| | - Tiziana Larussa
- Department of Health Science, University of Catanzaro, Catanzaro (Tiziana Larussa, Francesco Luzza)
| | - Francesco Luzza
- Department of Health Science, University of Catanzaro, Catanzaro (Tiziana Larussa, Francesco Luzza)
| | - Roberto Lorenzetti
- Division of Gastroenterology, PTP "Nuovo Regina Margherita", Rome (Roberto Lorenzetti)
| | - Antonio Penna
- Division of Gastroenterology, "S. Paolo" Hospital, Bari (Antonio Penna)
| | - Stefano Rodino
- Division of Gastroenterology, "Ciaccio-Pugliese" Hospital, Catanzaro (Stefano Rodino, Ladislava Sebkova)
| | - Ladislava Sebkova
- Division of Gastroenterology, "Ciaccio-Pugliese" Hospital, Catanzaro (Stefano Rodino, Ladislava Sebkova)
| | - Angelo Lauria
- Division of Gastroenterology, A.O. "Bianchi-Melacrino-Morelli", Reggio Calabria (Angelo Lauria)
| | - Simona Piergallini
- Division of Gastroenterology, IBD Unit, "A. Murri" Hospital, Fermo (Simona Piergallini)
| | - Giuseppe Pranzo
- Ambulatory for IBD Treatment, "Valle D'Itria" Hospital, Martina Franca (TA) (Giuseppe Pranzo)
| | - Cristina Ricciardelli
- Division of Gastroenterology, "Veris Delli Ponti" Hospital, Scorrano (LE) (Cristina Ricciardelli)
| | - Costantino Zampaletta
- Division of Gastroenterology, "Belcolle" Hospital, Viterbo (Roberto Faggiani, Sara Gallina, Costantino Zampaletta)
| | - Walter Elisei
- Division of Gastroenterology, ASL Roma 6, Albano Laziale, Rome (Walter Elisei)
| | - Marcello Picchio
- Division of General Surgery, "P. Colombo" Hospital, ASL Roma 6, Velletri, Rome (Marcello Picchio), Italy
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Milassin Á, Fábián A, Molnár T. Switching from infliximab to biosimilar in inflammatory bowel disease: overview of the literature and perspective. Therap Adv Gastroenterol 2019; 12:1756284819842748. [PMID: 31019554 PMCID: PMC6469269 DOI: 10.1177/1756284819842748] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 03/15/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Biological therapy has revolutionized the treatment of inflammatory bowel disease (IBD). After the expiration of patents for biological innovator products, development of biosimilars increased. CT-P13 was the first biosimilar approved for the same indications as the reference product; however, the approval was based on extrapolated data from rheumatoid arthritis and ankylosing spondylitis. Our aim was to review clinical studies about switching from originator infliximab (IFX-O) to biosimilar infliximab (IXF-B) in IBD, focusing on recently published data and the future of biosimilars. METHODS The PubMed database was searched for original articles published up to 1 December 2018 reporting data on IFX-B in IBD. RESULTS A total of 29 studies assessing switching from IFX-O to IFX-B, 14 assessing induction therapy with IFX-B were found. Efficacy, safety and immunogenicity were discussed. Studies confirm that CT-P13 is safe and equally efficient as the reference product for both induction and maintenance therapy; and that switching from the reference product to biosimilar is non-inferior to continuous biosimilar use. However, efficacy and safety data on Flixabi (SB2) in IBD patients is lacking. CONCLUSION Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching and cross-switching among biosimilars in IBD patients.
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Affiliation(s)
- Ágnes Milassin
- First Department of Medicine, University of
Szeged, Hungary
| | - Anna Fábián
- First Department of Medicine, University of
Szeged, Hungary
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29
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Danese S, Fiorino G. Anti-TNF Biosimilars in Inflammatory Bowel Disease: Searching the Proper Patient's Profile. Curr Med Chem 2019; 26:280-287. [PMID: 29756565 DOI: 10.2174/0929867325666180514100204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 10/08/2017] [Accepted: 04/20/2018] [Indexed: 12/24/2022]
Abstract
Biosimilars of infliximab (CT-P13) are currently approved and available for the same indications as for the originator. Some concerns about safety and immunogenicity have risen in the past because of lack of data in IBD. Since 2015, several cohort studies have been conducted in IBD showing that CT-P13 has comparable safety and efficacy profile to the originator, both in adult and pediatric population, either in naïve patients or even in those who switched from the originator to CT-P13. This review aims to analyze the current literature data in order to define a clear patient profile, to identify those IBD patients who would benefit the most from the use of CT-P13.
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Affiliation(s)
- Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy.,Departmentof Biomedical Science, Humanitas University, Rozzano, Milan, Italy
| | - Gionata Fiorino
- IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy
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30
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Martelli L, Peyrin-Biroulet L. Efficacy, Safety and Immunogenicity of Biosimilars in Inflammatory Bowel Diseases: A Systematic Review. Curr Med Chem 2019; 26:270-279. [DOI: 10.2174/0929867323666161014153346] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 10/03/2016] [Accepted: 10/03/2016] [Indexed: 12/24/2022]
Abstract
Background: Anti-tumor necrosis factor (anti-TNF) monoclonal antibodies have
revolutionized the treatment of inflammatory bowel diseases (IBD). However, because of
their complexity, their production is expensive contributing to their high price. As the patent
protection of these therapies has expired in several countries, biosimilars have been developed
to reduce the healthcare costs. The aim of this article is to review the literature on the
safety, efficacy and immunogenicity of biosimilars in IBD.
</P><P>
Methods: A PubMed literature search was performed using the following terms until May
2016: ‘biosimilars’, ‘CT-P13’, ‘infliximab’, ‘Crohn’s disease’, ‘ulcerative colitis’, ‘inflammatory
bowel diseases’, ‘efficacy’, ‘safety’, ‘immunogenicity’. Additionally, abstracts from international
meetings were also reviewed.
</P><P>
Results: A total of eleven studies in IBD patients provided real-world evidence on the efficacy,
safety and immunogenicity profile of biosimilars in IBD patients. Based on the available
evidence, CT-P13 is efficacious and well tolerated in IBD patients in a real-life setting.
The vast majority of studies only included IBD patients who had never received biological
therapies. Information regarding the interchangeability between CT-P13 and its originator is
currently being investigated in the NOR-SWITCH trial. Otherwise, the immunogenicity profile
of CT-P13 seems to be similar to the originator.
</P><P>
Conclusion: The infliximab biosimilar seems to be efficacious, safe and with a similar immunogenicity
profile as the originator in IBD. Large prospective post-marketing studies are
needed to assess the long-term safety profile of CT-P13. The use of infliximab biosimilars
may lead to major healthcare cost savings.
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Affiliation(s)
- Laura Martelli
- Department of Hepato-Gastroenterology, University Hospital of Nancy, Universite de Lorraine, Vandoeuvre- les-Nancy, France
| | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Universite de Lorraine, Vandoeuvre-les-Nancy, France
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31
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Esteban E, Bustos RH, García JC, Jáuregui E. Biosimilars: An Approach to some Current Worldwide Regulation Frameworks. ACTA ACUST UNITED AC 2019; 14:16-40. [DOI: 10.2174/1574884713666181025142928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 10/12/2018] [Accepted: 10/19/2018] [Indexed: 12/26/2022]
Abstract
Developing new biologics has led to regulations and norms aimed at guaranteeing their
safety, quality and effectiveness, in terms of marketing, prescription, use, interchangeability and
switching. Biologics are of great importance in treating patients suffering from rheumatic, autoimmune,
inflammatory and neoplastic diseases. The expiry/lapse of reference biologics or originators’
patents has meant that developing biosimilars involves accompanying legal requirements for their
approval in countries worldwide. This paper has thus approached the situation of biosimilar regulation
worldwide, the pertinent technical concepts and regulatory differences in some countries of
interest.
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Affiliation(s)
- Efraín Esteban
- Evidence-Based Therapeutic Group, Clinical Pharmacology, Universidad de la Sabana, Chia, Colombia
| | - Rosa-Helena Bustos
- Evidence-Based Therapeutic Group, Clinical Pharmacology, Universidad de la Sabana, Chia, Colombia
| | - Julio-César García
- Evidence-Based Therapeutic Group, Clinical Pharmacology, Universidad de la Sabana, Chia, Colombia
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Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater EF, Stoff B, Armstrong AW, Connor C, Cordoro KM, Davis DMR, Elewski BE, Gelfand JM, Gordon KB, Gottlieb AB, Kavanaugh A, Kiselica M, Korman NJ, Kroshinsky D, Lebwohl M, Leonardi CL, Lichten J, Lim HW, Mehta NN, Paller AS, Parra SL, Pathy AL, Rupani RN, Siegel M, Wong EB, Wu JJ, Hariharan V, Elmets CA. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol 2019; 80:1029-1072. [PMID: 30772098 DOI: 10.1016/j.jaad.2018.11.057] [Citation(s) in RCA: 564] [Impact Index Per Article: 94.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 11/26/2018] [Accepted: 11/27/2018] [Indexed: 12/29/2022]
Abstract
Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.
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Affiliation(s)
| | - Bruce E Strober
- University of Connecticut, Farmington, Connecticut; Probity Medical Research, Waterloo, Ontario, Canada
| | | | | | | | | | | | | | - Kelly M Cordoro
- University of California, San Francisco School of Medicine, Department of Dermatology, San Francisco, California
| | | | | | - Joel M Gelfand
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | | | - Alice B Gottlieb
- Department of Dermatology, Icahn School of Medicine at Mt. Sinai, New York
| | | | | | - Neil J Korman
- University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | | | - Mark Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mt. Sinai, New York
| | | | | | - Henry W Lim
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
| | - Nehal N Mehta
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
| | - Amy S Paller
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Arun L Pathy
- Colorado Permanente Medical Group, Centennial, Colorado
| | | | | | - Emily B Wong
- San Antonio Uniformed Services Health Education Consortium, Joint-Base San Antonio
| | - Jashin J Wu
- Dermatology Research and Education Foundation, Irvine, California
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Guerra Veloz MF, Vázquez Morón JM, Belvis Jiménez M, Pallarés Manrique H, Valdés Delgado T, Castro Laria L, Maldonado Pérez B, Benítez Roldán A, Perea Amarillo R, Merino V, Caunedo Álvarez Á, Argüelles Arias F. Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: results of a multicenter study after 12 months. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 110:564-570. [PMID: 29893581 DOI: 10.17235/reed.2018.5368/2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switching from the reference product (RP), infliximab, to CT-P13 in patients with IBD. METHODS this was a multicenter prospective observational study in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade®) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were monitored and recorded throughout the study. RESULTS a total of 167 patients (116 CD/51 UC) were included; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remission at 12 months. The Harvey-Bradshaw (HB) score significantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. CONCLUSION switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.
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Affiliation(s)
| | | | | | | | | | | | - Belén Maldonado Pérez
- Unidad de Gestión de Aparato Digestivo, Hospital Universitario Virgen Macarena, España
| | | | - Raúl Perea Amarillo
- Unidad de Gestión Clínica Intercentros de Aparato , Hospital Universitario Virgen Macarena, España
| | | | - Ángel Caunedo Álvarez
- Unidad de Gestión Clínica de Aparato , Hospital Universitario Virgen Macarena , España
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Fiorino G, Gilardi D, Correale C, Furfaro F, Roda G, Loy L, Argollo M, Allocca M, Peyrin-Biroulet L, Danese S. Biosimilars of adalimumab: the upcoming challenge in IBD. Expert Opin Biol Ther 2019; 19:1023-1030. [DOI: 10.1080/14712598.2019.1564033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Gionata Fiorino
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Daniela Gilardi
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Carmen Correale
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Federica Furfaro
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Giulia Roda
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Laura Loy
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Marjorie Argollo
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Mariangela Allocca
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
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Gimeno-Gracia M, Gargallo-Puyuelo CJ, Gomollón F. Bioequivalence studies with anti-TNF biosimilars. Expert Opin Biol Ther 2018; 19:1031-1043. [PMID: 30574813 DOI: 10.1080/14712598.2019.1561851] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Introduction: Biosimilars, as defined by the European Medicines Agency, have been used in Europe since 2006. The landscape was considerably expanded when the first biosimilar of a monoclonal was approved and introduced in the European market. CT-P13 was developed by Celltrion as an infliximab biosimilar in 2013, not without controversy. As these complex molecules cannot be completely identical, some experts, clinicians, and even patients were skeptical regarding the real bioequivalence of the drugs. Currently, several new infliximab and adalimumab biosimilars are available or will reach the market in a few months. Areas covered: Our goal is to review, mainly from a clinical perspective, the available evidence for bioequivalence of anti-TNF biosimilars. We aim to take into account not only preclinical studies, mostly done for regulatory issues, but also data from clinical studies. Expert opinion: We can conclude that bioequivalence with originator is well demonstrated in those drugs which have followed European Medicines Agency regulatory pathways. Switching from originator to biosimilar appears safe for all indications. However, there are few data available for switching from one biosimilar to another, or for complete interchangeability. Prospective studies and strict pharmacovigilance are recommended.
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Affiliation(s)
- Mercedes Gimeno-Gracia
- Service of Pharmacy, Hospital Clínico Universitario "Lozano Blesa", IIS Aragón , Zaragoza , Spain
| | - Carla J Gargallo-Puyuelo
- Digestive Diseases Service, Hospital Clínico Universitario "Lozano Blesa", IIS Aragón, CIBEREHD , Zaragoza , Spain
| | - Fernando Gomollón
- Departamento de Medicina, Facultad de Medicina, Digestive Diseases Service, Hospital Clínico Universitario "Lozano Blesa", IIS Aragón, CIBEREHD , Zaragoza , Spain
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36
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Odinet JS, Day CE, Cruz JL, Heindel GA. The Biosimilar Nocebo Effect? A Systematic Review of Double-Blinded Versus Open-Label Studies. J Manag Care Spec Pharm 2018; 24:952-959. [PMID: 30247100 PMCID: PMC10398229 DOI: 10.18553/jmcp.2018.24.10.952] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Several authors have hypothesized that adverse drug events (ADEs) upon switching from reference biologics to biosimilar products are related to the nocebo effect. However, a thorough and current review of the existing literature has not been conducted. OBJECTIVE To evaluate if patient and/or physician knowledge of a switch from a reference biologic product to a biosimilar product was associated with an increase in ADEs likely to be susceptible to the nocebo effect. METHODS Studies reporting efficacy and safety outcomes of a switch from a reference product to a biosimilar product were reviewed. Biologics with FDA-approved biosimilars in the United States were considered for review, including adalimumab, bevacizumab, etanercept, and infliximab. Studies were identified by searching controlled vocabulary (e.g., MeSH terms) and keywords within MEDLINE (via PubMed) and Embase. Descriptive statistics were used to quantify subjective and objective complications in double-blinded and single-blinded or open-label studies. RESULTS Thirty-one trials including 3,271 patients were reviewed in the full analysis. Median discontinuation rates for any reason were 14.3% (range = 0.0-33.3) in open-label studies compared with 6.95% (range = 5.2-11.0) in double-blinded studies. Discontinuation rates for ADEs were 5.6% (range = 0.0-24.2) in open-label studies versus 3.1% (range = 2.0-5.2) in double-blinded studies, suggesting the nocebo effect does affect biosimilar adoption. Subgroup analyses of antidrug antibody (ADA) development and infusion reactions were similar between infliximab open-label and double-blinded studies. Discontinuation rates for any reason, for ADEs, and for lack of efficacy were generally higher in infliximab open-label trials compared with double-blinded trials. Etanercept biosimilar discontinuation rates for any reason were similar between study designs; however, incidences of injection site reactions and discontinuation rates for ADEs were higher in double-blinded compared with open-label study designs. CONCLUSIONS Current evidence is insufficient to confirm a biosimilar nocebo effect, although higher discontinuation rates in infliximab biosimilar open-label studies support this theory. Further studies are needed to evaluate the existence of a biosimilar nocebo effect. DISCLOSURES No outside funding supported this study. The authors have no conflicts of interest to disclose.
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Affiliation(s)
- Johlee S Odinet
- 1 Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill
| | - Chelsea E Day
- 1 Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill
| | - Jennifer L Cruz
- 1 Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill
| | - Gregory A Heindel
- 1 Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill
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Guerra Veloz MF, Argüelles-Arias F, Castro Laria L, Maldonado Pérez B, Benítez Roldan A, Perea Amarillo R, Merino Bohórquez V, Calleja MA, Caunedo Álvarez Á, Vilches Arenas Á. Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar (CT-P13) in patients with inflammatory bowel disease. World J Gastroenterol 2018; 24:5288-5296. [PMID: 30581277 PMCID: PMC6295832 DOI: 10.3748/wjg.v24.i46.5288] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 11/18/2018] [Accepted: 12/07/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Infliximab original has changed the natural history of inflammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited.
AIM To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD.
METHODS An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar.
RESULTS 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar.
CONCLUSION The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.
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Affiliation(s)
| | | | - Luisa Castro Laria
- Department of Gastroenterology, University Hospital Virgen Macarena, Seville 41007, Spain
| | - Belén Maldonado Pérez
- Department of Gastroenterology, University Hospital Virgen Macarena, Seville 41007, Spain
| | - Antonio Benítez Roldan
- Department of Gastroenterology, University Hospital Virgen Macarena, Seville 41007, Spain
| | - Raúl Perea Amarillo
- Department of Gastroenterology, University Hospital Virgen Macarena, Seville 41007, Spain
| | | | | | - Ángel Caunedo Álvarez
- Department of Gastroenterology, University Hospital Virgen Macarena, Seville 41007, Spain
| | - Ángel Vilches Arenas
- Preventive Medicine and Public Health, University Hospital Virgen Macarena, Seville 41007, Spain
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38
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Park SK, Hisamatsu T, Ran Z, Wei SC, Park DI. WITHDRAWN:Knowledge and viewpoints on biosimilar monoclonal antibodies from members of the Asian Organization of Crohn's and Colitis: comparison with European Crohn's and Colitis members. Intest Res 2018:ir.2018.00084. [PMID: 30419639 DOI: 10.5217/ir.2018.00084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 10/06/2018] [Indexed: 02/28/2024] Open
Abstract
Ahead of Print article withdrawn by publisher.
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Affiliation(s)
- Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tadakazu Hisamatsu
- Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Zhihua Ran
- Department of Gastroenterology, Shanghai Jiao Tong University, Shanghai, China
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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39
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Borman ZA, Côté-Daigneault J, Colombel JF. The risk for opportunistic infections in inflammatory bowel disease with biologics: an update. Expert Rev Gastroenterol Hepatol 2018; 12:1101-1108. [PMID: 30277409 DOI: 10.1080/17474124.2018.1530983] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Crohn's disease and Ulcerative Colitis are forms of inflammatory bowel disease (IBD), chronic diseases treated with medical and surgical therapy. Patients with IBD are treated with potent immunomodulatory agents, leading to immunosuppression, and the potential for opportunistic infections. In 2014, the ECCO guidelines were released to guide the prevention, diagnosis and treatment of a variety of these opportunistic infections. Since 2014, there have been a number of new agents released as well as a significant expansion in our knowledge of the safety profile of IBD medications. In this article, we review the literature after 2014 regarding opportunistic infections and updates on safety data. Areas covered: We review updates in immunomodulatory therapies for IBD and opportunistic infections since the 2014 ECCO guidelines were published. Expert commentary: The prevention, diagnosis, and treatment of opportunistic infections continue to evolve, as new drugs are approved, and the use of a combination of biologic agents are considered for therapy in clinical trials. What causes some patients to fail to respond to vaccination, or for others to develop severe infections, remains unclear. Improved risk stratification for opportunistic infections in IBD patients and updated ECCO 2014 guidelines would be of significant benefit.
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Affiliation(s)
- Zachary A Borman
- a The Henry D. Janowitz Division of Gastroenterology , One Gustave L. Levy Place , New York , NY , USA
| | - Justin Côté-Daigneault
- b Gastroenterology Service , Centre Hospitalier de l'Université de Montréal (CHUM) , Montreal , Quebec , Canada
| | - Jean-Frédéric Colombel
- a The Henry D. Janowitz Division of Gastroenterology , One Gustave L. Levy Place , New York , NY , USA
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40
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Paramsothy S, Rosenstein AK, Mehandru S, Colombel JF. The current state of the art for biological therapies and new small molecules in inflammatory bowel disease. Mucosal Immunol 2018; 11:1558-1570. [PMID: 29907872 PMCID: PMC6279599 DOI: 10.1038/s41385-018-0050-3] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 05/15/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023]
Abstract
The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.
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Affiliation(s)
- Sudarshan Paramsothy
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Adam K. Rosenstein
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA,PrIISM Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Saurabh Mehandru
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA,PrIISM Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Mayoral-Zavala A, Esquivel-Aguilar A, del Real-Calzada C, Gutiérrez-Grobe Y, Ramos-García J, Rocha-Ramírez J, Rojas-Illanes M, Rubio-Martínez B, Sánchez-Chávez X, Yamamoto-Furusho J. Update on biosimilars in inflammatory bowel disease: Position and recommendations in Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2018.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Mayoral-Zavala A, Esquivel-Aguilar A, Del Real-Calzada CM, Gutiérrez-Grobe Y, Ramos-García J, Rocha-Ramírez JL, Rojas-Illanes MF, Rubio-Martínez B, Sánchez-Chávez X, Yamamoto-Furusho JK. Update on biosimilars in inflammatory bowel disease: Position and recommendations in Mexico. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2018; 83:414-423. [PMID: 29685744 DOI: 10.1016/j.rgmx.2018.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 03/02/2018] [Accepted: 03/06/2018] [Indexed: 06/08/2023]
Abstract
The biotechnology-derived medicines known as biosimilars are defined as non-originator treatments that have demonstrated quality, efficacy, and safety comparable to the reference biologic drug. Clinical trials have shown that the infliximab biosimilar, CT-P13, and the candidates for the adalimumab biosimilars, ABP 501 and ZRC 3197, are not significantly different, with respect to efficacy and safety, from the originator drugs in patients with other autoimmune diseases. However, controversy has arisen over the use of biosimilars in inflammatory bowel disease, due to the incipient evidence not only in patients with no previous biotechnology treatment, but also in patients in remission, that could be switched to a biosimilar for non-medical reasons. The present review is the first critical analysis by different specialists in the area of gastroenterology on the use of biosimilars in inflammatory bowel disease, the evidence on interchangeability, the extrapolation of indications, efficacy, safety, immunogenicity, and the clinical impact of the Mexican health regulations. The aim of our review was to make the positioning and recommendations of these new therapeutic options known, given that they have a potential cost-benefit for both patients and healthcare institutions.
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Affiliation(s)
- A Mayoral-Zavala
- Departamento de Gastroenterología y Clínica de Intestino, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México.
| | - A Esquivel-Aguilar
- Subdirección de Farmacovigilancia, Asociación Farmacéutica Mexicana AC, Ciudad de México, México
| | - C M Del Real-Calzada
- Departamento de Gastroenterología y Clínica del Colon, Centro Médico Nacional La Raza, IMSS, Ciudad de México, México
| | - Y Gutiérrez-Grobe
- Clínica de Enfermedades Digestivas y Obesidad, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J Ramos-García
- Departamento de Gastroenterología y Clínica de Intestino, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | | | - M F Rojas-Illanes
- Servicio de Cirugía de Colon y Recto, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - B Rubio-Martínez
- Servicio de Cirugía de Colon y Recto, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - X Sánchez-Chávez
- Servicio de Gastroenterología y Endoscopia, Hospital Ángeles del Pedregal, Ciudad de México, México
| | - J K Yamamoto-Furusho
- Departamento de Gastroenterología, Clínica de Enfermedad Inflamatoria Intestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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Numan S, Faccin F. Non-medical Switching from Originator Tumor Necrosis Factor Inhibitors to Their Biosimilars: Systematic Review of Randomized Controlled Trials and Real-World Studies. Adv Ther 2018; 35:1295-1332. [PMID: 30084060 PMCID: PMC6133136 DOI: 10.1007/s12325-018-0742-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Indexed: 02/06/2023]
Abstract
Tumor necrosis factor (TNF) inhibitors are widely used biologics for the treatment of several chronic inflammatory diseases. The launch of anti-TNF biosimilars has introduced the possibility of non-medical switching between originator biologics and their biosimilars. However, the potential clinical and patient-reported consequences of non-medical switching remain largely unknown, as much of the evidence comes from poorly or uncontrolled real-world evidence (RWE) studies that often have an element of bias and nonstandardized outcome measures. To appropriately evaluate the safety, efficacy, and immunogenicity of non-medical switching from an originator to its biosimilar, we propose that seven key study design elements should be considered when assessing the existing evidence: studies should be (1) randomized and double-blind, (2) adequately controlled, and (3) adequately powered; include (4) multiple switching, (5) an assessment of immunogenicity, and (6) adequate follow-up duration; and (7) report individual patient-level outcomes. This systematic review assessed the robustness and consistency of the current non-medical switching evidence, with a focus on TNF inhibitors. A comprehensive literature search (January 2012-February 2018) identified 98 publications corresponding to 91 studies (17 randomized controlled trials and 74 RWE studies) describing non-medical switching from a TNF inhibitor originator to its biosimilar. When assessing the totality of this evidence, none of the non-medical switching studies conducted to date were found to use all seven of the key design elements, and the absence of these elements dilutes the robustness of the data. Furthermore, discontinuation rates varied widely among studies (0-87%), suggesting heterogeneity and inconclusiveness of the current efficacy, safety, and immunogenicity evidence, particularly at an individual patient level. Therefore, patients should not be indiscriminately switched from an originator TNF inhibitor to its biosimilar for non-medical reasons. Switching decisions should remain between the treating physicians and their patients and be made on a case-by-case basis, relying upon robust scientific evidence. FUNDING AbbVie.Plain Language Summary: Plain language summary available for this article.
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Kurti Z, Gonczi L, Lakatos PL. Progress with infliximab biosimilars for inflammatory bowel disease. Expert Opin Biol Ther 2018; 18:633-640. [PMID: 29688797 DOI: 10.1080/14712598.2018.1469620] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Biological therapies have revolutionized the treatment of inflammatory bowel diseases (IBD) in the last two decades. Though biological drugs are effective, their use is associated with high costs and access to biological agents varies among countries. As the patent for the reference products expired, the advent of biosimilar monoclonal antibodies has been expected. Biosimilars represent less expensive alternatives compared to the reference product. AREAS COVERED In this review, authors will review the literature on the clinical efficacy, safety and immunogenicity of current and future biosimilar infliximabs. Short- and medium-term data from real-life cohorts and from randomized-clinical trials in IBD demonstrated similar outcomes in terms of efficacy, safety and immunogenicity as the reference product for CT-P13. Switch data from the reference to the biosimilar product are also accumulating (including the NOR-SWITCH and the CT-P13 3.4 study). EXPERT OPINION The use of biosimilar infliximab in IBD is increasing worldwide. Its use may be associated with budget savings leading to better access to biological therapies and consequently improved health outcomes. Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching, and cross-switching among biosimilars in IBD patients.
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Affiliation(s)
- Zsuzsanna Kurti
- a First Department of Medicine , Semmelweis University , Budapest , Hungary
| | - Lorant Gonczi
- a First Department of Medicine , Semmelweis University , Budapest , Hungary
| | - Peter L Lakatos
- a First Department of Medicine , Semmelweis University , Budapest , Hungary
- b Division of Gastroenterology , McGill University Health Center , Montreal , QC , Canada
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Rackovsky O, Hirten R, Ungaro R, Colombel JF. Clinical updates on perianal fistulas in Crohn's disease. Expert Rev Gastroenterol Hepatol 2018; 12:597-605. [PMID: 29792734 DOI: 10.1080/17474124.2018.1480936] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Perianal fistulizing disease is an aggressive and debilitating phenotype of Crohn's disease (CD), representing a significant therapeutic challenge. New work has led to advancement in epidemiology and long-term outcomes of perianal disease. The range of therapeutic options continues to expand, including new biologic agents, biosimilars, and stem cell therapy. Areas covered: We discuss updates to all aspects of management of perianal disease, with a focus on the last 3 years of published data. Areas considered include new data on epidemiology and prognostication, medical and surgical therapy, and stem cell therapy. Expert commentary: The presence of perianal disease at CD diagnosis portends a significantly worse disease course. Patients with perianal disease require close monitoring to identify those who are at risk for worsening disease, suboptimal biologic drug levels, and signs of developing neoplasm. With the impending availability of local mesenchymal stem cell therapy, this becomes increasingly important as this therapy, although extremely promising, is thus far only effective in patients without proctitis.
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Affiliation(s)
- Ori Rackovsky
- a Department of Medicine, Division of Gastroenterology , Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai , New York , NY , USA
| | - Robert Hirten
- a Department of Medicine, Division of Gastroenterology , Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai , New York , NY , USA
| | - Ryan Ungaro
- a Department of Medicine, Division of Gastroenterology , Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai , New York , NY , USA
| | - Jean-Frederic Colombel
- a Department of Medicine, Division of Gastroenterology , Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai , New York , NY , USA
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Gisbert JP, Chaparro M. Switching from an originator anti-TNF to a biosimilar in patients with inflammatory bowel disease: Can it be recommended? A systematic review. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:389-405. [PMID: 29753532 DOI: 10.1016/j.gastrohep.2018.04.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 04/04/2018] [Accepted: 04/04/2018] [Indexed: 12/17/2022]
Abstract
AIM To review the effectiveness and safety of switching from an originator anti-TNF (Remicade®) to a biosimilar (CT-P13) in patients with inflammatory bowel disease (IBD). METHODS Electronic and manual search up to September 2017. RESULTS We identified 24 studies evaluating switching between Remicade® and CT-P13 in 1326 patients. Disease control (no worsening after switching) was confirmed in most of the patients (weighted mean, 88%; 95% CI=86-89%). No unexpected adverse effects were reported in any of the studies. CONCLUSION The risks of switching from Remicade® to a biosimilar seem to be purely theoretical and are not supported by the (still limited) real-world clinical practice experience. On the contrary, a steadily increasing number of publications have shown that there seem to be no safety or efficacy concerns about switching. Therefore, switching from originator to biosimilar infliximab in patients with IBD may be considered acceptable.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
| | - María Chaparro
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Scott FI, Lichtenstein GR. Biosimilars in the Treatment of Inflammatory Bowel Disease: Supporting Evidence in 2017. ACTA ACUST UNITED AC 2018; 16:147-164. [PMID: 29492747 DOI: 10.1007/s11938-018-0177-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Monoclonal antibodies targeting tumor necrosis factor-alpha, integrin molecules, and interleukin-12/23 have become backbone therapies for Crohn's disease and ulcerative colitis. While clinically effective, these biologic therapies come with significant expense, contributing to overall healthcare spending in the USA. Biosimilars have the potential to significantly reduce expenditures secondary to the use of biologic medications such as infliximab and adalimumab, though their complicated manufacturing process results in inherent differences in structure when compared to the originator compounds. In this article, we review the available literature regarding biosimilars in IBD. RECENT FINDINGS Several biosimilar agents to infliximab and adalimumab are currently FDA-approved, with many more currently in development. Initial clinical trials for approval have been conducted in one of the original indications for each originator biologic. There are growing data demonstrating similar clinical efficacy, immunogenicity, and safety of each of the approved infliximab and adalimumab biosimilars, both through indication extrapolation from other diseases such as rheumatoid arthritis and ankylosing spondylitis, as well observational data in patients with inflammatory bowel disease. Further research is ongoing regarding the efficacy and safety of substitution and interchangeability of biosimilars, as well as therapeutic drug monitoring for biosimilar agents. Research to date supports the utilization of reference biologics and biosimilars for new initiators, while additional data are being accrued regarding the interchangeability between these agents.
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Affiliation(s)
- Frank I Scott
- Crohn's and Colitis Center, Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, 1635 Aurora Court, Room 2.031, Mail Stop F735, Aurora, CO, 80045, USA.
| | - Gary R Lichtenstein
- Gastroenterology Division, Perelman School of Medicine, University of Pennsylvania, 7th Floor South Perelman Building, Room 753, 3400 Civic Center Boulevard, Philadelphia, PA, 19104-4283, USA
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McKinnon RA, Cook M, Liauw W, Marabani M, Marschner IC, Packer NH, Prins JB. Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review. BioDrugs 2018; 32:27-52. [PMID: 29344876 PMCID: PMC5814534 DOI: 10.1007/s40259-017-0256-z] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern. OBJECTIVES The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps. METHODS A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies. RESULTS The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups. CONCLUSIONS There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.
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Affiliation(s)
- Ross A McKinnon
- School of Medicine, Flinders University, Bedford Park, GPO Box 2100, Adelaide, SA, 5001, Australia.
| | - Matthew Cook
- John Curtin School of Medical Research, Australian National University and Canberra Hospital, Canberra, ACT, Australia
| | - Winston Liauw
- Cancer Care Centre, St George Hospital, Kogarah, Australia
- University of New South Wales, Kensington, NSW, Australia
| | | | - Ian C Marschner
- Department of Statistics, Macquarie University, North Ryde, Australia
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
| | - Nicolle H Packer
- Department of Chemistry and Biomolecular Sciences and ARC Centre of Nanoscale Biophotonics, Macquarie University, North Ryde, Australia
- Institute for Glycomics,, Griffith University, Southport, QLD, Australia
| | - Johannes B Prins
- Mater Research Institute, University of Queensland, Brisbane, QLD, Australia
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Ilias A, Gonczi L, Kurti Z, Lakatos PL. Biosimilars in ulcerative colitis: When and for who? Best Pract Res Clin Gastroenterol 2018; 32-33:35-42. [PMID: 30060937 DOI: 10.1016/j.bpg.2018.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 03/27/2018] [Accepted: 05/03/2018] [Indexed: 01/31/2023]
Abstract
The introduction of biological agents has revolutionized the management of ulcerative colitis (UC). Biosimilars are considered to be equivalent to the reference biologic products in terms of pharmacokinetic properties, clinical effectiveness and safety and have now been approved in inflammatory bowel diseases (IBD). CT-P13 was the first biosimilar to infliximab that obtained regulatory approval by the EMA and US FDA. Accumulating data on biosimilars led to an increased acceptance amongst practicing gastroenterologists and their use can be associated with a potential reduction in healthcare costs. This review discusses the current state of knowledge on biosimilar use in UC. Authors review the existing data on clinical efficacy, safety and immunogenicity of biosimilar infliximab and adalimumab agents. Emerging data suggests that switching from originator to biosimilar is safe for CT-P13 infliximab, however data on other biosimilars, multiple-switching, reverse-switching, or cross-switching between biosimilars is lacking. The pathway for interchangeability of biosimilars is different in the US and Europe and many aspects have yet to be clarified by federal regulators. Since the approval of the first biosimilar, the biosimilar concept seems to be successful and has led to an increased use of biosimilar drugs in the treatment of UC worldwide with a better access for patients to biologic. Real-world data from prospective observational studies for 'follow-on' biosimilars is needed to ensure that safety, efficacy and immunogenicity is comparable to the originator in IBD, and that switching from the originator or among biosimilars is a safe option.
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Affiliation(s)
- Akos Ilias
- Semmelweis University, First Department of Internal Medicine, Budapest, Hungary.
| | - Lorant Gonczi
- Semmelweis University, First Department of Internal Medicine, Budapest, Hungary.
| | - Zuszsanna Kurti
- Semmelweis University, First Department of Internal Medicine, Budapest, Hungary.
| | - Peter L Lakatos
- Semmelweis University, First Department of Internal Medicine, Budapest, Hungary; McGill University, Division of Gastroenterology, Montreal, Canada.
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Midha V, Mahajan R, Mehta V, Narang V, Singh A, Kaur K, Sood A. Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis. Intest Res 2018; 16:83-89. [PMID: 29422802 PMCID: PMC5797276 DOI: 10.5217/ir.2018.16.1.83] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 09/09/2017] [Accepted: 09/09/2017] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/AIMS Data on the efficacy and safety of the adalimumab biosimilar Exemptia are limited. METHODS Patients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital, India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing schedule of 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response and remission were assessed at week 8 using Mayo score. RESULTS A total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years) with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%]; left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporine and tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis. CONCLUSIONS The adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.
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Affiliation(s)
- Vandana Midha
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
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