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Bruni M, Lobefaro F, Pellegrini C, Mastrangelo M, Gualdi G, Esposito M, Antonetti P, De Sanctis P, Amerio P, Fargnoli MC. Psoriasis and cancer: the role of inflammation, immunosuppression, and cancer treatment. Expert Opin Biol Ther 2025; 25:395-411. [PMID: 40034077 DOI: 10.1080/14712598.2025.2471093] [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: 12/17/2024] [Revised: 02/10/2025] [Accepted: 02/19/2025] [Indexed: 03/05/2025]
Abstract
INTRODUCTION The relationship between psoriasis, immunomodulatory therapies, and the risk of malignancies is complex and still debated. The scarcity of evidence in this field makes clinicians hesitate to prescribe biological therapies for 'difficult-to-treat' patients. AREAS COVERED Based on a comprehensive MEDLINE/PUBMED search of articles published up to November 2024, this review synthesizes the current evidence on the association between psoriasis and cancer. This review specifically addresses four key aspects: the overall cancer risk in psoriatic patients, the potential role of cytokines involved in psoriasis pathogenesis in tumor development, the association between biological therapies and the incidence of new malignancies in this population, and the risk of cancer recurrence or progression in patients with a history of malignancy who are treated with biologics. EXPERT OPINION Biological therapies do not significantly elevate malignancy risk compared to non-biological treatments or the general population. Evidence is also reassuring for patients with prior malignancy, showing no tumor progression or recurrence. These findings support the timely use of biological treatments in 'difficult-to-treat' patients. Regular cancer screenings and risk-factor minimization should always be recommended for psoriatic patients undergoing immunomodulatory therapies. Multidisciplinary management involving oncologists is suggested, particularly for patients with active and advanced oncological disease.
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Affiliation(s)
- Manfredo Bruni
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Fabio Lobefaro
- Dermatology, Department of Medicine and Aging Science, University of Chieti-Pescara, Chieti, Italy
| | - Cristina Pellegrini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Mirco Mastrangelo
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giulio Gualdi
- Dermatology, Department of Medicine and Aging Science, University of Chieti-Pescara, Chieti, Italy
| | - Maria Esposito
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Paolo Antonetti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Paolo De Sanctis
- Dermatology, Department of Medicine and Aging Science, University of Chieti-Pescara, Chieti, Italy
| | - Paolo Amerio
- Dermatology, Department of Medicine and Aging Science, University of Chieti-Pescara, Chieti, Italy
| | - Maria Concetta Fargnoli
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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Okabayashi S, Itaya T, Yamazaki H, Yanai R, Isshiki M, Yamamoto Y. Estimating cancer risk in immune-mediated inflammatory diseases exposed to varying doses of tumour necrosis factor inhibitors. J Gastroenterol 2025; 60:285-293. [PMID: 39636325 DOI: 10.1007/s00535-024-02190-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 11/21/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND The safety profile of high doses of tumour necrosis factor inhibitors (TNFi) therapy for cancer risk in immune-mediated inflammatory diseases (IMIDs) remains uncertain. We evaluated the risk of cancer development in patients with IMIDs exposed to standard and high doses of TNFi compared with those never exposed to TNFi. METHODS A cohort study was conducted using the Japanese claims database encompassing over 4.6 million individuals from 2013 to 2021. The study included patients aged 16 years or older with new-onset IMIDs, such as inflammatory bowel disease, rheumatoid arthritis, or psoriasis, who had no cancer history. The subdistribution hazard ratios (SHR) for cancer risk in TNFi standard and high dose groups comparing with TNFi unexposed group were estimated using a Fine and Gray model that accounted for the competing risk of death unrelated to cancer. The high dose of TNFi was defined as either a dose escalation or shortening of the intervals during administrations from the standard dose treatment. RESULTS We identified a total of 42,006 patients with new-onset IMIDs (40,573 in TNFi unexposed, 876 in TNFi standard dose, and 557 in TNFi high dose) and 1211 (2.8%) patients developed cancer, yielding an incidence rate of 787.8 (739.9-828.1) per 100,000 person-years. Neither the standard nor high doses of TNFi significantly increased the cancer risk (TNFi standard dose vs. TNFi unexposed, adjusted SHR, 0.65 [0.40-1.08]; TNF high dose vs. TNFi unexposed, adjusted SHR, 1.12 [0.67-1.87]). CONCLUSIONS There is no association between varying doses of TNFi therapy and cancer risk in IMIDs.
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Affiliation(s)
- Shinji Okabayashi
- Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Takahiro Itaya
- Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Syogoin, Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan.
| | - Ryo Yanai
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Masaaki Isshiki
- IQVIA Solutions Japan G.K., 4-10-18 Takanawa, Minato-ku, Tokyo, 108-0074, Japan
| | - Yosuke Yamamoto
- Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
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Sakai H, Minami-Hori M, Kuwahara S. Malignancies in patients with psoriasis during and after biological therapy: A single-center experience. J Dermatol 2025; 52:383-386. [PMID: 39548820 DOI: 10.1111/1346-8138.17554] [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: 07/25/2024] [Revised: 10/02/2024] [Accepted: 11/04/2024] [Indexed: 11/18/2024]
Abstract
Over a 14-year period from 2010 to 2023, we treated 86 psoriasis patients with various biological agents at Asahikawa City Hospital, and 12 malignancies occurred in 11 of the patients. The numbers of malignancies by organ were as follows: four urogenital, three hematological, two gastrointestinal, one breast, one thyroid, and one lung. In two patients without cancer-related symptoms, elevated serum Krebs von den Lungen-6 levels led to the detection of intrahepatic cholangiocarcinoma or thyroid cancer, and they did not have interstitial lung disease. Dermatologists should be aware of the increased incidence of malignancy in patients with psoriasis requiring treatment with biologics.
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Affiliation(s)
- Hiroyuki Sakai
- Division of Dermatology, Asahikawa City Hospital, Asahikawa, Japan
| | | | - Shiro Kuwahara
- Division of Dermatology, Asahikawa City Hospital, Asahikawa, Japan
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Zhao Y, Li Z, Zhang K, Wang N. Detection of risk signals for ustekinumab in the real world using the FDA Adverse Event Reporting System (FAERS). Expert Opin Drug Saf 2024:1-7. [PMID: 39711190 DOI: 10.1080/14740338.2024.2446409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/07/2024] [Accepted: 10/18/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Ustekinumab is a fully human interleukin-12/23 (p40) inhibitor used to treat immune-mediated diseases. However, the limitations of clinical trials and the expanding target population necessitate an update on the ustekinumab-associated adverse events (AEs). We conducted signal mining for ustekinumab-related AEs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS AE reports were collected from 2009 Q3 to 2024 Q1. Four disproportionality analysis algorithms - reporting odds ratio, medicines and healthcare products regulatory agency, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker - were used to quantify the signals of ustekinumab. RESULTS During this period 69,345 AE reports associated with ustekinumab were collected, and ustekinumab was identified as the primary suspect. Overall, 319 signals involving 15 system organ classes were identified, and 111 signals had a medium or strong value for IC025. Of them, 67 were classified as important medical events. Squamous cell carcinoma, pertussis, vulval abscess, breast abscess, and fistula exhibited higher signal intensities. CONCLUSIONS Our study identified the risk signals for ustekinumab using real-world data and provides further evidence to support its rational use. Due to the limitations of FAERS, further studies are warranted to verify these findings.
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Affiliation(s)
- Yi Zhao
- Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zelin Li
- Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kanghuai Zhang
- Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Na Wang
- Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Fanizzi F, Allocca M, Fiorino G, Zilli A, Furfaro F, Parigi TL, Peyrin-Biroulet L, Danese S, D’Amico F. Raising the bar in ulcerative colitis management. Therap Adv Gastroenterol 2024; 17:17562848241273066. [PMID: 39600566 PMCID: PMC11589388 DOI: 10.1177/17562848241273066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 07/17/2024] [Indexed: 11/29/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by growing incidence and prevalence around the world in the last few decades. The range of available existing treatment and strategies for its management is being implemented. Given the introduction of newly developed molecules and the lack of specific guidelines, drug positioning may represent a tough clinical challenge. UC management is mostly medical, and it has been shifting toward a more personalized approach with the aim to create a tailored strategy depending on the patient's profile. A treat-to target strategy seems to be the best approach to reach disease control as it allows to carry out therapeutic choices based on objective and specific parameters: histological, ultrasonographic, and molecular targets may add to the already used clinical, endoscopic, and biochemical targets. In addition, dual-targeted therapy has emerged as an attractive therapeutic strategy for patients not achieving remission. This review aims to provide an overview of the available strategies to raise the bar in UC.
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Affiliation(s)
- Fabrizio Fanizzi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Gionata Fiorino
- Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, Rome, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré—Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Via Olgettina 60, Milan 20132, Italy
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Tatovic D, Marwaha A, Taylor P, Hanna SJ, Carter K, Cheung WY, Luzio S, Dunseath G, Hutchings HA, Holland G, Hiles S, Fegan G, Williams E, Yang JHM, Domingo-Vila C, Pollock E, Wadud M, Ward-Hartstonge K, Marques-Jones S, Bowen-Morris J, Stenson R, Levings MK, Gregory JW, Tree TIM, Dayan C. Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial. Nat Med 2024; 30:2657-2666. [PMID: 39079992 PMCID: PMC11405276 DOI: 10.1038/s41591-024-03115-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 06/05/2024] [Indexed: 09/18/2024]
Abstract
Immunotherapy targeting the autoimmune process in type 1 diabetes (T1D) can delay the loss of β-cells but needs to have minimal adverse effects to be an adjunct to insulin in the management of T1D. Ustekinumab binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, targeting development of T helper 1 cells and T helper 17 cells (TH1 and TH17 cells) implicated in the pathogenesis of T1D. We conducted a double-blind, randomized controlled trial of ustekinumab in 72 adolescents aged 12-18 years with recent-onset T1D. Treatment was well tolerated with no increase in adverse events. At 12 months, β-cell function, measured by stimulated C-peptide, was 49% higher in the intervention group (P = 0.02), meeting the prespecified primary outcome. Preservation of C-peptide correlated with the reduction of T helper cells co-secreting IL-17A and interferon-γ (TH17.1 cells, P = 0.04) and, in particular, with the reduction in a subset of TH17.1 cells co-expressing IL-2 and granulocyte-macrophage colony-stimulating factor (IL-2+ GM-CSF+ TH17.1 cells, P = 0.04). A significant fall in β-cell-targeted (proinsulin-specific) IL-17A-secreting T cells was also seen (P = 0.0003). Although exploratory, our data suggest a role for an activated subset of TH17.1 cells in T1D that can be targeted with minimal adverse effects to reduce C-peptide loss, which requires confirmation in a larger study. (International Standard Randomised Controlled Trial Number Registry: ISRCTN 14274380).
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Affiliation(s)
- Danijela Tatovic
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
| | | | - Peter Taylor
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Stephanie J Hanna
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Kym Carter
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | - W Y Cheung
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | - Steve Luzio
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | - Gareth Dunseath
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | | | - Gail Holland
- Swansea Trials Unit, Swansea University Medical School, Swansea, UK
| | - Steve Hiles
- Swansea Trials Unit, Swansea University Medical School, Swansea, UK
| | - Greg Fegan
- Swansea Trials Unit, Swansea University Medical School, Swansea, UK
| | - Evangelia Williams
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Jennie H M Yang
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Clara Domingo-Vila
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Emily Pollock
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Muntaha Wadud
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Kirsten Ward-Hartstonge
- BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Jane Bowen-Morris
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Rachel Stenson
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Megan K Levings
- BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | - John W Gregory
- Division of Population Medicine, Cardiff University School of Medicine, Cardiff, UK
| | - Timothy I M Tree
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Colin Dayan
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
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Wride AM, Chen GF, Spaulding SL, Tkachenko E, Cohen JM. Biologics for Psoriasis. Dermatol Clin 2024; 42:339-355. [PMID: 38796266 DOI: 10.1016/j.det.2024.02.001] [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] [Indexed: 05/28/2024]
Abstract
Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors.
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Affiliation(s)
- Anthony Mitchel Wride
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Gloria F Chen
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Sarah L Spaulding
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Elizabeth Tkachenko
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Jeffrey M Cohen
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA.
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Moon W, Park JJ. [Risks of Cancer Associated with Therapeutic Drugs for Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:233-242. [PMID: 38918036 DOI: 10.4166/kjg.2024.053] [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: 06/03/2024] [Revised: 06/21/2024] [Accepted: 06/21/2024] [Indexed: 06/27/2024]
Abstract
Crohn's disease and ulcerative colitis are lifelong chronic inflammatory conditions, with many patients requiring ongoing immunomodulatory drug therapy for maintenance treatment. Recent therapeutic goals in inflammatory bowel disease (IBD) are not only aimed at symptomatic remission but also at achieving mucosal healing to improve the natural course of the disease. In this context, therapeutic approaches are being applied in clinical settings that involve early and appropriate use of drugs, such as immunomodulators or biologics, that have the potential to induce healing of the inflamed intestine before irreversible intestinal damage occurs. All drugs that continuously control intestinal inflammation in IBD can heal the mucosa and potentially reduce the incidence of colitis-associated bowel cancer; however, the continuous use of immunosuppressants can potentially increase the risk of malignancies. The safety issues of the drugs used in clinical practice are partly confirmed during their development processes or shortly after initial marketing, but in other cases, they are estimated through post-marketing case reports or epidemiological studies, sometimes decades after drug approval. This review explores the risks associated with malignancies related to the treatment of IBD, focusing on drugs currently approved in Republic of Korea.
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Affiliation(s)
- Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Mateu-Arrom L, Puig L. Choosing the right biologic treatment for moderate-to-severe plaque psoriasis: the impact of comorbidities. Expert Rev Clin Pharmacol 2024; 17:363-379. [PMID: 38603464 DOI: 10.1080/17512433.2024.2340552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/01/2024] [Indexed: 04/13/2024]
Abstract
INTRODUCTION Psoriasis is a chronic inflammatory skin disease often associated with several comorbidities, such as psoriatic arthritis, inflammatory bowel disease, obesity, diabetes mellitus or cardiovascular diseases, infections, or cancer, among others. With the progressive aging of the population, a growing number of patients with psoriasis can be expected to present multiple comorbidities. Currently, there is a wide range of biological treatments available for moderate to severe psoriasis, including tumor necrosis alpha (TNF) inhibitors, IL12/23 inhibitor, IL17 inhibitors, and IL23 inhibitors. AREAS COVERED This review aims to describe the specific characteristics of these drugs in relation to psoriasis comorbidities, in order to facilitate decision-making in clinical practice. EXPERT OPINION Some of the biological treatments can influence comorbidities, in some cases even improving them. Therefore, comorbidities are a key factor when deciding on one biological treatment over another. The development of new drugs is expanding the therapeutic arsenal for psoriasis. A high level of expertise in the field with a detailed knowledge of the characteristics of every drug is imperative to provide personalized medicine.
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Affiliation(s)
- Laura Mateu-Arrom
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Lluis Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain
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10
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Sevdem GA, Ozlem KS, Nazan Y, Nahide O. Does the risk of basal cell carcinoma increase in patients with psoriasis under treatment? PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2024; 40:e12956. [PMID: 38404169 DOI: 10.1111/phpp.12956] [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: 12/05/2023] [Revised: 01/23/2024] [Accepted: 02/06/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND Psoriasis is a common, chronic, inflammatory disease. Although it mainly affects the skin, it has been associated with a large number of comorbidities. In addition to comorbidities such as depression and psoriatic arthritis, it is known that there is an increased prevalence of cancer in psoriasis patients. Skin cancers, particularly squamous cell carcinoma, have been associated with psoriasis. However, basal cell carcinoma data are limited. METHODS 346 psoriasis patients and 306 individuals were selected as the control group. There were no differences between the patient and control groups in terms of age and gender. The mean age of the psoriasis patients was 49.9 ± 15.8 years and the control group was 49.4 ± 13.4 years. Sociodemographic data of the patients were recorded. Pharmacological agents used in the treatment of psoriasis were included in the analysis. Disease severity was assessed by the psoriasis area severity index (PASI). In the physical examination of the patients, biopsies were taken from lesions suspicious for BCC. BCC diagnosis was made by histopathologically. RESULTS The frequency of BCC was higher in psoriasis patients than in the control group (6.6% vs. 2.9%, p < .001). Advanced age (p < .001), smoking (p = .003), and arthritis (p < .001) were associated with BCC in psoriasis patients. However, there was no relationship between PASI and BCC (p = .142). Among the psoriasis treatments, only UV therapy was associated with BCC (p = .038). The frequency of PUVA (p < .001) and number of PUVA session (p = .010) was higher in psoriasis patients with BCC rather than NB-UVB. CONCLUSION The frequency of BCC is increased in psoriasis patients. Psoriasis is associated with an increased risk of BCC, especially when treated with PUVA therapy for a long time.
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Affiliation(s)
| | | | - Yilmaz Nazan
- Bezmialem Vakif University, Fatih/İstanbul, Turkey
| | - Onsun Nahide
- Bezmialem Vakif University, Fatih/İstanbul, Turkey
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Imafuku S, Okubo Y, Tada Y, Ohtsuki M, Colston E, Napoli A, Shao Y, Banerjee S, Morita A. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in Japanese patients with moderate to severe plaque, erythrodermic, or generalized pustular psoriasis: Efficacy and safety results from an open-label, phase 3 trial. J Dermatol 2024; 51:365-379. [PMID: 38268101 PMCID: PMC11483964 DOI: 10.1111/1346-8138.17074] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 11/01/2023] [Accepted: 11/25/2023] [Indexed: 01/26/2024]
Abstract
Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in Japan for adult patients with plaque (PP), generalized pustular (GPP), and erythrodermic (EP) psoriasis who have had an inadequate response to conventional systemic therapies. This approval is based on results from the global phase 3 POETYK PSO-1 and PSO-2 trials in which deucravacitinib was associated with significantly improved efficacy outcomes compared with placebo in adults with moderate to severe plaque psoriasis, and results described here from POETYK PSO-4, an open-label, single-arm, phase 3 trial (NCT03924427), which evaluated the efficacy and safety of deucravacitinib 6 mg once daily in adult Japanese patients with PP, GPP, or EP. The coprimary endpoints were the proportion of patients achieving a ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) with at least a two-point improvement from baseline at week 16. Nonresponder imputation was used for missing data. Efficacy responses, adverse events (AEs), and serious AEs (SAEs) were recorded for up to 52 weeks. Seventy-four patients were treated (PP, n = 63; GPP, n = 3; EP, n = 8). At week 16, 76.2%, 66.7%, and 37.5% of patients with PP, GPP, and EP, respectively, had achieved PASI 75, and 82.5%, 0.0%, and 50.0% had achieved sPGA 0/1. Responses were overall maintained through week 52. AEs occurred in 74.6% of patients with PP, 100% of patients with GPP, and 87.5% of patients with EP. The most common AEs were nasopharyngitis and acne. Rates of SAEs and discontinuations were low. There were no deaths. Deucravacitinib was effective and well tolerated in Japanese patients with moderate to severe PP and in a limited number of patients with GPP or EP.
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Affiliation(s)
- Shinichi Imafuku
- Department of DermatologyFukuoka University Faculty of MedicineFukuokaJapan
| | - Yukari Okubo
- Department of DermatologyTokyo Medical UniversityTokyoJapan
| | - Yayoi Tada
- Department of DermatologyTeikyo University School of MedicineTokyoJapan
| | | | | | | | | | | | - Akimichi Morita
- Department of Geriatrics and Environmental DermatologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
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Strober B, Coates LC, Lebwohl MG, Deodhar A, Leibowitz E, Rowland K, Kollmeier AP, Miller M, Wang Y, Li S, Chakravarty SD, Chan D, Shawi M, Yang YW, Thaҫi D, Rahman P. Long-Term Safety of Guselkumab in Patients with Psoriatic Disease: An Integrated Analysis of Eleven Phase II/III Clinical Studies in Psoriasis and Psoriatic Arthritis. Drug Saf 2024; 47:39-57. [PMID: 37906417 PMCID: PMC10764399 DOI: 10.1007/s40264-023-01361-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2023] [Indexed: 11/02/2023]
Abstract
INTRODUCTION The benefit/risk profiles of biologics can be affected by comorbidities, certain demographic characteristics, and concomitant medications; therefore, it is important to evaluate the long-term safety profiles of biologics across broad patient populations. Guselkumab was well tolerated and efficacious across individual pivotal clinical studies in adults with moderate-to-severe psoriasis and/or active psoriatic arthritis (PsA). OBJECTIVES The objective of the current analysis was to evaluate guselkumab safety in a large population of patients with psoriatic disease by pooling adverse event (AE) data from 11 phase II/III studies (seven in psoriasis; four in PsA). METHODS Guselkumab was generally administered as 100 mg subcutaneous injections at Week 0, Week 4, then every 8 weeks (Q8W) in psoriasis studies and at Week 0, Week 4, then every 4 weeks (Q4W) or Q8W in PsA studies. Safety data were summarized for the placebo-controlled period (Weeks 0-16 in psoriasis; Weeks 0-24 in PsA) and through the end of the reporting period (up to 5 years in psoriasis; up to 2 years in PsA). Using the integrated data, incidence rates of key AEs were determined post hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PYs). AE rates were also determined in subgroups of patients defined by sex, age, body mass index (BMI), and prior biologic use. RESULTS During the placebo-controlled period, 1061 patients received placebo (395 PYs) and 2257 received guselkumab (856 PYs). Through the end of the reporting period, 4399 guselkumab-treated patients contributed 10,787 PYs of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of AEs were 281 versus 272/100 PYs, and infections were 76.0 versus 72.2/100 PYs. Rates of serious AEs (5.6 vs. 7.8/100 PYs), AEs leading to discontinuation (4.9 vs. 6.6/100 PYs), serious infections (1.0 vs. 2.3/100 PYs), malignancy (0.59 vs. 0.25 patients/100 PYs), and major adverse cardiovascular events (MACE; 0.35 vs. 0.25/100 PYs) were low and comparable between guselkumab and placebo. Among guselkumab-treated patients, safety event rates through the end of the reporting period were numerically lower than or comparable with rates observed during the placebo-controlled period: AEs, 164/100 PYs; infections, 61.2/100 PYs; serious AEs, 5.4/100 PYs; AEs leading to discontinuation, 1.8/100 PYs; serious infections, 1.0/100 PYs; malignancy, 0.6/100 PYs; and MACE, 0.3/100 PYs. No AEs of Crohn's disease, ulcerative colitis, or active tuberculosis were reported among guselkumab-treated patients. In the psoriasis studies, no opportunistic infections were reported among guselkumab-treated patients. Three AEs of opportunistic infections were reported in guselkumab-treated patients with PsA (0.14/100 PYs; all after Week 52 in DISCOVER-2). AE rates were largely consistent across subgroups of guselkumab-treated patients defined by sex, age, BMI, and prior biologic use. CONCLUSIONS In this analysis of 4399 guselkumab-treated patients with psoriatic disease followed for 10,787 PYs, guselkumab had a favorable AE profile. AE rates were similar between guselkumab- and placebo-treated patients and were consistent throughout long-term guselkumab treatment and across broad subgroups of patients with psoriatic disease. CLINICAL TRIALS REGISTRATIONS Clinicaltrials.gov identifiers: NCT01483599, NCT02207231, NCT02207244, NCT02203032, NCT02905331, NCT03090100, NCT02325219, NCT02319759, NCT03162796, NCT03158285, and NCT03796858.
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Affiliation(s)
- Bruce Strober
- Yale University, New Haven, CT, USA.
- Central Connecticut Dermatology Research, Cromwell, CT, USA.
| | - Laura C Coates
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Mark G Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Atul Deodhar
- Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA
| | | | | | | | - Megan Miller
- Janssen Research & Development, LLC, Spring House, PA, USA
| | - Yanli Wang
- Janssen Research & Development, LLC, Spring House, PA, USA
| | - Shu Li
- Janssen Research & Development, LLC, Spring House, PA, USA
| | - Soumya D Chakravarty
- Janssen Scientific Affairs, LLC, Horsham, PA, USA
- Drexel University College of Medicine, Philadelphia, PA, USA
| | - Daphne Chan
- Janssen Scientific Affairs, LLC, Horsham, PA, USA
| | - May Shawi
- Immunology, Janssen Research & Development, LLC, Titusville, NJ, USA
| | - Ya-Wen Yang
- Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, USA
| | - Diamant Thaҫi
- Institute and Comprehensive Center for Inflammatory Medicine, University of Luebeck, Luebeck, Germany
| | - Proton Rahman
- Division of Rheumatology, Craig L. Dobbin Genetics Research Centre, Discipline of Medicine, Memorial University of Newfoundland, St John's, NL, Canada
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13
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Davis MS, Spencer RK, Johnson CE, Elhage KG, Jin JQ, Hakimi M, Bhutani T, Liao W. Risk of Cutaneous T Cell Lymphoma with Psoriasis Biologic Therapies. Dermatol Ther (Heidelb) 2024; 14:15-30. [PMID: 38043065 PMCID: PMC10828324 DOI: 10.1007/s13555-023-01074-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 11/13/2023] [Indexed: 12/05/2023] Open
Abstract
BACKGROUND The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. METHODS The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. RESULTS Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. CONCLUSION Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use.
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Affiliation(s)
- Mitchell S Davis
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
| | - Riley K Spencer
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
- Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Chandler E Johnson
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
- Medical College of Georgia, Augusta, GA, USA
| | - Kareem G Elhage
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
| | - Joy Q Jin
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
- School of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Marwa Hakimi
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
| | - Tina Bhutani
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA
| | - Wilson Liao
- Department of Dermatology, University of California San Francisco, Floor 04, Room N426, 2340 Sutter Street, Box 0808, San Francisco, CA, 94115, USA.
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14
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Krzysztofik M, Brzewski P, Cuber P, Kacprzyk A, Kulbat A, Richter K, Wojewoda T, Wysocki WM. Risk of Melanoma and Non-Melanoma Skin Cancer in Patients with Psoriasis and Psoriatic Arthritis Treated with Targeted Therapies: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel) 2023; 17:14. [PMID: 38276003 PMCID: PMC10820691 DOI: 10.3390/ph17010014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 01/27/2024] Open
Abstract
Targeted therapies represent major advancements in the treatment of chronic skin conditions such as psoriasis. While previous studies have shown an increased risk of melanoma and non-melanoma skin cancer (NMSC) in patients receiving TNF-α inhibitors, the risks associated with newer biologics (IL-12/23 inhibitors, IL-23 inhibitors, IL-17 inhibitors) and Janus kinase (JAK) inhibitors remain less known. Using a systematic and meta-analytical approach, we aimed to summarize the currently available literature concerning skin cancer risk in patients treated with targeted therapies. The MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to find studies reporting the incidence rates (IR) of melanoma and NMSC in patients with psoriasis and psoriatic arthritis treated with biologics or JAK inhibitors. Nineteen studies were included in the analysis with a total of 13,739 patients. The overall IR of melanoma was 0.08 (95% CI, 0.05-0.15) events per 100 PYs and the overall IR of NMSC was 0.45 (95% CI, 0.33-0.61) events per 100 PYs. The IRs of melanoma were comparable across patients treated with IL-17 inhibitors, IL-23 inhibitors, and JAK inhibitors, while the IRs of NMSC were higher in patients treated with JAK inhibitors than in those treated with biologics. Prospective, long-term cohort studies are required to reliably assess the risks associated with novel targeted therapies.
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Affiliation(s)
- Marta Krzysztofik
- Department of Dermatology and Venereology, Stefan Zeromski Municipal Hospital, 31-913 Krakow, Poland
| | - Paweł Brzewski
- Department of Dermatology and Venereology, Stefan Zeromski Municipal Hospital, 31-913 Krakow, Poland
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland (W.M.W.)
| | - Przemysław Cuber
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland (W.M.W.)
- Department of Oncological Surgery, 5th Military Clinical Hospital in Kraków, 30-901 Krakow, Poland
| | - Artur Kacprzyk
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-530 Krakow, Poland
| | - Aleksandra Kulbat
- Department of Oncological Surgery, 5th Military Clinical Hospital in Kraków, 30-901 Krakow, Poland
| | - Karolina Richter
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland (W.M.W.)
| | - Tomasz Wojewoda
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland (W.M.W.)
- Department of Oncological Surgery, 5th Military Clinical Hospital in Kraków, 30-901 Krakow, Poland
| | - Wojciech M. Wysocki
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland (W.M.W.)
- Department of Oncological Surgery, 5th Military Clinical Hospital in Kraków, 30-901 Krakow, Poland
- National Institute of Oncology, Maria Skłodowska-Curie Memorial, 02-781 Warsaw, Poland
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15
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Wu S, Xu Y, Yang L, Guo L, Jiang X. Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Front Immunol 2023; 14:1294416. [PMID: 38106423 PMCID: PMC10721978 DOI: 10.3389/fimmu.2023.1294416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/10/2023] [Indexed: 12/19/2023] Open
Abstract
The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and Candida infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of Candida infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and Candida infection with IL-17 inhibitors. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.
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Affiliation(s)
- Shuwei Wu
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yuanyuan Xu
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Lihua Yang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Linghong Guo
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Tianfu Jincheng Laboratory & Institute of Future Medical Innovation, City of Future Medicine, Chengdu, China
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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16
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Gu SL, Nath S, Markova A. Safety of Immunomodulatory Systemic Therapies Used in the Management of Immune-Related Cutaneous Adverse Events. Pharmaceuticals (Basel) 2023; 16:1610. [PMID: 38004475 PMCID: PMC10674388 DOI: 10.3390/ph16111610] [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: 10/03/2023] [Revised: 11/08/2023] [Accepted: 11/11/2023] [Indexed: 11/26/2023] Open
Abstract
Immune-related cutaneous adverse events (ircAEs) commonly occur in patients on treatment with immune checkpoint inhibitors and can significantly reduce patient quality of life. These are often treated with immunomodulatory agents, including glucocorticoids, immunosuppressants, and biologics. While often effective at managing symptoms, these therapies can cause several adverse events which may limit their use. In addition, immunomodulatory agents should be used with particular caution in patients receiving immunotherapy, as the efficacy of the oncologic regimen may potentially be undermined. In this review, we summarize the safety of systemic therapies that are used in the management of ircAEs, with a particular focus on the resultant risk of secondary tumor progression in patients with active cancer.
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Affiliation(s)
- Stephanie L. Gu
- Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Sandy Nath
- Urgent Care Service, Memorial Sloan Kettering Cancer, New York, NY 10065, USA
| | - Alina Markova
- Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Department of Dermatology, Weill Cornell Medical College, New York, NY 10065, USA
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17
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Calapai F, Mannucci C, Cardia L, Currò M, Calapai G, Esposito E, Ammendolia I. Response to "Evaluating Adverse Events in Databases". Pharmacol Res Perspect 2023; 11:e01127. [PMID: 37589310 PMCID: PMC10433452 DOI: 10.1002/prp2.1127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 08/04/2023] [Indexed: 08/18/2023] Open
Affiliation(s)
- Fabrizio Calapai
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
- Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
| | - Carmen Mannucci
- Department of Biomedical and Dental Sciences and Morphological and Functional ImagingUniversity of MessinaMessinaItaly
| | - Luigi Cardia
- Department of Human Pathology of Adult and Childhood “Gaetano Barresi”University of MessinaMessinaItaly
| | - Mariaconcetta Currò
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
| | - Gioacchino Calapai
- Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
| | - Emanuela Esposito
- Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
| | - Ilaria Ammendolia
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
- Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
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18
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Lovell K, Feldman SR. Evaluating adverse events in databases. Pharmacol Res Perspect 2023; 11:e01129. [PMID: 37589317 PMCID: PMC10433453 DOI: 10.1002/prp2.1129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 07/23/2023] [Indexed: 08/18/2023] Open
Affiliation(s)
- Katie Lovell
- Department of Dermatology, Center for Dermatology ResearchWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Steven R. Feldman
- Department of Dermatology, Center for Dermatology ResearchWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
- Department of DermatologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
- Department of PathologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
- Department of Social Sciences & Health PolicyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
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19
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Zhang X, Rosh JR. Safety Summary of Pediatric Inflammatory Bowel Disease Therapies. Gastroenterol Clin North Am 2023; 52:535-548. [PMID: 37543398 DOI: 10.1016/j.gtc.2023.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2023]
Abstract
Therapeutic options for the treatment of pediatric inflammatory bowel disease include aminosalicylates, enteral nutrition, corticosteroids, immunomodulators, biologics, and emerging small molecule agents. Infectious risk due to systemic immunosuppression should be mitigated by appropriate screening before therapy initiation. Rare but serious malignancies have been associated with thiopurine use alone and in combination with anti-tumor necrosis factor agents, often in the setting of a primary Epstein-Barr virus infection. Potential agent-specific adverse events such as cytopenias, hepatotoxicity, and nephrotoxicity warrant regular clinical and laboratory monitoring.
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Affiliation(s)
- Xiaoyi Zhang
- Pediatric Gastroenterology, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Indiana University, 705 Riley Hospital Drive, ROC 4210, Indianapolis, IN 46202, USA. https://twitter.com/xtzhang
| | - Joel R Rosh
- Pediatric Gastroenterology, Division of Pediatric Gastroenterology, Liver Disease, and Nutrition, Cohen Children's Medical Center of New York, 1991 Marcus Avenue, Suite M100, Lake Success, NY 11042, USA.
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20
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Finnegan P, Ahmad K, Sadlier M, Lynch M. A retrospective review of the management of patients following a malignancy diagnosis on biologic therapies for the treatment of dermatological disorders. JAAD Case Rep 2023; 39:81-87. [PMID: 37664445 PMCID: PMC10468322 DOI: 10.1016/j.jdcr.2023.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023] Open
Affiliation(s)
- Paula Finnegan
- Department of Dermatology, University Hospital Limerick, Dooradoyle, Limerick, Ireland
| | - Kashif Ahmad
- Department of Dermatology, University Hospital Limerick, Dooradoyle, Limerick, Ireland
| | - Muriel Sadlier
- Department of Dermatology, University Hospital Limerick, Dooradoyle, Limerick, Ireland
| | - Maeve Lynch
- Department of Dermatology, University Hospital Limerick, Dooradoyle, Limerick, Ireland
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Verstockt B, Salas A, Sands BE, Abraham C, Leibovitzh H, Neurath MF, Vande Casteele N. IL-12 and IL-23 pathway inhibition in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2023; 20:433-446. [PMID: 37069321 PMCID: PMC10958371 DOI: 10.1038/s41575-023-00768-1] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/09/2023] [Indexed: 04/19/2023]
Abstract
Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn's disease and ulcerative colitis.
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Affiliation(s)
- Bram Verstockt
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
- KU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium
| | - Azucena Salas
- Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Clara Abraham
- Department of Medicine, Yale University, New Haven, CT, USA
| | - Haim Leibovitzh
- Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Markus F Neurath
- Department of Medicine 1, University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie DZI, University Erlangen-Nürnberg, Erlangen, Germany
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22
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Damiani G, Amerio P, Bardazzi F, Carrera CG, Conti A, Cusano F, Dapavo P, DeSimone C, El Hachem M, Fabbrocini G, Gisondi P, Loconsole F, Micali G, Neri I, Parodi A, Piaserico S, Romanelli M, Stingeni L, Pigatto PDM. Real-World Experience of Methotrexate in the Treatment of Skin Diseases: an Italian Delphi Consensus. Dermatol Ther (Heidelb) 2023:10.1007/s13555-023-00930-2. [PMID: 37210684 DOI: 10.1007/s13555-023-00930-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 04/17/2023] [Indexed: 05/22/2023] Open
Abstract
BACKGROUND After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology. OBJECTIVES To provide guidance for clinicians in daily practice for areas in which there is limited guidance. METHODS A Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings. RESULTS Consensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements. CONCLUSIONS In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients' risk factors and carry out proper monitoring during the course of treatment.
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Affiliation(s)
- Giovanni Damiani
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
- Italian Center of Precisione Medicine and Chronic Inflammation, University of Milan, Milan, Italy.
- UOC Dermatology, Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi, 4, 20161, Milan, Italy.
| | - Paolo Amerio
- Dermatologic Clinic, Department of Medicine and Aging Science, University "G. d'Annunzio", Chieti-Pescara, Italy
| | - Federico Bardazzi
- Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Carlo G Carrera
- Fondazione Cà Granda IRCCS Maggiore Policlinico Hospital, Milan, Italy
| | - Andrea Conti
- Dermatology Unit, Ospedale Infermi di Rimini, AUSL Romagna, Rimini, Italy
| | | | - Paolo Dapavo
- Dermatology Clinic, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Clara DeSimone
- DermatologiaDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
| | - May El Hachem
- Dermatology Unit and Genodermatosis Research Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Paolo Gisondi
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy
| | - Francesco Loconsole
- Department of Biomedical Sciences and Human Oncology, Section of Dermatology, University of Bari, Bari, Italy
| | | | - Iria Neri
- Dermatology, Sant'Orsola-Malpighi Polyclinic University Hospital-IRCCS, University of Bologna, Bologna, Italy
| | - Aurora Parodi
- Dermatology Clinic, DISSAL, Polyclinic Hospital San Martino-IRCCS, University of Genoa, Genoa, Italy
| | - Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | | | - Luca Stingeni
- Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Paolo D M Pigatto
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
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23
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Jedlowski PM. Association of Nonmelanoma Skin Cancers, Melanoma, and Merkel Cell Carcinoma with Dermatologic Medications: A Case-Control Pharmacovigilance Study of the FDA Adverse Events Reporting System. Dermatology 2023; 239:694-699. [PMID: 37054693 DOI: 10.1159/000530107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 03/06/2023] [Indexed: 04/15/2023] Open
Abstract
BACKGROUND Medications used in the treatment of dermatologic conditions have been associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), melanoma, and Merkel cell carcinoma (MCC). OBJECTIVE The objective of the study was to examine the relationship between systemic dermatologic medications and skin cancer in the FDA Adverse Event Reporting System (FAERS). METHODS Case-control analyses were performed in FAERS from 1968 to 2021 to examine the reporting odds ratios (RORs) for SCC, BCC, melanoma, and MCC. RESULTS The oral immunosuppressants were all associated with increased ROR of SCC, BCC, melanoma, and MCC. Azathioprine had the highest ROR for SCC (34.13, 95% CI 29.07-40.08), BCC (21.15, 95% CI 20.63-25.98), and MCC (44.76, 95% CI 31.52-63.55), while quinacrine and guselkumab had the highest ROR for melanoma (13.14, 95% CI 1.84-93.89 vs. 12.73, 95% CI 10.60-15.30, respectively). The TNF-α inhibitors were associated with an increased ROR for all skin cancers investigated. CONCLUSIONS The oral immunosuppressants and many biologic medications were associated with an increased ROR of skin cancers including TNF-α inhibitors (etanercept, adalimumab, infliximab), IL-23 or IL-12/23 inhibitors (ustekinumab, risankizumab), and the CD-20 inhibitor rituximab but not dupilumab or IL-17 inhibitors.
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24
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Papp KA, Melosky B, Sehdev S, Hotte SJ, Beecker JR, Kirchhof MG, Turchin I, Dutz JP, Gooderham MJ, Gniadecki R, Hong CH, Lambert J, Lynde CW, Prajapati VH, Vender RB. Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours: Inference-Based Guidance from a Multidisciplinary Expert Panel. Dermatol Ther (Heidelb) 2023; 13:867-889. [PMID: 36929121 PMCID: PMC10060504 DOI: 10.1007/s13555-023-00905-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 02/15/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns. OBJECTIVES We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, "In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?" METHODS We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic. RESULTS We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement. CONCLUSIONS Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.
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Affiliation(s)
- Kim A Papp
- Probity Medical Research Inc., Waterloo, ON, Canada.
- Alliance Clinical Research, Waterloo, ON, Canada.
| | - Barbara Melosky
- Medical Oncology, BC Cancer Vancouver Centre, Vancouver, BC, Canada
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Sandeep Sehdev
- Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Sebastien J Hotte
- Juravinski Cancer Centre, Hamilton, ON, Canada
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Jennifer R Beecker
- Probity Medical Research Inc., Waterloo, ON, Canada
- University of Ottawa, Ottawa, ON, Canada
- Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Mark G Kirchhof
- University of Ottawa, Ottawa, ON, Canada
- Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada
| | - Irina Turchin
- Probity Medical Research Inc., Waterloo, ON, Canada
- Brunswick Dermatology Centre, Fredericton, NB, Canada
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Jan P Dutz
- Skin Care Centre, Vancouver, BC, Canada
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
- BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Melinda J Gooderham
- Probity Medical Research Inc., Waterloo, ON, Canada
- SKiN Centre for Dermatology, Peterborough, ON, Canada
| | - Robert Gniadecki
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Chih-Ho Hong
- Probity Medical Research Inc., Waterloo, ON, Canada
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
- Dr. Chih-ho Hong Medical Inc., Surrey, BC, Canada
| | - Jo Lambert
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
- Dermatology Research Unit, Ghent University, Ghent, Belgium
| | - Charles W Lynde
- Probity Medical Research Inc., Waterloo, ON, Canada
- Lynde Institute for Dermatology, Markham, ON, Canada
- Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Vimal H Prajapati
- Probity Medical Research Inc., Waterloo, ON, Canada
- Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
- Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Dermatology Research Institute, Calgary, AB, Canada
- Skin Health & Wellness Centre, Calgary, AB, Canada
| | - Ronald B Vender
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Dermatrials Research Inc., Hamilton, ON, Canada
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Jiang Y, Chen Y, Yu Q, Shi Y. Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities. BioDrugs 2023; 37:35-55. [PMID: 36592323 PMCID: PMC9837020 DOI: 10.1007/s40259-022-00569-z] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2022] [Indexed: 01/03/2023]
Abstract
Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.
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Affiliation(s)
- Yuxiong Jiang
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Youdong Chen
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Qian Yu
- Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
| | - Yuling Shi
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
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26
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Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, Morita A, Szepietowski JC, Imafuku S, Colston E, Throup J, Kundu S, Schoenfeld S, Linaberry M, Banerjee S, Blauvelt A. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol 2023; 88:29-39. [PMID: 35820547 DOI: 10.1016/j.jaad.2022.07.002] [Citation(s) in RCA: 161] [Impact Index Per Article: 80.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 07/01/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Effective, well-tolerated oral psoriasis treatments are needed. OBJECTIVE To compare the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, versus placebo and apremilast in adults with moderate to severe plaque psoriasis. METHODS Participants were randomized 2:1:1 to deucravacitinib 6 mg every day (n = 332), placebo (n = 166), or apremilast 30 mg twice a day (n = 168) in the 52-week, double-blinded, phase 3 POETYK PSO-1 trial (NCT03624127). Coprimary end points included response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) with deucravacitinib versus placebo at week 16. RESULTS At week 16, response rates were significantly higher with deucravacitinib versus placebo or apremilast for PASI 75 (194 [58.4%] vs 21 [12.7%] vs 59 [35.1%]; P < .0001) and sPGA 0/1 (178 [53.6%] vs 12 [7.2%] vs 54 [32.1%]; P < .0001). Efficacy improved beyond week 16 and was maintained through week 52. Adverse event rates with deucravacitinib were similar to those with placebo and apremilast. LIMITATIONS One-year duration, limited racial diversity. CONCLUSION Deucravacitinib was superior to placebo and apremilast across multiple efficacy end points and was well tolerated in moderate to severe plaque psoriasis.
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Affiliation(s)
- April W Armstrong
- Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California.
| | - Melinda Gooderham
- SKiN Centre for Dermatology, Department of Dermatology at Queen's University, and Probity Medical Research, Peterborough, Ontario, Canada
| | - Richard B Warren
- Dermatology Centre at Salford Royal NHS Foundation Trust Hospital, NIHR Manchester Biomedical Research Centre at the University of Manchester, Manchester, United Kingdom
| | - Kim A Papp
- K Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada
| | - Bruce Strober
- Department of Dermatology, Yale University School of Medicine, New Haven, and Central Connecticut Dermatology Research, Cromwell, Connecticut
| | - Diamant Thaçi
- Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany
| | - Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi, Japan
| | - Jacek C Szepietowski
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wrocław, Poland
| | - Shinichi Imafuku
- Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
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27
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Chou YJ, Wu CY, Pan TY, Wu CY, Chang YT. Risk of malignancy in patients with psoriasis receiving systemic medications: a nested case-control study. Dermatol Ther 2022; 35:e15804. [PMID: 36068977 DOI: 10.1111/dth.15804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/24/2022] [Accepted: 09/01/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Large-scale, real-world studies on the side effects of systemic therapies (including biologics) in patients with psoriasis are limited. OBJECTIVE We aimed to calculate the risk of malignancy in patients with psoriasis who were treated with systemic medications. METHODS Nested case-control analyses were performed among psoriasis patients without a history of malignancy. We recruited 4,188 patients with newly diagnosed psoriasis and successive malignancies, and 8,376 matched controls from the National Health Insurance Research Database in Taiwan. The therapy duration was within 5 years before malignancy onset and further stratified into two groups according to the duration of medication usage. Multivariate conditional logistic regression adjusted for potential confounders was used to estimate malignancy risk associated with systemic treatments. RESULTS Among psoriasis patients, long-term (> 12 months) treatment with cyclosporine increased the risk of malignancy compared with no exposure (odds ratio, 1.57; P=0.01). Short-term (≤ 12 months) or long-term (> 12 months) use of other systemic treatments, including methotrexate, azathioprine, systemic retinoids, mycophenolate mofetil, sulfasalazine, etanercept, adalimumab, and ustekinumab, was not associated with an increased risk of malignancy in patients with psoriasis. CONCLUSIONS Long-term treatment with cyclosporine increased the risk of malignancy in patients with psoriasis by 1.57-fold. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Yu-Ju Chou
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Ying Wu
- Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan.,College of Public Health, China Medical University Taichung, Taiwan
| | - Tzu-Yun Pan
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chen-Yi Wu
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Public Health and Department of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Dermatology, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yun-Ting Chang
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Dermatology, National Yang Ming Chiao Tung University, Taipei, Taiwan
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28
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Drug Survival, Safety, and Effectiveness of Biologics in Older Patients with Psoriasis: A Comparison with Younger Patients-A BioCAPTURE Registry Study. Drugs Aging 2022; 39:715-727. [PMID: 35859228 PMCID: PMC9300332 DOI: 10.1007/s40266-022-00961-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.
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29
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Schmalzing M. [Management of inflammatory rheumatic diseases during and after malignancies]. Z Rheumatol 2022; 81:766-777. [PMID: 35796758 DOI: 10.1007/s00393-022-01237-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2022] [Indexed: 11/24/2022]
Abstract
The management of inflammatory rheumatic diseases in patients with a simultaneous or previous malignant disease is associated with complex questions. Difficulties and possible solutions in the interpretation of meaningful studies are presented. Recommendations in guidelines on this topic are discussed. National registries and health insurance databases were examined with respect to the risk of tumor recurrence under disease-modifying antirheumatic drugs; however, these analyses mainly refer to tumor necrosis factor (TNF) inhibitors and rituximab. Data on tumor incidence and, if available, risk of tumor recurrence are summarized for commonly used disease-modifying antirheumatic drugs. Finally, an attempt is made to formulate proposals for rheumatological treatment in patients with a history of malignancy.
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Affiliation(s)
- Marc Schmalzing
- Rheumatologie/Klinische Immunologie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Deutschland.
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30
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Daugaard C, Iversen L, Hjuler KF. Comorbidity in Adult Psoriasis: Considerations for the Clinician. PSORIASIS (AUCKLAND, N.Z.) 2022; 12:139-150. [PMID: 35712227 PMCID: PMC9196664 DOI: 10.2147/ptt.s328572] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/24/2022] [Indexed: 01/19/2023]
Abstract
Psoriasis is associated with several comorbidities ranging from cardiovascular comorbidity and mental disorders to other immune mediated inflammatory diseases. However, most of these co-morbidities are often overlooked or diagnosed late. Furthermore, evidence suggests that comorbidities are undertreated. Here, we provide an overview of comorbidities in psoriasis and present a simple rundown of considerations of relevance to the clinician. We hope that this review may raise clinicians' awareness of comorbidities in psoriasis and provide simple guidance regarding screening tools and treatment decisions in psoriasis with comorbidities.
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Affiliation(s)
- Christine Daugaard
- Department of Dermatology and Venereology, Aarhus University Hospital, Aarhus, Denmark
| | - Lars Iversen
- Department of Dermatology and Venereology, Aarhus University Hospital, Aarhus, Denmark
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Hasan B, Tandon KS, Miret R, Khan S, Riaz A, Gonzalez A, Rahman AU, Charles R, Narula N, Castro FJ. Ustekinumab does not increase risk of new or recurrent cancer in inflammatory bowel disease patients with prior malignancy. J Gastroenterol Hepatol 2022; 37:1016-1021. [PMID: 35191100 DOI: 10.1111/jgh.15806] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/09/2022] [Accepted: 01/23/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIM There is limited data on the rate of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a history of prior or current malignancy who are initiated on biologic therapies. Furthermore, there is no data on this topic in patients using ustekinumab. METHODS The retrospective study included 341 patients with IBD and a history of cancer who were subsequently treated with vedolizumab (VDZ; n = 34), ustekinumab (USK; n = 27), tumor necrosis factor α antagonists (anti-TNF; n = 99), or had no immunosuppressive therapy (control; n = 181). Cox proportional hazard models were developed to determine the independent effect of post-cancer immunosuppressive treatment on the occurrence of incident cancer. RESULTS Over a median of 5.2 person-years of follow up, cancer recurrence occurred in only one patient on anti-TNF, while new cancers developed in one patient on VDZ, three patients on USK, and six patients on anti-TNF, corresponding to cancer rates of 0.4, 1.8, and 0.7 per 100 person-years, respectively. The rate of incident cancer in control patients was 2.4 per 100 person-years and included 18 new and 9 recurrent cancers. Compared with controls, a stepwise Cox proportional hazards model adjusting for significant covariates found no increased risk of incident cancer in patients receiving post-malignancy treatment with USK (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.25-3.03), VDZ (HR 0.18; 95% CI 0.03-1.35), or anti-TNF (HR 0.47; 95% CI 0.20-1.12). CONCLUSION Use of biologic therapy in IBD patients with a previous history of malignancy was not associated with an increased risk of new or recurrent cancer.
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Affiliation(s)
- Badar Hasan
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida, USA
| | | | - Rafael Miret
- Department of Internal Medicine, Cleveland Clinic Florida, Weston, Florida, USA
| | - Sikandar Khan
- Department of Internal Medicine, Cleveland Clinic Florida, Weston, Florida, USA
| | - Amir Riaz
- Department of Internal Medicine, Cleveland Clinic Florida, Weston, Florida, USA
| | - Adalberto Gonzalez
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida, USA
| | - Asad Ur Rahman
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida, USA
| | - Roger Charles
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida, USA
| | - Neeraj Narula
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Fernando J Castro
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida, USA
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Hong JJ, Hadeler EK, Mosca ML, Brownstone ND, Bhutani T, Liao WJ. TNF-alpha inhibitors and ustekinumab for the treatment of psoriasis: therapeutic utility in the era of IL-17 and IL-23 inhibitors. JOURNAL OF PSORIASIS AND PSORIATIC ARTHRITIS 2022; 7:79-92. [PMID: 35757187 PMCID: PMC9229820 DOI: 10.1177/24755303211047479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.
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Affiliation(s)
- Julie J Hong
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Edward K Hadeler
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Megan L Mosca
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Nicholas D Brownstone
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Tina Bhutani
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Wilson J Liao
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
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Lenti MV, Dolby V, Clark T, Hall V, Tattersall S, Fairhurst F, Kenneth C, Walker R, Kemp K, Borg‐Bartolo S, Limdi JK, Taylor J, Townsend T, Subramanian S, Storey D, Assadsangabi A, Stansfield C, Smith P, Byrne D, De Silvestri A, Selinger C. A propensity score-matched, real-world comparison of ustekinumab vs vedolizumab as a second-line treatment for Crohn's disease. The Cross Pennine study II. Aliment Pharmacol Ther 2022; 55:856-866. [PMID: 34935160 PMCID: PMC9305775 DOI: 10.1111/apt.16742] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/06/2021] [Accepted: 12/09/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND The optimal choice of biological agents after failure of anti-tumour-necrosis-factor-(TNF)α agent in Crohn's disease (CD) is yet to be defined. AIMS To assess the effectiveness and safety of ustekinumab compared to vedolizumab as second-line treatment in CD patients who failed anti-TNFα therapy. METHODS Retrospective analysis of clinical response and remission at 14 and 52 weeks to ustekinumab by physician global assessment (PGA). A propensity score-matched analysis with a cohort treated with vedolizumab was performed. RESULTS Of 282 patients (mean age 40 ± 15, F:M ratio 1.7:1) treated with ustekinumab, clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and 162/259 patients (62.5%) at 52 weeks. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person-year). After exclusion of patients without prior anti-TNFα exposure and patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) on ustekinumab and 118/135 patients (87.4%) on vedolizumab. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25%-50%; P < 0.001) more likely to achieve clinical remission, while at 52 weeks, the difference of 9% (95% CI -15% to 33%; P = 0.462) was not significant. CONCLUSIONS Ustekinumab was effective and well tolerated in this real-world cohort. While ustekinumab proved more effective at 14-weeks, we found no statistically significant differences at 52 weeks compared to vedolizumab.
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Gasslitter I, Löffler-Ragg J, Schmidt E, Schmuth M, Gruber R. Coincidence of Bullous Pemphigoid and Pityriasis Rubra Pilaris. Acta Derm Venereol 2022; 102:adv00674. [PMID: 35170740 PMCID: PMC9558747 DOI: 10.2340/actadv.v102.1289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Irina Gasslitter
- Dermatology, venereology and allergy, Medical University of Innsbruck, Innsbruck, Austria.
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Patel S, Kumthekar A. Psoriatic Arthritis: The Influence of Co-morbidities on Drug Choice. Rheumatol Ther 2022; 9:49-71. [PMID: 34797530 PMCID: PMC8814223 DOI: 10.1007/s40744-021-00397-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/28/2021] [Indexed: 12/20/2022] Open
Abstract
Psoriatic arthritis (PsA) is associated with a higher burden of co-morbidities such as obesity, cardiovascular disease, non-alcoholic fatty liver disease, inflammatory eye disease, inflammatory bowel disease, skin cancer and depression compared to the general population. In the last 20 years, the therapeutic options for PsA have increased exponentially with the availability of tumor necrosis factor-alpha (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-12/23 inhibitors and Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) inhibitors. The articular and extra-articular manifestations of PsA usually dictate the treatment choice but important consideration must be given to the corresponding co-morbidities while deciding the drug therapy due to associated safety profile, effect on disease activity, etc. This review provides a comprehensive review of common co-morbidities in PsA and how they can influence treatment choices.
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Affiliation(s)
- Sneha Patel
- Rheumatology, Acclaim Physicians/JPS Hospital, Fort Worth, TX, USA
| | - Anand Kumthekar
- Division of Rheumatology, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, USA.
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Treatment Options and Goals for Patients with Generalized Pustular Psoriasis. Am J Clin Dermatol 2022; 23:51-64. [PMID: 35061230 PMCID: PMC8801408 DOI: 10.1007/s40257-021-00658-9] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2021] [Indexed: 12/17/2022]
Abstract
Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disorder characterized by sudden widespread eruption of superficial sterile pustules with or without systemic inflammation. GPP flares can be life-threatening if untreated due to potential severe complications such as cardiovascular failure and serious infections. Currently, there are no GPP-specific therapies approved in the USA or Europe. Retinoids, cyclosporine, and methotrexate are the most commonly used non-biologic therapies for GPP. The evidence that supports the currently available treatment options is mainly based on case reports and small, open-label, single-arm studies. However, recent advances in our understanding of the pathogenic mechanisms of GPP and the identification of gene mutations linked to the disease have paved the way for the development of specific targeted therapies that selectively suppress the autoinflammatory and autoimmune mechanisms induced during GPP flares. Several biologic agents that target key cytokines involved in the activation of inflammatory pathways, such as tumor necrosis factor-α blockers and interleukin (IL)-17, IL-23, and IL-12 inhibitors, have emerged as potential treatments for GPP, with several being approved in Japan. The evidence supporting the efficacy of these agents is mainly derived from small, uncontrolled trials. A notable recent advance is the discovery of IL36RN mutations and the central role of IL-36 receptor ligands in the pathogenesis of GPP, which has defined key therapeutic targets for the disease. Biologic agents that target the IL-36 pathway have demonstrated promising efficacy in patients with GPP, marking the beginning of a new era of targeted therapy for GPP.
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Singh R, Koppu S, Perche PO, Feldman SR. The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications. Int J Mol Sci 2021; 22:12793. [PMID: 34884596 PMCID: PMC8657643 DOI: 10.3390/ijms222312793] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/19/2021] [Accepted: 11/25/2021] [Indexed: 12/27/2022] Open
Abstract
Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis', the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis', an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.
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Affiliation(s)
- Rohan Singh
- Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; (R.S.); (S.K.); (P.O.P.)
| | - Sindhuja Koppu
- Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; (R.S.); (S.K.); (P.O.P.)
| | - Patrick O. Perche
- Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; (R.S.); (S.K.); (P.O.P.)
| | - Steven R. Feldman
- Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; (R.S.); (S.K.); (P.O.P.)
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
- Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
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Diakomopoulos A, Dalamaga M, Papadavid E. Understanding the enigmatic association between mycosis fungoides and psoriasis: Report of two cases and review of the literature. Metabol Open 2021; 12:100148. [PMID: 34816115 PMCID: PMC8591362 DOI: 10.1016/j.metop.2021.100148] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 11/02/2021] [Indexed: 01/04/2023] Open
Abstract
Psoriatic patients present an increased risk for developing lymphoma, particularly cutaneous T-cell lymphoma (CTCL). To what degree psoriasis itself through chronic immune stimulation, or the immunosuppressive medications used for its treatment or comorbidities (obesity, diabetes mellitus, etc), or lifestyle (smoking, alcohol, diet, etc) may play a role in the onset of MF is not yet clear. Psoriasis and Mycosis Fungoides (MF), the most common variant of CTCL, represent two distinct entities sharing common pathogenetic mechanisms and a wide spectrum of common clinical features associated with the abnormal activation of T-cells. The aim of this study is to explore the relationship between MF and psoriasis by presenting two cases with clinical and histopathologic features of both psoriasis and MF with a particular emphasis on the time of presentation of both disorders, the use of previous immunosuppressive drugs as well as the therapeutic management of patients. Biopsy of the cutaneous lesions before the introduction of biologics should be incorporated in clinical practice. Biopsy of the cutaneous lesion should also be performed in the case of appearance of psoriasiform lesions during biologic treatment for autoimmune disorders because this may represent an indolent form of MF. Psoriatic patients with poor or no-response to treatment should be examined thoroughly for MF using immunochemistry and, if necessary, molecular biology techniques. In concomitant MF and psoriasis, combination treatment may be beneficial for both entities. Finally, a large multicentric registry of MF patients who were treated for benign dermatoses (i.e. eczema, psoriasis) with classic immunosuppressive drugs and/or biologics is needed to collect data and further clarify the enigmatic relationship between psoriasis, MF and immunosuppressive treatment.
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Affiliation(s)
- Achilleas Diakomopoulos
- 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, 1 Rimini Street, 12462, Athens, Chaidari, Greece
| | - Maria Dalamaga
- 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, 1 Rimini Street, 12462, Athens, Chaidari, Greece.,Department of Biological Chemistry, Medical School, National & Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece
| | - Evangelia Papadavid
- 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, 1 Rimini Street, 12462, Athens, Chaidari, Greece
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Marwaha AK, Chow S, Pesenacker AM, Cook L, Sun A, Long SA, Yang JHM, Ward-Hartstonge KA, Williams E, Domingo-Vila C, Halani K, Harris KM, Tree TIM, Levings MK, Elliott T, Tan R, Dutz JP. A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes. IMMUNOTHERAPY ADVANCES 2021; 2:ltab022. [PMID: 35072168 PMCID: PMC8769169 DOI: 10.1093/immadv/ltab022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 09/22/2021] [Accepted: 11/11/2021] [Indexed: 12/25/2022] Open
Abstract
Objectives We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia. Methods We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: (i) 45 mg loading weeks 0/4/16, (ii) 45 mg maintenance weeks 0/4/16/28/40, (iii) 90 mg loading weeks 0/4/16, and (iv) 90 mg maintenance weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses. Results Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90 mg maintenance dosing cohort had the smallest mean decline in C-peptide area under the curve (AUC) (0.1 pmol/ml). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1, and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A. Conclusion Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90 mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response.
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Affiliation(s)
- Ashish K Marwaha
- Department of Medical Genetics, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
| | - Samuel Chow
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Anne M Pesenacker
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | - Laura Cook
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Annika Sun
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
| | - S Alice Long
- Benaroya Research Institute at Virginia Mason, Translational Research Program, Seattle, WA, USA
| | - Jennie H M Yang
- Department of Immunobiology, King’s College London, London, UK
| | - Kirsten A Ward-Hartstonge
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | | | | | | | | | | | - Megan K Levings
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | - Thomas Elliott
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- BCDiabetes, Vancouver, British Columbia, Canada
| | - Rusung Tan
- Department of Pathology, Sidra Medicine and Weill Cornell Medicine, Doha, Qatar
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jan P Dutz
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
- BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
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40
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Fumery M, Filippi J, Abitbol V, Biron A, Laharie D, Serrero M, Altwegg R, Bouhnik Y, Peyrin-Biroulet L, Gilletta C, Roblin X, Pineton de Chambrun G, Vuitton L, Bourrier A, Nancey S, Gornet JM, Nahon S, Bouguen G, Viennot S, Nachury M, Amiot A. Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study. Aliment Pharmacol Ther 2021; 54:944-951. [PMID: 34296456 DOI: 10.1111/apt.16544] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/10/2021] [Accepted: 07/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. AIMS To assess the real-world effectiveness and safety of ustekinumab in patients with UC. METHODS From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. RESULTS We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti-TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid-free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3-10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. CONCLUSION After 52 weeks, over one-half of patients with refractory UC were still treated by ustekinumab and one-third were in steroid-free clinical remission.
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Greuter T, Vavricka S, König AO, Beaugerie L, Scharl M. Malignancies in Inflammatory Bowel Disease. Digestion 2021; 101 Suppl 1:136-145. [PMID: 32799195 DOI: 10.1159/000509544] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 05/11/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to, the gut. Association between IBD and cancer has been clearly established and is uniformly accepted. SUMMARY IBD patients are at particular risk for intestinal and extraintestinal cancers. There are 2 underlying mechanisms: (1) IBD-related inflammation triggers initiation and progression of tumor formation. This particularly results in the development of colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, anal cancer, and cholangiocarcinoma. (2) Immunosuppressive drugs exhibit carcinogenic properties such as shown for azathioprine and anti-TNF promoting lymphoproliferative malignancies and melanoma and nonmelanoma skin cancer. However, within the last years, IBD-related cancer incidence and prevalence have been decreasing, which might be attributed to better treatment options and surveillance strategies. Moreover, novel biological drugs have been introduced in clinical practice and have dramatically changed long-term IBD management. Therefore, we sought to summarize up-to-date knowledge about (1) overall cancer risk; (2) risk and protective factors for cancer development; and (3) inflammation- and immunosuppression-related malignancies in the current anti-TNF era of IBD. Key Messages: Recent studies and meta-analyses questioned the excess rates of cancer in IBD patients. However, IBD still is associated with cancer development due to ongoing intestinal inflammation and the use of potential carcinogenic drugs. Patients should be educated about the increased risk of cancer with IBD and IBD drugs. However, they should also be informed that most malignancy subtypes are possibly preventable by controlling intestinal inflammation and by using adequate screening strategies.
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Affiliation(s)
- Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, .,Department of Internal Medicine, GZO - Zurich Regional Health Center, Wetzikon, Switzerland,
| | - Stephan Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.,Center for Gastroenterology and Hepatology, Zurich, Switzerland
| | - Alexander O König
- Department of Gastroenterology and Hepatology, University of Göttingen, Göttingen, Germany
| | - Laurent Beaugerie
- Department of Gastroenterology, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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van de Kerkhof PCM. The risk of malignancy in patients with secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis. Br J Dermatol 2021; 185:879. [PMID: 34402525 DOI: 10.1111/bjd.20624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/03/2021] [Accepted: 06/06/2021] [Indexed: 11/26/2022]
Affiliation(s)
- P C M van de Kerkhof
- Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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Semaka A, Salopek TG. Risk of Developing Melanoma With Systemic Agents Used to Treat Psoriasis: A Review of the Literature. J Cutan Med Surg 2021; 26:87-92. [PMID: 34392725 PMCID: PMC8750137 DOI: 10.1177/12034754211038509] [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] [Indexed: 11/16/2022]
Abstract
Background Psoriasis is a chronic inflammatory skin disease induced by
autoimmune-like dysregulation of the immune system. Treatment
options have drastically evolved in recent years, and treatment
advances that target specific cytokines and other molecules
involved in dysregulation have had a profound effect in
controlling the disease. Objective We reviewed the literature to assess the risk of developing
melanoma with conventional therapies and newer agents used to
treat psoriasis. Methods A comprehensive literature search using Medline (via Ovid) and
Embase was conducted. Results The majority of studies reviewed reported insignificant results.
Potential risk for melanoma was identified for only 3 out of 15
anti-psoriatic treatments analyzed: adalimumab (relative risk
1.8, 95% CI 1.06-3.00), etanercept (relative risk 2.35, 95% CI
1.46-3.77) and infliximab (Empirical Bayes Geometric Mean 7.90,
95% CI 7.13-8.60). The confidence intervals provided are from
prior studies. There are not enough collective data on newer
agents to make any conclusions on risk. Conclusions We were unable to identify any substantial risk for developing
melanoma due to the use of anti-psoriatic treatments. Until
additional long-term registry data become available, it would be
prudent to continue screening patients with psoriasis at
baseline and periodically for melanoma when these agents are
used.
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Affiliation(s)
- Amy Semaka
- 3158 Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Thomas G Salopek
- Division of Dermatology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
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Bellinato F, Gisondi P, Girolomoni G. Risk of lymphohematologic malignancies in patients with chronic plaque psoriasis: A systematic review with meta-analysis. J Am Acad Dermatol 2021; 86:86-96. [PMID: 34363908 DOI: 10.1016/j.jaad.2021.07.050] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 07/01/2021] [Accepted: 07/22/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND The association between chronic plaque psoriasis and lymphohematologic malignancies (LHMs) remains controversial. OBJECTIVE To investigate the risk of LHMs in patients with psoriasis according to the best evidence. METHODS A systematic review and meta-analysis of observational cohort studies was undertaken to assess the association of psoriasis with different LHMs. A literature search for relevant studies was performed on February 28, 2021. The random-effects model in conducting meta-analyses was applied. To evaluate the risk of bias, the Newcastle-Ottawa Scale was employed. RESULTS A total of 25 observational studies were selected, comprising collectively 2,501,652 subjects. A significantly increased risk for LHM (hazard ratio [HR], 1.55; 1.24-2.94) and lymphoma (HR, 1.27; 1.08-1.50) in patients with moderate-to-severe plaque psoriasis compared to the general population was found. In detail, increased risks for Hodgkin lymphoma (HR, 1.71; 1.27-2.30), non-Hodgkin lymphoma (HR, 1.27; 1.08-1.50), multiple myeloma (HR, 1.32; 1.03-1.69), and leukemia (HR, 1.28; 1.00-1.65) were found. The risk of cutaneous T-cell lymphoma was markedly augmented in patients with psoriasis (HR, 6.22; 3.39-11.42). LIMITATIONS Possible ascertainment bias related to the diagnosis of LHMs. CONCLUSION The increased risk of LHMs, particularly cutaneous T-cell lymphoma, in patients with psoriasis could be related to exposure to systemic immunosuppressive therapies, comorbidities, and sustained immune activation, particularly in the skin.
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Affiliation(s)
- Francesco Bellinato
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy.
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - Giampiero Girolomoni
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
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45
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Cohen-Sors R, Fougerousse AC, Reguiai Z, Maccari F, Mahé E, Delaunay J, Roussel A, de la Breteque MA, Cottencin C, Bertolotti A, Kemp H, Chaby G. Biological Therapies or Apremilast in the Treatment of Psoriasis in Patients with a History of Hematologic Malignancy: Results from a Retrospective Study in 21 Patients. Clin Cosmet Investig Dermatol 2021; 14:845-854. [PMID: 34267533 PMCID: PMC8275167 DOI: 10.2147/ccid.s320098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 06/25/2021] [Indexed: 01/30/2023]
Abstract
Background Few studies addressing the safety and efficacy of biological therapy (BT) or apremilast (APR) in patients with psoriasis with a history of hematologic malignancy (HM) exist. Aim To describe the tolerance and efficacy of BT and APR in moderate-to-severe psoriasis in patients with a history of in-remission or evolving HM. Methodology A retrospective, multicenter chart review of the tolerance and efficacy of BT or APR in patients with moderate-to-severe psoriasis and a clinical history of in-remission or evolving HM. Results Twenty-one patients with severe psoriasis and a history of HM were included in France by the GEM Resopso study group. Of the 16 patients treated with one or more BT lines, none showed recurrence of their HM which was considered as stable or in remission, and only 2 patients showed an evolution of their HM which had been considered as stable at the beginning of treatment. In the 10 patients treated with APR, the HM of one patient who also received BT worsened. The 3 evolutions did not impact the treatment with BT or APR. Tolerance was very satisfactory, with a low occurrence of infections. Regarding efficacy, only one patient treated with APR did not achieve any notable clinical improvement. Conclusion Despite supportive data regarding tolerance, the heterogeneity of the analyzed population and limited available data, BT and APR should be used with caution in this patient population and investigations on larger cohorts should be conducted to further assess their tolerance in this patient population.
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Affiliation(s)
- Raphaella Cohen-Sors
- Dermatology Department, Amiens-Picardie University Hospital Center, Amiens, France
| | | | - Ziad Reguiai
- Dermatology Department, Polyclinic Courlancy, Reims, France
| | - Francois Maccari
- Dermatology Department, Military Teaching Hospital Bégin, Saint-Mandé, France
| | - Emmanuel Mahé
- Dermatology Department, Argenteuil Hospital, Argenteuil, France
| | | | - Aude Roussel
- Dermatology Department, Military Teaching Hospital Bégin, Saint-Mandé, France
| | | | | | - Antoine Bertolotti
- Dermatology Department, University Hospital, Saint-Pierre, Ile de la Réunion, France
| | - Hélène Kemp
- Hematology Department, Amiens-Picardie University Hospital Center, Amiens, France
| | - Guillaume Chaby
- Dermatology Department, Amiens-Picardie University Hospital Center, Amiens, France
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46
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Sandborn WJ, Feagan BG, Danese S, O’Brien CD, Ott E, Marano C, Baker T, Zhou Y, Volger S, Tikhonov I, Gasink C, Sands BE, Ghosh S. Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies. Inflamm Bowel Dis 2021; 27:994-1007. [PMID: 32964215 PMCID: PMC8205635 DOI: 10.1093/ibd/izaa236] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Ustekinumab is currently approved globally in Crohn's disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn's disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses. METHODS Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed. RESULTS Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81-176.67] vs ustekinumab 118.32 [95% CI, 113.25-123.55]), serious AEs (27.50 [95% CI, 23.45-32.04] vs 21.23 [95% CI, 19.12-23.51]), infections (80.31 [95% CI, 73.28-87.84] vs 64.32 [95% CI, 60.60-68.21]), serious infections (5.53 [95% CI, 3.81-7.77] vs 5.02 [95% CI, 4.02-6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00-0.93] vs 0.40 [95% CI, 0.16-0.83]) were similar between placebo and ustekinumab. CONCLUSIONS The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications. CLINICALTRIALS.GOV NUMBERS NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.
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Affiliation(s)
| | - Brian G Feagan
- Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada
| | - Silvio Danese
- Humanitas Clinical Research Center-IRCCS and Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | | | - Elyssa Ott
- Janssen Scientific Affairs, LLC, Horsham, PA, USA
| | - Colleen Marano
- Janssen Research & Development, LLC, Spring House, PA, USA
| | - Thomas Baker
- Janssen Scientific Affairs, LLC, Horsham, PA, USA
| | - Yiying Zhou
- Janssen Research & Development, LLC, Spring House, PA, USA
| | - Sheri Volger
- Janssen Research & Development, LLC, Spring House, PA, USA
| | - Ilia Tikhonov
- Janssen Research & Development, LLC, Spring House, PA, USA
| | | | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Subrata Ghosh
- Institute of Translational Medicine and NIHR Biomedical Research Center, University of Birmingham, United Kingdom
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Crisafulli S, Bertino L, Fontana A, Calapai F, Ingrasciotta Y, Berretta M, Trifirò G, Guarneri C. Incidence of Skin Cancer in Patients With Chronic Inflammatory Cutaneous Diseases on Targeted Therapies: A Systematic Review and Meta-Analysis of Observational Studies. Front Oncol 2021; 11:687432. [PMID: 34150655 PMCID: PMC8209509 DOI: 10.3389/fonc.2021.687432] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/12/2021] [Indexed: 12/25/2022] Open
Abstract
Cancer is one of the several comorbidities that have been linked with chronic cutaneous inflammatory diseases namely psoriasis/psoriatic arthritis and hidradenitis suppurativa. Although the chronic inflammatory state, typical of the diseases, may induce pro-tumorigenic effects, the debate whether or not the drugs currently used in clinical practice do in facts increase a patient's risk of malignancy remains largely unsolved. The therapeutic armamentarium has been greatly enhanced at least in the last two decades with the advent of biologics, a heterogeneous group of laboratory-engineered agents with more in the pipeline, and other targeted small molecules. Among the organ systems, skin results as one of the most commonly affected, non-melanoma skin cancers being the main drug-induced manifestations as side effect in course of these treatments. The objective of the study is to systematically review the cutaneous malignancy risk of the newer therapies through an overview of meta-analyses and observational studies on the topic.
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Affiliation(s)
- Salvatore Crisafulli
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Lucrezia Bertino
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Andrea Fontana
- Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Fabrizio Calapai
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Ylenia Ingrasciotta
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, Section of Infectious Diseases, University of Messina, Messina, Italy
| | - Gianluca Trifirò
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Claudio Guarneri
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
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Bissonnette R, Gottlieb AB, Langley RG, Leonardi CL, Papp KA, Pariser DM, Uy J, Lafferty KP, Langholff W, Fakharzadeh S, Berlin JA, Brouwer ES, Greenspan AJ, Strober BE. Signal Detection and Methodological Limitations in a Real-World Registry: Learnings from the Evaluation of Long-Term Safety Analyses in PSOLAR. Drug Saf 2021; 44:699-709. [PMID: 34075572 PMCID: PMC8184557 DOI: 10.1007/s40264-021-01065-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2021] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Psoriasis Longitudinal Assessment and Registry (PSOLAR) was designed in 2007 as the first disease-based registry for patients with psoriasis. OBJECTIVE The aim of this study was to discuss methodological limitations and post hoc analyses in long-term safety registries using learnings from analyses of a potential safety risk for major adverse cardiovascular events (MACE) in PSOLAR. METHODS PSOLAR is an international observational study of over 12,000 psoriasis patients that was conducted to meet postmarketing safety commitments for infliximab and ustekinumab. A recent annual review of registry data indicated a potential MACE risk for ustekinumab vs. non-biologics based on prespecified COX model regression analyses, which yielded an adjusted hazard ratio (HR) of 1.533 (95% confidence interval [CI] 1.103-2.131). Therefore, we conducted a comprehensive review of key statistical methodology and implemented post hoc analytical methods to address specific limitations. RESULTS The following limiting factors were identified: (1) inclusion of both prevalent and incident (new) users of biologics; (2) unanticipated imbalances in patient characteristics between treatment cohorts at baseline; (3) limited availability of relevant clinical data after enrollment; and (4) divergence of characteristics associated with outcomes among comparator groups over time. The analysis was modified to include only incident users, propensity scores were used to weight HRs, and adalimumab was deemed a more clinically appropriate comparator. The revised HR was 0.820 (95% CI 0.532-1.265), indicating no meaningful increase in MACE risk for ustekinumab. CONCLUSION Our results, which do not support a causal association between ustekinumab exposure and MACE risk, underscore the need for ongoing assessment of analytical methods in long-term observational studies.
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Affiliation(s)
- Robert Bissonnette
- Innovaderm Research, Inc., 3530 St-Laurent Blvd, Suite 300, Montreal, QC, H2X 2V1, Canada.
| | | | | | | | - Kim A Papp
- K. Papp Clinical Research and Probity Research Inc., Waterloo, ON, Canada
| | | | - Jonathan Uy
- Janssen Scientific Affairs, LLC, Horsham, PA, USA
| | | | | | | | | | | | | | - Bruce E Strober
- Yale University, New Haven, CT, USA
- Central Connecticut Dermatology Research, Cromwell, CT, USA
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49
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Thaci D, Piaserico S, Warren RB, Gupta AK, Cantrell W, Draelos Z, Foley P, Igarashi A, Langley RG, Asahina A, Young M, Falqués M, Pau-Charles I, Mendelsohn AM, Rozzo SJ, Reich K. Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2). Br J Dermatol 2021; 185:323-334. [PMID: 33544883 DOI: 10.1111/bjd.19866] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/04/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti-interleukin-23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are complete. OBJECTIVES We present 5-year pooled data from reSURFACE 1 and reSURFACE 2. METHODS reSURFACE 1 and reSURFACE 2 were double-blind, randomized, controlled studies with optional long-term extensions. Adults with moderate-to-severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter [reSURFACE 2 included an etanercept (ETN) arm]. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated. RESULTS Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure-adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient-years of TIL 100 and TIL 200, respectively. CONCLUSIONS TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.
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Affiliation(s)
- D Thaci
- Institute and Comprehensive Centre for Inflammation Medicine, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany
| | - S Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Via Vincenzo Gallucci 4, Padua, 35128, Italy
| | - R B Warren
- The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, M6 8HD, UK
| | - A K Gupta
- Division of Dermatology, Department of Medicine, University of Toronto School of Medicine, 190 Elizabeth Street, R. Fraser Elliott Building, 3-805, Toronto, ON, M5G 2C4, Canada.,Mediprobe Research Inc, 645 Windermere Road, London, ON, N5X 2P1, Canada
| | - W Cantrell
- Village Dermatology, 2900 Cahaba Road, Birmingham, AL, 35223, USA
| | - Z Draelos
- Dermatology Consulting Services, 2444 North Main Street, High Point, NC, 27262, USA
| | - P Foley
- Skin Health Institute Inc., Level 1, 80 Drummond Street, Carlton, Victoria, 3053, Australia
| | - A Igarashi
- NTT Medical Center Tokyo, 5-9-22 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - R G Langley
- Division of Dermatology, Department of Medicine, Dalhousie University, 6054 Coburg Road, Halifax, NS, B3H 1Z2, Canada
| | - A Asahina
- Department of Dermatology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - M Young
- Mindful Dermatology, Modern Research Associates, 9101 N Central Expy Ste 160, Dallas, TX, 75231, USA
| | - M Falqués
- Almirall R&D, Carrer de Laureà Miró, 408, 410, Sant Feliu de Llobregat, Barcelona, 08980, Spain
| | - I Pau-Charles
- Almirall R&D, Carrer de Laureà Miró, 408, 410, Sant Feliu de Llobregat, Barcelona, 08980, Spain
| | - A M Mendelsohn
- Sun Pharmaceutical Industries, Inc., 2 Independence Way, Princeton, NJ, 08540, USA
| | - S J Rozzo
- Sun Pharmaceutical Industries, Inc., 2 Independence Way, Princeton, NJ, 08540, USA
| | - K Reich
- Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, M, Hamburg, 20246, Germany
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50
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Management of particular clinical situations in psoriatic arthritis: an expert's recommendation document based on systematic literature review and extended Delphi process. Rheumatol Int 2021; 41:1549-1565. [PMID: 33934175 PMCID: PMC8316175 DOI: 10.1007/s00296-021-04877-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 04/23/2021] [Indexed: 02/07/2023]
Abstract
To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA.
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