1. Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over 2 years in randomized phase 3/3b trials.
- Author
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Lebwohl M, Merola JF, Strober B, Armstrong A, Yoshizaki A, Gisondi P, Szilagyi B, Peterson L, de Cuyper D, Cross N, Davies O, and Gottlieb AB
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Liver Cirrhosis epidemiology, Dermatologic Agents adverse effects, Dermatologic Agents therapeutic use, Incidence, Psoriasis drug therapy, Antibodies, Monoclonal, Humanized adverse effects, Aspartate Aminotransferases blood, Alanine Transaminase blood, Severity of Illness Index, Chemical and Drug Induced Liver Injury epidemiology, Chemical and Drug Induced Liver Injury etiology
- Abstract
Background: Patients with psoriasis are at increased risk of liver function abnormalities., Objective: Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis., Methods: Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY)., Results: 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline., Limitations: Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction., Conclusion: Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods., Competing Interests: Conflicts of interest ML: Employee of Mount Sinai and receives research funds from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly and Company, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Pfizer, Sanofi-Regeneron, and UCB Pharma; consultant for Almirall, AltruBio Inc., AnaptysBio, Apogee, Arcutis Inc., AstraZeneca, Atomwise, Avotres Therapeutics, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, EPI, Evommune Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Genentech, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi, and Verrica. JFM: Consultant and/or investigator for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. BS: Consultant (honoraria) for AbbVie, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Connect Biopharma, CorEvitas, Dermavant, Eli Lilly and Company, Evelo Biosciences, Immunic Therapeutics, Janssen, Kangpu Pharmaceuticals, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Monte Carlo, Novartis, Pfizer, Protangonist, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda/Nimbus, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics; stock options from Connect Biopharma, Mindera Health; speaker for AbbVie, Arcutis, Dermavant, Eli Lilly and Company, Incyte, Janssen, Regeneron, and Sanofi Genzyme; Scientific Co-Director (consulting fee) for CorEvitas Psoriasis Registry; Investigator for CorEvitas Psoriasis Registry; Editor-in-Chief (honorarium) for Journal of Psoriasis and Psoriatic Arthritis. AA: Research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, EPI, Incyte, Janssen, LEO Pharma, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. AY: No conflicts of interest to disclose; PG: Consultant for AbbVie, Abiogen, Almirall, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi, and UCB Pharma; BS, LP, DdC, NC, OD: Employees and shareholders of UCB Pharma. ABG: Honoraria as an advisory board member and consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, DiCE Therapeutics, Eli Lilly and Company, Janssen, Novartis, Sanofi, UCB Pharma, and XBiotech; research/educational grants from AnaptysBio, Bristol Myers Squibb, Highlights Therapeutics, Janssen, MoonLake Therapeutics, Novartis, and UCB Pharma; all funds go to Mount Sinai Medical School., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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