Long-term safety of ixekizumab in adult patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis

Abstract Background/Aims Ixekizumab (IXE) is a high-affinity, monoclonal antibody targeting IL-17A and is approved for the treatment of psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. We report long-term, end-of-study-program, safety outcomes in adult patients with PsO, PsA and axSpA who received at least one dose of IXE over 5 years (PsO) or 3 years (PsA and axSpA). Methods An integrated safety analysis consisting of data from 25 randomised clinical trials (RCTs; 17 PsO, 4 PsA, 4 axSpA) was used to examine long-term safety of IXE. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for all pooled studies by years of therapy and overall through March 2022, and reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at successive year intervals. Additional safety outcomes included selected safety topics of interest (among others). Results A total of 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, with a cumulative IXE exposure of 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA were included in this analysis. The IRs per 100 PY for any TEAE were as follows: patients with PsO=32.5; PsA=50.3; axSpA=38.0. The most commonly reported TEAEs were nasopharyngitis (PsO, IR = 8.8; PsA, IR = 9.0; axSpA IR = 8.4) and upper respiratory tract infection (PsO, IR = 6.2; PsA, IR = 8.3; axSpA IR = 5.8). Serious AEs were reported by 969 patients with PsO (IR = 5.4), 134 patients with PsA (IR = 6), and 101 patients with axSpA (IR = 4.8). Forty-five deaths were reported (PsO=36 [IR = 0.2]; PsA=6 [IR = 0.3]; axSpA=3 [IR = 0.1]). The IRs per 100 PY of discontinuation from the study drug due to AE were as follows: PsO, 2.9; PsA, 5.1; axSpA, 3.1. IRs of injection site reactions were: PsO, 5.9; PsA, 11.6; axSpA, 7.4. IRs of allergic reactions were: PsO, 5.6; PsA, 4.5; axSpA, 4.2. IRs of serious infections were low (PsO, IR = 1.3; PsA, IR = 1.2; axSpA, IR = 1.1). IRs of Candida were low across all indications (PsO, 1.9; PsA, 2.0; axSpA, 1.2), as were IRs of opportunistic infections (PsO, 1.8; PsA, 1.8; axSpA, 1.3). IRs were also low across all indications for depression, major adverse cerebro-cardiovascular events and malignancies (all IRs ≤1.6). Cases of inflammatory bowel disease (IBD) were uncommon (IRs ≤0.8 across indications). Conclusion In this updated analysis with 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA, IXE maintained a long-term safety profile up to 5 years, consistent with previous reports. Disclosure A. Deodhar: Grants/research support; A.D. received direct payments from Eli Lilly and Company as a scientific consultant/speaker, and payments (investigator) made to Oregon Medical Research Center. A. Blauvelt: Consultancies; A.B. received consulting fee from AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor. Member of speakers’ bureau; A.B. discloses direct payment for speaker bureaus from AbbVie, UCB. S. Schwartzman: Consultancies; S.S. is a consultant with AbbVie, Janssen, Lilly, Myriad, Novartis, Regeneron, Sanofi, UCB, Stelexis, Jubilant, and Teijin. Grants/research support; S.S. reports grants/contracts from Eli Lilly and Company, is a board member on the National Psoriasis Foundation Medical Board and part of the Scientific Advisory Board at Myriad. C. Salvarani: None. M. Feely: Shareholder/stock ownership; M.F. is an employee and shareholder at Eli Lilly and Company. Other; M.F. participated on a Data Safety Monitoring or Advisory Board at Eli Lilly and Company, is a Clinical Instructor in Dermatology at Mount Sinai and discloses previous employment with MC Medical Group, reimbursement of fees from Eli Lilly and Company and from Advisory Boards at the DREAM USA South Beach Symposium, is a current member of the AAD Investment Committee, Prevention Medical Review Board and ASDS Social Media Ambassador, and former member of the WDS Practice Advisory Committee, WDS Finance and Investment Committee, WDS Fundraising and Philanthropic Activities Committee, and former AAD Media Expert Team member and NPF Social Ambassador. A. Kronbergs: Shareholder/stock ownership; A.K. is an employee and shareholder at Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N.E. is an employee and shareholder at Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D.Z. is an employee and shareholder at Eli Lilly and Company. E. Mevel: Shareholder/stock ownership; E.M. is an employee and shareholder at Eli Lilly and Company. T. Holzkaemper: Shareholder/stock ownership; T.H. is an employee and shareholder at Eli Lilly and Company. E. Krishnan: Shareholder/stock ownership; E.K. is an employee and shareholder at Eli Lilly and Company. M. Lebwohl: Consultancies; M.L. also reports consulting fees from AnaptysBio, Arcutis, Inc., Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BioMX, Boehringer-Ingelheim, Brickell Biotech, Castle Biosciences,, Corevitas, Dermavant Sciences, Evommune, Inc., Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd., Meiji Seika Pharma, Mindera, National Society of Cutaneous Medicine, New York College of Podiatric Medicine, Pfizer, Seanergy, SUN Pharma, Verrica, and Vial. Grants/research support; M.L. reports grants/contracts from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc. P. Rahman: Consultancies; P.R. received consulting fees from AbbVie, Janssen, Novartis, Eli Lilly and Company and Pfizer. Grants/research support; P.R. discloses grants or contracts received from Janssen and Novartis. H. Marzo-Ortega: Consultancies; H.M-O. also discloses consulting fees from Abbvie, Eli Lilly and Company, Janssen, Moonlake, Novartis, Pfizer, and UCB. Honoraria; H.M-O. discloses payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Biogen, Eli-Lilly, Janssen, Novartis, Pfizer, and UCB. Grants/research support; H.M-O. discloses grants or contracts received from Janssen, Novartis and UCB. Other; H. M-O. additionally discloses support for attending meetings and/or travel from UCB, participation on a Data Safety Monitoring Board or Advisory Board at Pfizer, leadership or fiduciary role in other board, society (paid or unpaid) in the Executive Committee ASAS, the Medical Advisory Board of NASS and as Chair of the British Society for Spondyloarthritis. C. Bullock: Shareholder/stock ownership; C. Bullock is an employee and minor shareholder in Lilly.