Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure

Abstract

Objectives: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A (IL-17A), has shown significant efficacy in the treatment of psoriatic arthritis (PsA) and sustained long-term clinical response without unexpected new safety outcome for an IL-17A inhibitor. Here, we report the updated safety profile of ixekizumab up to 3 years in patients with PsA.

Methods: This is an integrated safety analysis from four clinical trials in patients with PsA who received at least one dose of ixekizumab. Treatment-emergent adverse events (TEAEs) and selected adverse events (AEs) exposure-adjusted incidence rates (EAIRs) per 100 patient-years up to 3 years of exposure are reported.

Results: A total of 1401 patients with a cumulative ixekizumab exposure of 2247.7 patient-years were included in this analysis. The EAIR of patients with ≥1 TEAE was 50.3 per 100 patient-years and most TEAEs were mild to moderate in severity. Serious AEs were reported by 134 patients (EAIR=6.0). The most reported TEAEs were nasopharyngitis (EAIR=9.0) and upper respiratory tract infection (EAIR=8.3). Infections in general and injection site reactions were the most common TEAEs; the incidence rates of serious cases were low (EAIR ≤1.2). The EAIRs of malignancies (EAIR=0.7), inflammatory bowel disease (EAIR=0.1) including ulcerative colitis and Crohn's disease, depression (EAIR=1.6), and major adverse cerebro-cardiovascular events (EAIR=0.5) were low. As assessed, based on year of exposure, incidence rates were decreasing or constant over time.

Conclusions: In this analysis, the overall safety profile and tolerability of ixekizumab are consistent with the known safety profile in patients with PsA. No new or unexpected safety events were detected.

Trial registration number: NCT01695239, NCT02349295, NCT02584855, NCT03151551.

Keywords: Biological Therapy; Inflammation; Psoriatic Arthritis; Therapeutics.

Conflict of interest statement

Competing interests: AAD reports consulting and advisory boards for AbbVie, Amgen, Aurinia, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer and UCB; and research grants from AbbVie, Eli Lilly and Company, GlaxoSmithKline, Novartis, Pfizer and UCB. BC has received grant/research support from Novartis, Pfizer and Roche-Chugai; served as a consultant for AbbVie, Eli Lilly and Company, Gilead Sciences, Janssen, Pfizer, Roche-Chugai and Sanofi; and served on speakers’ bureaus for Bristol Myers Squibb, Eli Lilly and Company, Gilead Sciences, Merck Sharp & Dohme, Pfizer and Roche-Chugai. APA, DZ, RB, AMG and ATS are shareholders and employees of Eli Lilly and Company. G-RRB is a consultant for Eli Lilly and Company, Janssen, Novartis and Pfizer; and has received research funding from Eli Lilly and Company.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Exposure-adjusted incidence rate of (A) TEAEs, (B) SAEs and (C) discontinuation due to AEs (exposure safety populations). The data points on the graph are the EAIR (95% CI)/100 patient-years at successive year intervals from year 0 to year 3. The CIs for the EAIR are from the likelihood ratio test of treatment effect from the Poisson regression model. AE, adverse event; EAIR, exposure-adjusted incidence rate; IR, incidence rate; PY, patient-years; SAE, serious adverse events; TEAE, treatment-emergent adverse event.

Figure 2

Exposure-adjusted incidence rate of selected adverse events including (A) serious infections, (B) ISR, (C) malignancies, (D) IBD, (E) depression, and (F) MACE. The data points on the graph are the EAIR (95% CI)/100 patient-years at successive year intervals from year 0 to year 5. The CIs for the EAIRs are from the likelihood ratio test of treatment effect from the Poisson regression model. aData represent cases classified as ‘definite’ and ‘probable’ per external adjudication. Three patients had events of IBD confirmed by adjudication. One patient had more than one event. bData represent events confirmed after adjudication. EAIR, exposure-adjusted incidence rates; IBD, inflammatory bowel disease; IR, incidence rate; ISR, injection site reactions; MACE, major adverse cardiovascular events; PY, patient-years.