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

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.

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure.

INTRODUCTION: We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab. METHODS: Long-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated. RESULTS: A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time. CONCLUSIONS: The long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected.