POS1033 SAFETY OF IXEKIZUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS: AN INTEGRATED ANALYSIS OF 4 CLINICAL TRIALS
Authors: C. Sesin, G. Gallo, A. Gellett, A. Kronbergs, A. T. Sprabery, W. Xu, H. Patel, A. Deodhar, B. Combe, G. R. Burmester
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with psoriatic arthritis (PsA) require long-term treatment, which may lead to adverse events (AEs). Ixekizumab, an interleukin-17A antagonist, is approved for the treatment of adults with active PsA. Objectives: We report a summary of safety outcomes for patients enrolled in 4 PsA studies with up to 3 years of exposure to ixekizumab. Methods: This integrated safety analysis included all patients with PsA who received at least 1 dose of ixekizumab (80 mg every 2 or 4 weeks) in 4 clinical trials ( NCT01695239 , NCT02349295 , NCT02584855 , NCT03151551 ). Safety outcomes included treatment-emergent adverse events (TEAEs), serious AEs (SAEs), discontinuations due to AEs, deaths, and AEs of special interest. Results: A total of 1401 patients were included in this safety analysis (51.5% female; mean age 49 years), with 2247.6 patient-years of exposure (Table 1). In all, 1131 patients (80.7%) reported ≥1 TEAE (exposure-adjusted incidence rate per 100 patient-years [IR] 50.3, 95% CI 47.5–53.3), mostly mild (32.9%) or moderate (39.7%) in severity. The most common TEAEs were nasopharyngitis (n=202, IR 9.0), upper respiratory infections (n=186, IR 8.3), and injection site reaction (n=156, IR 6.9). SAEs were reported by 134 patients (IR 6.0, 95% CI 5.0–7.1). 115 (8.2%) patients discontinued due to AEs (IR 5.1, 95% CI 4.3–6.1). Six deaths were reported (IR 0.3, 95% CI 0.1–0.6). Allergic reactions/hypersensitivity were reported in 102 patients (IR 4.5, 95% CI 3.7–5.5). Three cases were adjudicated as de novo inflammatory bowel disease (IR 0.13, 95% CI 0.04–0.41); 1 was ulcerative colitis (IR 0.04, 95% CI 0.01–0.32), 2 were Crohn’s disease (IR 0.09, 95% CI 0.02–0.36). Major adverse cardiac events occurred in 12 patients (IR 0.5) and malignancies in 15 (IR 0.7), 9 of which were non-melanoma skin cancer. Opportunistic infections occurred in 40 (2.9%) patients (IR 1.8, 95% CI 1.3–2.4). Candidiasis occurred in 24 patients (oral: IR 0.7, 95% CI 0.4–1.2; oral fungal infection: IR 0.3, 95% CI 0.1–0.6; esophageal infection: IR 0.1, 95% CI 0.0–0.4). No active or reactive cases of tuberculosis were reported. Other opportunistic infections included hepatitis B (IR 0.0, 95% CI 0.0–0.3), herpes simplex (IR 1.8, 95% CI 1.3–2.5), and herpes zoster (IR 0.7, 95% CI 0.4–1.2). Conclusion: The safety profile of ixekizumab across 4 clinical trials and up to 3 years of continuous treatment in patients with active PsA was consistent with the known safety profile reported in previous studies for psoriasis and PsA. No new safety events were found in this analysis. Pooled Ixekizumab (N=1401; Total Patient-Years=2247.6 ) n (IR ) 95% CI Year 0–1 (n=1401 ) n (IR ) 95% CI Year 1–2 (n=946 ) n (IR ) 95% CI Year 2–3 (n=510 ) n (IR ) 95% CI Year ≥3 (n=89 ) n (IR ) 95% CI Total Patient-Years 2247.7 1207.3 689.8 347.7 2.9 Patients with ≥1 TEAE 1131 (50.3) 1050 (87.0) 496 (71.9) 234 (67.3) 6 (206.2) 47.5–53.3 81.9–92.4 65.9–78.5 59.2–76.5 92.6–458.9 SAEs 134 (6.0) 72 (6.0) 53 (7.7) 19 (5.5) 1 (34.4) 5.0–7.1 4.7–7.5 5.9–10.1 3.5–8.6 4.8–243.9 Discontinuations due to AEs 115 (5.1) 61 (5.1) 37 (5.4) 17 (4.9) 0 (0) 4.3–6.1 3.9–6.5 3.9–7.4 3.0–7.9 0.0–274.7 Hepatic reactions 112 (5.0) 80 (6.6) 32 (4.6) 14 (4.0) 0 (0) 4.1–6.0 5.3–8.3 3.3–6.6 2.4–6.8 0.0–274.7 Allergic reaction/hypersensitivity 102 (4.5) 83 (6.9) 23 (3.3) 5 (1.4) 0 (0) 3.7–5.5 5.5–8.5 2.2–5.0 0.6–3.5 0.0–274.7 Serious infection 28 (1.2) 18 (1.5) 9 (1.3) 3 (0.9) 0 (0) 0.9–1.8 0.9–2.4 0.7–2.5 0.3–2.7 0.0–274.7 Malignancies 15 (0.7) 4 (0.3) 8 (1.2) 4 (1.2) 0 (0) 0.4–1.1 0.1–0.9 0.6–2.3 0.4–3.1 0.0–274.7 Major adverse cardiac events 12 (0.5) 3 (0.2) 8 (1.2) 1 (0.3) 0 (0) 0.3–0.9 0.1–0.8 0.6–2.3 0.0–2.0 0.0–274.7 Inflammatory bowel disease 3 (0.1) 3 (0.2) 1 (0.1) 0 (0.0) 0 (0.0) 0.0–0.4 0.1–0.8 0.0–1.0 0.0–2.3 0.0–274.7 Ulcerative colitis 1 (0.0) 1 (0.1) 1 (0.1) 0 (0.0) 0 (0.0 ) 0.0–0.3 0.0–0.6 0.0–1.0 0.0–2.3 0.0–274.7 Crohn’s disease 2 (0.1) 2 (0.2) 0 (0.0) 0 (0.0) 0 (0.0 ) 0.0–0.4 0.0–0.7 0.0–1.2 0.0–2.3 0.0–274.7 AE, adverse event; CI, confidence interval; IR, exposure-adjusted incidence rate per 100 patient-years; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Disclosure of Interests: Carlos Sesin Speakers bureau: Amgen, AbbVie, Sanofi, Radius, Pfizer, Eli Lilly and Company, Novartis, Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Amanda Gellett Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Wen Xu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Himanshu Patel Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos, Glaxo Smith &amp; Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly and Company, Glaxo Smith &amp; Kline, Novartis, Pfizer, UCB, Bernard Combe Speakers bureau: AbbVie, BMS, Gilead-Galapagos, Eli Lilly and Company, MSD, Pfizer, Roche Chugai, Consultant of: AbbVie, Bayer, Gilead-Galapagos, Janssen, Eli Lilly and Company, Novartis, Roche Chugai, Grant/research support from: AbbVie, Eli Lilly and Company, Pfizer, Roche Chugai, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Janssen, Novartis, Eli Lilly and Company, MSD, Pfizer, Consultant of: AbbVie, Janssen, Novartis, Eli Lilly and Company, MSD, Pfizer.