AB0802 SAFETY PROFILES OF IXEKIZUMAB VERSUS ADALIMUMAB: 52-WEEK RESULTS FROM A HEAD-TO-HEAD COMPARISON IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS
Authors: P. J. Mease, J. S. Smolen, A. Kavanaugh, P. Nash, G. Gallo, S. Liu Leage, C. Sapin, M. C. Genovese
Journal: Annals of the Rheumatic Diseases (2020)

Background: Ixekizumab (IXE) was shown to be superior to adalimumab (ADA) in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with active psoriatic arthritis (PsA) and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). 1 Objectives: To compare the safety and tolerability profile of IXE vs ADA in patients with PsA up to 52 weeks of treatment. Methods: SPIRIT-H2H ( NCT03151551 ) was an open-label, head-to-head, blinded assessor clinical trial which included patients with active PsA (≥3 tender joint count + ≥3 swollen joint count) and plaque psoriasis (BSA ≥3%) who were inadequate responders to csDMARD therapy but naïve to biologic DMARDs. Patients were randomized (1:1) to approved dosing of IXE or ADA. Safety events were assessed at each patient visit up to Week 52. Frequencies of adverse events (AEs) were based on the number of patients in the safety population (patients who received ≥1 dose of study drug). Cases of inflammatory bowel disease (IBD) and cerebro-cardiovascular events were adjudicated by external committees. Kaplan-Meier analysis of time to onset of serious adverse events (SAEs) was performed. Results: Of the 283 patients randomized to each treatment, 87% (246/283) of patients who received IXE and 84% (237/283) of patients who received ADA completed 52 weeks of treatment. The frequency of treatment-emergent AEs (TEAEs) was similar between the groups (74% IXE vs 69% ADA), however fewer severe TEAEs were reported in the IXE group (3.2% IXE vs 7.1% ADA) (Table). SAEs were significantly more frequent in the ADA group compared to the IXE group (12% vs 4.2%; p&lt;0.001), and the time to develop a patient’s first SAE was significantly shorter for ADA versus IXE (p&lt;0.001; Figure). Discontinuations due to AEs were numerically more frequent in the ADA group versus the IXE group (7.4% vs 4.2%; p=0.15). IXE-treated patients reported more injection-site reactions (ISR) than ADA-treated patients (11% vs. 3.5%; p=0.002). Study withdrawals due to ISR were comparable, and only one injection-site reaction was severe on ADA (Table). There were two IBD cases reported for IXE; one case was confirmed as IBD. Conclusion: Safety results were consistent with previous trials with IXE and ADA. Compared with IXE, patients with PsA treated with ADA had significantly more serious AEs. References: [1]Mease PJ, et al. Ann Rheum Dis. 2020;79(1):123-31. Table. Safety results at 52 weeks IXE N=283 n (% ) ADA N=283 n (% ) TEAEs 209 (74) 194 (69) Severe a 9 (3.2) 20 (7.1) Related to study treatment b 98 (35) 87 (31) Serious adverse events 12 (4.2) 35 (12)*** Deaths 0 0 Discontinuation due to AE 12 (4.2) 21 (7.4) Serious infections 3 (1.1) 4 (1.4) Injection-site reactions c 30 (11) 10 (3.5)** Severe 0 1 (0.4) Resulted in discontinuation 2 (0.7) 3 (1.1) Anaphylaxis 0 0 Inflammatory bowel disease 2 (0.7) 0 Ulcerative colitis 1 (0.4) d 0 Crohn’s disease 1 (0.4) 0 Cerebro-cardiovascular events 5 (1.8) 7 (2.5) MACE 0 2 (0.7) Malignancies 0 4 (1.4) Depression 5 (1.8) 9 (3.2) Interstitial lung disease 0 1 (0.4) Cytopenias 9 (3.2) 12 (4.2) Hepatic events 18 (6.4) 20 (7.1) a Patients with multiple occurrences of the same event are counted under the highest severity. b The TEAE’s relationship to study treatment was judged by the investigator. c MedDRA high-level term. d This event was adjudicated but it was not a confirmed IBD. ***p&lt;0.001; **p&lt;0.01 by Fisher’s exact test. ADA=adalimumab, AE=adverse event; IBD=inflammatory bowel disease; IXE=ixekizumab; MACE=major adverse cardiovascular event; TEAE=treatment-emergent adverse event. Disclosure of Interests: Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme