FRI0359 INTEGRATED SAFETY RESULTS OF TWO PHASE-3 TRIALS OF GUSELKUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS THROUGH THE PLACEBO-CONTROLLED PERIODS
Authors: P. Rahman, C. T. Ritchlin, P. Helliwell, W. H. Boehncke, P. J. Mease, A. B. Gottlieb, S. Kafka, A. Kollmeier, E. C. Hsia, X. L. Xu, M. Shawi, S. Sheng, P. Agarwal, B. Zhou, P. Ramachandran, I. Mcinnes
Journal: Annals of the Rheumatic Diseases (2020)

Background: DISCOVER 1 &amp; 2 are phase 3 psoriatic arthritis (PsA) trials investigating guselkumab (GUS), an IL-23 inhibitor that specifically binds the IL-23p19 subunit. In both studies, GUS showed significant improvement vs placebo (PBO) through week (W) 24 in the PBO-controlled period. 1,2 Objectives: To present integrated safety results of DISC 1 &amp; 2 through the PBO-controlled periods. Methods: Adult patients (pts) with active PsA despite standard therapy were enrolled. All pts were biologic-naïve, except ~30% in DISC 1 with previous exposure to 1-2 TNF inhibitors. Pts were randomized to SC GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. Adverse events (AEs) and lab results were analyzed from pooled data. Results: The rates of pts experiencing ≥1 AE, serious AE, infection, serious infection, and discontinuation due to an AE were similar between GUS and PBO (Table 1). There were 2 deaths, 3 malignancies, 2 Major Adverse Cardiac Events (MACE), and no opportunistic infections (treatment group not shown to prevent unblinding). Among the AEs reported by ≥5% pts in any group (Table 1), nasopharyngitis and elevated serum hepatic aminotransferases were more common with GUS vs PBO. Laboratory ALT and AST elevations were mostly mild, transient, and not associated with significant bilirubin elevation. There was a trend to decreased neutrophil count (mostly Grade 1, transient, and not associated with infection) with GUS vs PBO (Table 2). Low rates of injection-site reactions were seen with GUS vs PBO. Anti-drug antibody development was also low (Table 1). Table 1. Patient Reported AEs, n (%) GUS 100 mg Q8W GUS 100 mg Q4W PBO N 375 373 372 ≥1 AE 182 (48.5) 182 (48.8) 176 (47.3) ≥1 Serious AE 7 (1.9) 8 (2.1) 12 (3.2) Discontinuation due to AE 5 (1.3) 8 (2.1) 7 (1.9) ≥1 Infection 73 (19.5) 80 (21.4) 77 (20.7) ≥1 Serious infection 1 (0.3) 3 (0.8) 3 (0.8) ≥1 Opportunistic Infection (including Candida) 0 0 0 Active Tuberculosis 0 0 0 ≥1 Injection-site reaction 5 (1.3) 4 (1.1) 1 (0.3) Anti-GUS antibody +, n/N (%) 6/373 (1.6) 9/371 (2.4) -- AEs* reported by ≥5% of patients in any treatment group Nasopharyngitis 26 (6.9) 19 (5.1) 17 (4.6) Upper respiratory tract infection 13 (3.5) 23 (6.2) 17 (4.6) Increased ALT 23 (6.1) 28 (7.5) 14 (3.8) Increased AST 23 (6.1) 14 (3.8) 9 (2.4) * Medical Dictionary for Regulatory Activities (MedDRA) preferred term Table 2. Lab Results* GUS 100 mg Q8W GUS 100 mg Q4W PBO N 373 371 370 ALT Increased (%) Grade 1 28.2 35.0 30.1 2 1.1 2.7 1.4 3-4 0.8 1.1 0.8 Neutrophil Count Decreased (%) Grade 1 5.6 5.9 3.2 2 1.6 1.6 0.8 3-4 0 0.3 0.3 * NCI toxicity grade ALT=Alanine aminotransferase Conclusion: GUS was safe and well tolerated through the PBO-controlled period in 2 randomized, phase 3 trials of patients with active PsA. There were no meaningful safety differences between the Q8W and Q4W groups, no significant safety issues identified when comparing GUS to PBO, and no safety signals with regards to infections, malignancy, and MACE. The safety profile of GUS Q4W and Q8W in PsA pts was generally consistent with that in the Phase 3 trials of GUS Q8W for psoriasis. 3,4 References: [1]Deodhar et al. ACR 2019 (#807). Arth Rheum 2019;71 S10:1386 [2]Mease et al. ACR 2019 (#L13). Arth Rheum 2019;71 S10:5247 [3]Blauvelt et al. J Am Acad Derm 2017;76:405 [4]Reich et al. J Am Acad Derm 2017;76:418 Acknowledgments: None Disclosure of Interests: Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research &amp; Development, LLC, Consultant of: Janssen, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Prasheen Agarwal Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Bei Zhou Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Paraneedharan Ramachandran Employee of: Janssen Research &amp; Development, LLC, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB