Long-Term Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 244-Week Results From the KEEPsAKE 2 Trial

Introduction & Objectives: This analysis aimed to assess the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 244 of the KEEPsAKE 2 trial. Materials & Methods: KEEPsAKE 2 is an ongoing, multicenter, phase 3 clinical trial in patients with active PsA and previous intolerance or inadequate response to 1 or 2 biological therapies (Bio-IR) and/or ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Patients were randomized 1:1 to receive RZB 150 mg or placebo (PBO) for a 24-week double-blind period. By week 28, all patients were switched to open-label RZB and administered the study drug every 12 weeks thereafter. Safety and efficacy were assessed in all patients who received ≥ 1 dose of RZB. Statistical analyses included nonresponder imputation incorporating multiple imputation (NRI-MI) for binary endpoints and multiple mixed response model (MMRM) for continuous endpoints. Safety assessments based on treatment-emergent adverse events (TEAEs) are summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [E/100PYs]). Results: Patients on open-label RZB maintained similar efficacy results at week 244 as those reported previously at weeks 24, 52, 100, 148, and 196. At week 244, 49.6% of patients initially randomized to RZB and 42.9% of patients who switched from PBO to RZB (PBO/RZB) achieved ACR20; 30.4% on RZB and 28.3% on PBO/RZB achieved ACR50; 19.2% on RZB and 15.5% on PBO/RZB achieved ACR70; 29.9% on RZB and 27.4% on PBO/RZB achieved minimal disease activity (MDA). Among patients with baseline psoriasis severity affecting ≥ 3% body surface area, 61.8% on RZB and 52.1% on PBO/RZB achieved a 90% improvement in psoriasis area severity index (PASI90). Among patients with enthesitis or dactylitis at baseline, 45.6% on RZB and 42.4% on PBO/RZB achieved resolution of enthesitis (Leeds Enthesitis Index = 0), and 70.0% on RZB and 47.4% on PBO/RZB achieved resolution of dactylitis (Leeds Dactylitis Index = 0). For patients with a baseline HAQ-DI score ≥ 0.35, clinically meaningful improvements occurred in 33.2% on RZB and 32.1% on PBO/RZB. Week 244 safety assessments were consistent with those from the 24-week placebo-controlled study and through the open-label extension period: overall TEAEs (165.8 E/100PYs), serious TEAEs (9.7 E/100PYs), and any TEAE leading to discontinuation of RZB (1.5 E/100PYs). Conclusion: Long-term treatment with RZB demonstrates durable efficacy and a consistent safety profile through 244 weeks for adult patients with active PsA and inadequate response to biological therapies and/or csDMARD(s).