Long-Term Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 316-Week Results from the KEEPsAKE 2 Trial

Introduction & Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment to manage symptoms across multiple disease domains. Risankizumab (RZB), a humanized IgG1 monoclonal antibody targeting the p19 subunit of interleukin-23, has shown efficacy across multiple PsA disease domains. Here, we report final long-term efficacy and safety outcomes through 316 weeks (6 years) of the KEEPsAKE 2 (KS2) trial. Materials & Methods: KS2 (NCT03671148) is an ongoing, multicenter, clinical study in patients with active PsA and prior intolerance or inadequate response to 1 to 2 biological disease-modifying antirheumatic drugs (bDMARDs) and/or ≥1 conventional synthetic DMARD (csDMARDs). Patients were randomized 1:1 to receive RZB 150 mg or placebo (PBO) for a 24-week, double-blind period, after which all patients received open-label RZB at week 28 and every 12 weeks thereafter. Long-term efficacy and safety were assessed in all patients who received ≥1 dose of RZB. Categorical endpoints are reported with nonresponder imputation with multiple imputation (NRI-MI), except Leeds Dactylitis Index (LDI), which is reported as observed (AO). Continuous endpoints are reported with mixed-effect model repeated measurements (MMRM). Safety events are summarized as exposure-adjusted event rates (EAERs) and reported as events per 100 patient-years (E/100 PY). Results: A total of 444 patients were randomized and 443 received treatment (224 to RZB, 219 to PBO). Patients receiving open-label RZB displayed sustained efficacy through weeks 24, 52, 148, 244, and 316. At week 316, ACR20 was achieved by 45.1% of those receiving continuous RZB and 38.8% of patients who switched from PBO to RZB (PBO/RZB). ACR50 was achieved by 28.6% of patients on RZB and 23.7% on PBO/RZB, and ACR70 was achieved by 17.0% and 15.5% of patients on RZB and PBO/RZB, respectively. Minimal disease activity (MDA) was achieved by patients receiving RZB (26.3%) and PBO/RZB (26.5%). Among patients with psoriasis affecting ≥3% of body surface area at baseline, 58.5% and 49.6% on RZB and PBO/RZB, respectively, achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at week 316. For patients with enthesitis or dactylitis at baseline, resolution of enthesitis (Leeds Enthesitis Index [LEI]=0) was achieved by 42.9% of those on RZB and 42.4% on PBO/RZB. Resolution of dactylitis (LDI=0) was achieved by 96.2% of patients receiving RZB and by 100% of those receiving PBO/RZB, as reported by AO. Clinically meaningful improvement in the Health Assessment Questionnaire-Disability Index (HAQ-DI, ≥0.35 decrease from baseline) was achieved by 33.2% of patients on RZB and 31.6% of those on PBO/RZB. At week 316, the rates for all treatment-emergent adverse events (TEAEs; 160.0 E/100 PY), serious TEAEs (9.5 E/100 PY), and TEAEs leading to discontinuation of study drug (1.7 E/100 PY) were consistent with those reported at week 24. Conclusion: Long-term treatment with RZB 150 mg every 12 weeks provided sustained efficacy and a consistent safety profile through 316 weeks for adults with active PsA with an intolerance or inadequate response to bDMARDs and/or csDMARDs.