Long-Term Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 2 Trial

Abstract

Introduction & Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 of the KEEPsAKE 2 trial. 

Materials & Methods: Adult patients with previous inadequate response or intolerance to 1 or 2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) were randomized in a 1:1 ratio to subcutaneous RZB 150mg or matched placebo for a 24-week double-blind placebo controlled period. Starting at week 28, patients received open-label RZB every 12 weeks thereafter. Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug. Statistical approaches included non-responder imputation incorporating multiple imputation (NRI-MI) for binary endpoints, and mixed-effect model for repeated measures (MMRM) for categorical endpoints at week 196. Safety assessments based on treatment emergent adverse events (TEAEs) are summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [E/100PYs]).

Results: 51.3% of patients on RZB 150mg (N=224) achieved the primary endpoint of ACR20 at week 24 compared to 26.5% on placebo (N=219). Patients on open-label RZB maintained similar efficacy results at week 196 as those reported previously at weeks 24, 52, 100, and 148. At week 196, 54.5% patients receiving continuous RZB and 50.2% patients on PBO/RZB achieved ACR20; 35.3% on RZB and 37.0% on PBO/RZB achieved ACR50; 35.3% on RZB and 37.4% on PBO/RZB achieved minimal disease activity (MDA). In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 66.7% on RZB and 56.3% on PBO/RZB achieved PASI90 at week 196. In patients with enthesitis at baseline, 49.0% on RZB and 50.0% on PBO/RZB achieved resolution. In patients with dactylitis at baseline, 75.0% on RZB and 59.6% on PBO/RZB achieved resolution. Among patients with HAQ-DI scores of at least 0.35 at baseline, 36.7% on RZB and 40.6% on PBO/RZB achieved improvements of at least 0.35 at week 196. The overall rates of TEAEs (170.7 E/100PYs), serious TEAEs (9.8 E/100PYs) and AEs leading to discontinuation of study drug (1.4 E/100PYs) remained stable and consistent with rates reported previously at week 24 for the placebo-controlled period, and weeks 52, 100, and 148.

Conclusion: The 196-week results from KEEPsAKE 2 demonstrate that long-term treatment with RZB shows durable efficacy in Bio-IR and/or csDMARD-IR patients with PsA, with no new safety findings.