Efficacy and safety of risankizumab for active psoriatic arthritis: 100-week results from the KEEPsAKE 1 and KEEPsAKE 2 trials

Background: We evaluate Risankizumab (RZB), a monoclonal antibody specifically inhibiting IL‐23, versus placebo (PBO), for efficacy and safety in adults with active PsA in the ongoing Phase 3 KEEPsAKE‐1 and 2 trials. Methods: KEEPsAKE‐1 and 2 enrolled adults with active PsA and plaque or nail psoriasis. KEEPsAKE‐1 patients had inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drug(csDMARD‐IR). KEEPsAKE‐2 enrolled csDMARD‐IR and/or patients with inadequate response or intolerance to one or two biologic therapies (Bio‐IR). Patients randomized 1:1 received blinded subcutaneous RZB 150 mg or PBO at weeks(W) 0, 4, and 16. At W24, all patients received open‐label RZB 150 mg every 12 Wks. Efficacy and safety were analyzed in patients receiving 1 or more doses of study drug through W100. Treatment‐emergent adverse events (TEAEs) were summarized using exposure‐adjusted event rates (EAERs, events/100 patient‐years[PYs]). Results: At W100, patients in KEEPsSAKE‐1 (RZB N=483; PBO/RZB N=481) and KEEPsAKE‐2 (RZB N=224; PBO/RZB N=219) had similar results to those reported at W52. Achievement of ACR20, 50, and 70 overtime results for both studies will be presented. In KEEPsAKE‐1, ACR20 at W100 was achieved by 64.3 percent and 62.1 percent of RZB and PBO/RZB patients, respectively. In KEEPsAKE‐2, 57.1 percent of RZB and 52.5 percent of PBO/RZB patients achieved ACR20 at W100. In KEEPsAKE‐1, 71.3 percent of RZB and 67.8 percent of PBO/ RZB patients achieved PASI 90. In KEEPsAKE‐2, 67.5 percent of RZB and 61.3 percent of PBO/RZB patients achieved PASI 90. Patients also maintained HAQ‐DI scores in both KEEPsAKE‐1 (RZB ‐0.41, PBO/ RZB ‐0.36) and KEEPsAKE‐2 (RZB ‐0.26, PBO/RZB ‐0.31). For patients with nail psoriasis at baseline both PGA‐F scores (KEEPsAKE‐1 RZB ‐1.4, PBO/RZB ‐1.3) and mNAPSI scores (KEEPsAKE‐1 RZB ‐11.33, PBO/RZB ‐13.54) were maintained. Resolution of enthesitis at baseline was seen in 60.6% of RZB and 62.1 percent of PBO/RZB patients in KEEPsAKE‐1 and 51.7 percent of RZB and 53.2 percent of PBO/ RZB patients in KEEPsAKE‐2. Resolution of dactylitis at baseline was seen in 75.4 percent of RZB and 77.9 percent of PBO/RZB KEEPsAKE‐1 patients and 77.5 percent of RZB and 68.4 percent of RZB/PBO patients in KEEPsAKE‐2. As of the W100 cut‐off, EAERs of any TEAE was 130.1/100PY(KEEPsAKE‐1) and 180.5/100PYin(KEEPsAKE‐2). Conclusion: Long term treatment with RZB provides durable efficacy response in PsA through 100 weeks. RZB was generally well tolerated, with no new safety signals.