Withdrawing Ixekizumab in Patients With Psoriatic Arthritis Who Achieved Minimal Disease Activity: Results From a Randomized, Double-Blind Withdrawal Study.

Abstract

ObjectiveTo evaluate the effect of withdrawing ixekizumab in patients with psoriatic arthritis (PsA) in whom minimal disease activity (MDA) has been achieved after open‐label ixekizumab treatment.MethodsSPIRIT‐P3 was a multicenter, randomized, double‐blind withdrawal study of biologic treatment–naive adult patients with PsA who were treated with open‐label ixekizumab for 36 weeks (160 mg at week 0, then 80 mg every 2 weeks). Patients in whom MDA was sustained for >3 consecutive months were randomized 1:1, between weeks 36 and 64, to undergo blinded withdrawal of ixekizumab treatment (placebo) or to continue ixekizumab treatment every 2 weeks up to week 104. The primary efficacy end point was time to relapse (loss of MDA) for randomized patients. Patients who experienced a relapse were re‐treated with ixekizumab every 2 weeks up to week 104.ResultsA total of 394 patients were enrolled and received open‐label ixekizumab every 2 weeks. Of those patients, 158 (40%) achieved sustained MDA and were randomized to undergo withdrawal of ixekizumab treatment (placebo every 2 weeks; n = 79) or to continue ixekizumab treatment every 2 weeks (n = 79). Disease relapse occurred more rapidly with treatment withdrawal (median 22.3 weeks [95% confidence interval (95% CI) 16.1–28.3]) compared to those who continued treatment with ixekizumab (median not estimable; P < 0.0001). Sixty‐seven patients (85%) compared to 30 patients (38%) experienced relapse in the placebo group and the continued treatment group, respectively. Median time to achieving MDA again with re‐treatment was 4.1 weeks (95% CI 4.1–4.3); in 64 of 67 patients (96%) who experienced relapse with treatment withdrawal, MDA was achieved again with re‐treatment. Safety was consistent with the known safety profile for ixekizumab.ConclusionContinued ixekizumab therapy is superior to ixekizumab withdrawal in maintaining low disease activity in biologic treatment–naive patients with PsA. Re‐treatment with ixekizumab following a relapse may restore disease control in cases of treatment interruption.