Withdrawing Ixekizumab in Patients with Psoriatic Arthritis who Achieved Minimal Disease Activity: Results from a Randomized, Double-Blind Withdrawal Study

Objective: To evaluate the effect of withdrawing ixekizumab in patients with psoriatic arthritis (PsA) who had achieved minimal disease activity (MDA) after open-label ixekizumab treatment.

Methods: SPIRIT-P3 was a multicenter, randomized, double-blind withdrawal study that enrolled biologic-naive adult patients with PsA to open-label ixekizumab (160 mg at week 0, 80 mg every two weeks [IXE Q2W]) for 36 weeks. Patients sustaining MDA for >3 consecutive months were randomized (between weeks 36-64) 1:1 to blinded IXE Q2W withdrawal (placebo) or continued IXE Q2W treatment up to week 104. The primary efficacy endpoint was time to relapse (loss of MDA) for randomized patients. Patients who relapsed were retreated with IXE Q2W until week 104.

Results: A total of 394 patients were enrolled and received open-label IXE Q2W. Of those, 158 (40%) patients achieved sustained MDA and were randomized to IXE Q2W withdrawal (placebo; N=79) or continued IXE Q2W treatment (N=79). Patients relapsed more rapidly with treatment withdrawal (median 22.3 weeks [95% CI 16.1-28.3]) vs continued IXE Q2W treatment (median not estimable, p<0.0001); 67 (85%) patients vs 30 (38%) patients relapsed, respectively. Median time to re-achieving MDA on retreatment was 4.1 weeks (95% CI 4.1-4.3); 64 (96%) of 67 patients who relapsed with treatment withdrawal re-achieved MDA on retreatment. Safety was consistent with the known safety profile for ixekizumab.

Conclusion: Continued ixekizumab therapy is superior to ixekizumab withdrawal in maintaining low disease activity in biologic-naive patients with PsA. Retreatment with ixekizumab following relapse may restore disease control in case of treatment interruption.