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

Abstract

Objective: To 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.

Methods: SPIRIT-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.

Results: A 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.

Conclusion: Continued 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.

Trial registration: ClinicalTrials.gov NCT02584855.

© 2021 Eli Lilly and Company. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Figures

Figure 1

SPIRIT‐P3 study design. a Encompassed week 0 (study baseline) up to week 36. b Between weeks 36 and 64 (inclusive), patients treated with ixekizumab (IXE) every 2 weeks (Q2W) in whom minimal disease activity (MDA) was achieved for 4 consecutive visits for at least 36 weeks were eligible for randomization at the visit at which these criteria were met. Patients were randomized 1:1 to the ixekizumab every 2 weeks group or the ixekizumab withdrawal group. Patients remained in their treatment groups up to week 104 or until relapse (no longer met MDA), at which point they received ixekizumab every 2 weeks up to week 104. c Patients who did not meet the randomization eligibility criteria by week 64 continued to receive ixekizumab every 2 weeks uninterrupted up to week 104. d Patients in whom ≥20% improvement in tender joint count and swollen joint count at week 24 or at any subsequent visit through week 104, except from the point of randomization until the visit after relapse for patients in the randomized double‐blind withdrawal period, were discontinued from the study. PBO = placebo.

Figure 2

Time to relapse (loss of MDA) in the randomized withdrawal intent‐to‐treat population. ‡P < 0.0001 versus ixekizumab withdrawal. 95% CI = 95% confidence interval; NE = not estimable (see Figure 1 for other definitions).

Figure 3

Loss of response for individual components of MDA in the randomized withdrawal intent‐to‐treat population. P values were determined by adjusted log rank test after stratification by geographic region and use of conventional synthetic disease‐modifying antirheumatic drugs. TJC = tender joint count; SJC = swollen joint count; PASI = Psoriasis Area and Severity Index; BSA = body surface area affected by psoriasis; VAS = visual analog scale; HAQ DI = Health Assessment Questionnaire disability index; Nx = the number of patients who met the MDA component at randomization and subsequently lost the response (see Figure 1 for other definitions).

Figure 4

Time to reachievement of MDA following relapse (A) or reachievement of sustained MDA (≥4 visits over 3 consecutive months) following relapse (B). Week 0 represents re‐treatment. Data were available through week 40 in A and through week 60 in B. 95% CI = 95% confidence interval (see Figure 1 for other definitions).