P261 Continuing versus withdrawing ixekizumab in patients with PsA who achieved sustained minimal disease activity: results from the SPIRIT-P3 study

Abstract

Abstract Background This study evaluated efficacy and safety of continuing vs. withdrawing ixekizumab (IXE), an IL-17A antagonist, in psoriatic arthritis (PsA) patients who achieved sustained minimal disease activity (MDA) on IXE and re-treating with IXE if required. Methods SPIRIT-P3 (NCT02584855) was a multicentre phase 3b study enrolling biologic-naïve patients with active PsA (diagnosis for ≥6 months, meeting classification criteria for psoriatic arthritis, ≥3/68 tender joints, ≥3/66 swollen joints) and previous inadequate response to conventional synthetic DMARDs (csDMARDs). Patients entered a 36-week, open-label (OL) treatment period with IXE every 2 weeks. Between Weeks 36-64, patients were randomised 1:1 to IXE or placebo (PBO) at the visit for which randomisation criteria were met (sustained MDA for at least 4 visits over 3 consecutive months) and evaluated up to Week 104. Patients not meeting randomisation criteria by Week 64 continued IXE up to Week 104. Maintenance of treatment response was measured by time to loss of sustained MDA (relapse) during randomised withdrawal (RW) period. The proportion of patients who relapsed during the first 40 weeks of RW period and time to regain MDA after re-treatment with IXE in relapsed patients were assessed. The Kaplan-Meier product limit method was used to estimate survival curves for time-to variables. Treatment comparisons were performed using a log-rank test adjusting for geographic region and csDMARD use as factors. Cumulative proportion of relapse was analysed using a logistic regression model with treatment, geographic region, and csDMARD use as factors. Safety data were summarised for the entire study period for patients who received ≥1 dose of IXE. Results In total, 394 patients entered the OL treatment period; 158 (40%) achieved sustained MDA criteria and were randomised to IXE (N = 79) or PBO (N = 79). Baseline characteristics were similar between groups. Time to relapse on PBO was significantly shorter than for IXE (p < 0.001) during RW period, with a median time to relapse of 22.3 weeks in the PBO group. The cumulative relapse rate during the first 40 weeks of RW period was 73% for PBO vs. 34% for IXE (p < 0.001). Of those who relapsed on PBO, 96% regained MDA following re-treatment with IXE. The median time to regain MDA was 4.1 weeks (95%CI 4.14-4.29) for PBO and 4.7 weeks (95%CI 4.14-8.29) for IXE. Safety data were consistent with previous IXE PsA studies with no unexpected safety signals. Conclusion Continued IXE therapy was superior to PBO in maintaining MDA in biologic-naïve PsA pts who achieved sustained MDA on initial IXE treatment. A vast majority of patients who lost MDA after IXE withdrawal regained MDA with IXE re-treatment. Continuous IXE treatment is optimal for maintaining MDA; however, patients can regain MDA after re-treatment with IXE in case of treatment interruption. Disclosures L.C. Coates: Corporate appointments; L. Coates is a consultant for: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen, MSD, Novartis, Pfizer, Prothena, Sun Pharma, and UCB. Consultancies: L. Coates is a consultant for: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen, MSD, Novartis, Pfizer, Prothena, Sun Pharma, and UCB. S.G. Pillai: Corporate appointments; S.G.P. is an employee and shareholder of Eli Lilly and Company. L. Zhang: Corporate appointments; Employee and shareholder of Eli Lilly and Company. D. Adams: Corporate appointments; Employee and shareholder of Eli Lilly and Company. L. Kerr: Corporate appointments; Employee and shareholder of Eli Lilly and Company. M. Hojnik: Corporate appointments; Employee and shareholder of Eli Lilly and Company. G. Gallo: Corporate appointments; Employee and shareholder of Eli Lilly and Company. I. Valter: None. H. Tahir: Grants/research support; H. Tahir has received grants/research support from: AbbVie, Celgene, Eli Lilly and Company, Janssen, and Novartis. V. Chandran: Grants/research support; V. Chandran has received grant/research support from AbbVie, is a consultant for: AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB. P. Mease: Consultancies; P. J. Mease is a consultant for and has received grant/research support from: AbbVie, Amgen, BMS, Celgene, Crescendo, Eli Lilly and Company, Genentech, Janssen, Merck, Novartis, Pfizer, UCB, is on the. A. Kavanaugh: Consultancies; A. Kavanaugh is a consultant for Eli Lilly and Company.