SAT0410 EFFICACY AND SAFETY OF IXEKIZUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS BASED ON CONCOMITANT CONVENTIONAL DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (CDMARD) USE: RESULTS FROM SPIRIT-P1 AND SPIRIT-P2

Background: Biologic disease-modifying antirheumatic drugs such as ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, are commonly prescribed to patients with psoriatic arthritis (PsA) in combination with conventional synthetic disease-modifying antirheumatic drugs (cDMARDs). Previous studies have shown that, after 24 weeks of treatment, IXE is efficacious with or without concomitant cDMARD therapy in patients with active PsA.1,2 However, there is limited evidence demonstrating efficacy and safety after 3 years of treatment. Objectives: To evaluate the long-term (3-year) efficacy and safety of IXE in patients with active PsA from SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) based on concomitant cDMARD use. Methods: Patients were subdivided into the following subgroups: 1) no cDMARD use for 3 years (ixekizumab monotherapy); 2) methotrexate (MTX) use without interruption (i.e., ≤14-day gap of not using MTX), but allowing a change of MTX dose; and 3) any cDMARD (MTX, sulfasalazine, leflunomide, ciclosporin, hydroxychloroquine) use during 3 years without interruption (i.e., ≤14-day gap of not using cDMARDs), but allowing a switch of cDMARD type and/or change of dose. The post-hoc integrated analysis assessed efficacy and safety up to 3 years by three subgroups. Efficacy outcomes included the American College of Rheumatology (ACR) 20/50/70, Psoriasis Area and Severity Index (PASI) 75/90/100, Health Assessment Questionnaire-Disability Index (HAQ-DI) ≥0.35-point improvement. Missing data were imputed using modified non-responder imputation. The IXE 80 mg every 4 weeks (IXEQ4W) dose data are reported here. Results: Overall, IXE-treated patients showed improvement in all efficacy outcomes over 156 weeks, regardless of concomitant cDMARD use. ACR response rates by concomitant cDMARD use at 156 weeks are highlighted in Figure 1. Patients treated with IXEQ4W in the no cDMARD use, MTX, and any cDMARD use subgroups had similar ACR20 (59.1%, 67.0%, and 66.1%, respectively), ACR50 (46.2%, 47.4%, and 46.8%, respectively), and ACR70 (30.7%, 28.4%, and 28.1%, respectively) response rates at 156 weeks. Patients treated with IXEQ4W in the three subgroups also had similar PASI75 (65.5%, 60.8%, and 59.8%, respectively), PASI90 (53.6%, 49.7%, and 48.0%, respectively), and PASI100 (42.2%, 46.2%, and 42.4%, respectively) response rates at 156 weeks. The proportion of patients achieving HAQ-DI improvement ≥0.35 in the three subgroups (51.9%, 45.0%, and 47.5%, respectively) was comparable. The safety profile of IXEQ4W was consistent with that previously reported.1,2 A similar proportion of IXEQ4W-treated patients in the three subgroups reported ≥1 treatment-emergent adverse events (TEAEs) regardless of the addition of MTX or other cDMARDs (91.0%, 84.1%, and 83.2%, respectively), and the majority of TEAEs were mild or moderate in all three subgroups. Conclusion: IXEQ4W provided sustained improvements in the signs and symptoms of active PsA. While there are some numerical differences in ACR20/50/70 as well as PASI75/90/100, the overall responses with or without the addition of MTX or other cDMARDs were similar. In this post-hoc analysis, it appears that, for sustained responses over time, IXEQ4W does not require the addition of MTX or other cDMARDs. Addition of MTX or other cDMARDs to IXEQ4W did not negatively impact its favorable long-term safety profile. References: [1]Coates LC, Kishimoto M, Gottlieb A, et al. RMD Open 2017. [2]Nash P, Behrens F, Orbai A-M, et al. RMD Open 2018. Disclosure of Interests: Laura C Coates: None declared, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, So Young Park Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB