Efficacy of Ixekizumab in active psoriatic arthritis (PSA) patients with axial pain starting before age 45: A subgroup analysis of spirit-P1 and spirit-P2 phase 3 clinical trials

Background: The efficacy and safety of ixekizumab (IXE), an IL-17A antagonist, was investigated in patients with active psoriatic arthritis (PsA) in the SPIRIT-P1 and SPIRIT-P2 clinical trials. Objectives: To investigate the efficacy of ixekizumab on axial pain, fatigue, stiffness, and physical function in a subset of patients with PsA self-reporting axial pain starting before the age of 45 years at baseline. Methods: Patients with PsA in the intent-to-treat populations of SPIRIT-P1 (Biologic-naïve; NCT01695239) and SPIRIT-P2 (Inadequate responders or intolerant to 1 or 2 TNF inhibitors; NCT02349295) with baseline patientreported axial pain (≥4 Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] question 2), high-sensitivity C-reactive protein (hsCRP) >5mg/L, and <45 years old were included in this post-hoc integrated analysis. SPIRIT-P1/P2 did not include axial imaging. Patients were treated with placebo (PBO) or ixekizumab 80-mg every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) after a 160-mg starting dose for 24 weeks. The efficacy of ixekizumab on axial pain (BASDAI question 2), fatigue (BASDAI question 1), stiffness (mean of BASDAI questions 5/6), total BASDAI, Health Assessment Questionnaire Disability Index (HAQ-DI), and 36-Item Short Form Health Survey Physical Component Summary (SF-36 PCS) was analyzed at Weeks 16 and 24 using mixed model for repeated measures with treatment, region, baseline conventional DMARD experience, visit, and treatment-by-visit interaction as fixed factors, and response value at baseline as a covariate. Results: Axial pain and stiffness significantly improved at Weeks 16 and 24 in patients with PsA treated with IXEQ4W or IXEQ2W versus PBO (p<.05; Table 1). Fatigue significantly improved at Week 16 in patients treated with IXEQ4W or IXEQ2W versus PBO and at Week 24 with IXEQ2W versus PBO (p<.05). Total BASDAI scores significantly improved at Weeks 16 and 24 in patients treated with IXEQ4W or IXEQ2W versus PBO (p<.01). Physical function significantly improved at Weeks 16 and 24 in patients treated with IXEQ4W or IXEQ2W versus PBO when assessed by HAQ-DI or SF-36 PCS (p<.05). Conclusion: Ixekizumab treatment yielded significantly higher improvements than placebo in axial pain, fatigue, stiffness, and physical function at Weeks 16 and 24 in the integrated PsA subpopulation self-reporting axial pain at baseline. These analyses were limited by a lack of baseline axial imaging.