P281 52-Week efficacy and safety of ixekizumab in r-axSpA/AS patients naïve to biologic treatments or with prior inadequate response/intolerance to tumor necrosis factor inhibitors

Abstract

Abstract Background Radiographic axial spondylitis (r-axSpA), or ankylosing spondylitis (AS), is a chronic inflammatory disease of the axial skeleton associated with serious pain, stiffness and limited flexibility, impairing quality of life. Two clinical trials demonstrated efficacy and safety of ixekizumab (IXE), a humanised anti-IL-17 IgG4 antibody, in r-axSpA/AS patients naïve to biologics, or with prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi) over 16 weeks. This study assessed the treatment effect over 52 weeks. Additionally, the influence of baseline inflammation, measured by C-reactive protein (CRP) and/or spinal MRI on ASAS40 response at week 16 was investigated. Methods Data from two Phase 3, randomised, double-blind, placebo (PBO)-controlled trials, with patients who fulfilled the Assessment of Spondylo-Arthritis International Society (ASAS) criteria for AS and were either biologic-naïve (COAST-V, NCT02696785) or TNFi-experienced (COAST-W, NCT02696798), were analysed. We compared the proportion of patients achieving ASAS20/40, a 50% improvement of baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) and assessed the change in spinal pain. Missing data was handled by using non-responder imputation for ASAS20/40 and BASDAI50 response rates and modified Baseline Observation Carried Forward (mBOCF) for spinal pain change from baseline. To investigate the influence of baseline inflammation on the efficacy, we examined the ASAS40 response at week 16 by baseline CRP (normal; ≤5 or elevated; >5 mg/L) and/or MRI Spondyloarthritis Research Consortium of Canada (SPARCC) spine score (<2 or ≥ 2) using an integrated COAST-V/W dataset. Results At week 16, significantly more IXE than PBO-treated patients achieved ASAS20/40 and BASDAI50 and a decrease in spinal pain. Decreases in disease activity were maintained through week 52 (Table 1). These outcomes occurred in both biologic-naïve and TNFi-experienced patients. Safety outcomes were consistent with previous IXE studies. At week 16, in the integrated dataset, significantly more IXE than PBO-treated patients achieved ASAS40 response regardless of baseline CRP or MRI spine SPARCC score. Conclusion Through week 52, treatment with IXE resulted in sustained efficacy in biologic-naïve and TNFi-experienced AS patients with no unexpected safety signals. Furthermore, at week 16, IXE demonstrated efficacy (ASAS40) irrespective of baseline CRP levels or spinal MRI score. Disclosures K. Gaffney: Consultancies; Abbvie, Eli Lilly, UCB, Novartis. Member of speakers’ bureau; Eli Lilly, UCB, Novartis. Grants/research support; Abbvie, Pfizer. D. Aletaha: Member of speakers’ bureau; Abbvie, Amgen, Celgene, Eli Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sanofi/Genzyme. Grants/research support; Abbvie, Novartis, Roche. A.J. Bradley: Corporate appointments; Eli Lilly employee. Shareholder/stock ownership; Eli Lilly. M.H. Nassab: Corporate appointments; Eli Lilly employee. S. Liu Leage: Corporate appointments; Eli Lilly employee. R. Micheroli: None.