FRI0398 IXEKIZUMAB IS EFFECTIVE IN THE TREATMENT OF RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS REGARDLESS OF THE LEVEL OF C-REACTIVE PROTEIN OR MAGNETIC RESONANCE IMAGING SCORES: 16-WEEK DATA FROM COAST-V AND COAST-W

Abstract

Background Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease of the axial skeleton, and interleukin (IL)-17 plays an important role in the pathogenesis. Elevated C-reactive protein (CRP) levels in serum predict response to tumor necrosis factor inhibitors (TNFi)1-4 but not to secukinumab.5 The role of baseline spine magnetic resonance imaging (MRI) as a predictor of response has not been investigated for IL-17 inhibitors. Objectives To evaluate response rates at week (wk) 16 with ixekizumab (IXE), an IL-17A antagonist, in patients with ankylosing spondylitis (AS)/r-axSpA and elevated or normal/low inflammation as measured by CRP or spinal MRI. Methods Two Phase 3, randomized, double-blind, placebo (PBO)-controlled trials (COAST-V, NCT02696785; COAST-W, NCT02696798) enrolled patients who were biologic-naive or TNFi-experienced, respectively, with active disease (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥4 and spinal pain ≥4 on a numeric rating scale) and an established diagnosis of r-axSpA and fulfilling Assessment of SpondyloArthritis international Society (ASAS) criteria (sacroiliitis on radiograph by modified New York [mNY] criteria and ≥1 spondyloarthritis feature). All patients fulfilling ASAS criteria also fulfilled mNY criteria for AS. Patients were treated with IXE (80 mg every 2 or 4 wks [Q2W, Q4W]) or PBO; adalimumab (40 mg Q2W) was an active reference arm in COAST-V. We examined ASAS 40% (ASAS40) response rates at wk 16 for the intent-to-treat population by CRP (≤5 or >5 mg/L) or MRI spine inflammation (Spondyloarthritis Research Consortium of Canada [SPARCC] spine score, Results In the COAST-V/W integrated dataset that combined biologic-naive and TNFi-experienced populations, significantly more patients treated with IXE achieved ASAS40 response at wk 16 than with PBO in the elevated (>5 mg/L) baseline CRP group (39.3%, 42.5%, and 16.7% for IXE Q4W, IXE Q2W and PBO, respectively; p Conclusion IXE demonstrated rapid efficacy in the treatment of AS/r-axSpA at wk 16 irrespective of baseline serum CRP levels or spinal MRI score.