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
Authors: Walter P. Maksymowych, Gaia Gallo, Rebecca Bolce, Fangyi Zhao, Vladimir Geneus, Mikkel Ǿstergaard, Kurisu Tada, Atul Deodhar, Lianne S. Gensler
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> 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)<sup>1-4</sup> but not to secukinumab.<sup>5</sup> The role of baseline spine magnetic resonance imaging (MRI) as a predictor of response has not been investigated for IL-17 inhibitors. <h3>Objectives</h3> 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. <h3>Methods</h3> 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 &gt;5 mg/L) or MRI spine inflammation (Spondyloarthritis Research Consortium of Canada [SPARCC] spine score, &lt;2 or ≥2). Baseline spine MRI was available in 96% of patients in COAST-V and 51% of patients in COAST-W; scoring was done by central readers. Higher scores reflect greater baseline disease activity. Sacroiliac joint MRIs were not assessed. Missing data for ASAS40 were imputed by nonresponder imputation. <h3>Results</h3> 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 (&gt;5 mg/L) baseline CRP group (39.3%, 42.5%, and 16.7% for IXE Q4W, IXE Q2W and PBO, respectively; p&lt;.001 for IXE Q4W, IXE Q2W vs PBO) and in the normal (≤5 mg/L) baseline CRP group (27.4%, 35.2%, and 12.3% for IXE Q4W, IXE Q2W and PBO, respectively; p&lt;.05 for IXE Q4W, p&lt;.01 for IXE Q2W vs PBO, Fig 1), and the magnitude of response with IXE between elevated vs normal CRP groups was not statistically significant. Notably, a significantly higher proportion of patients achieved ASAS40 at wk 16 with IXE than with PBO, regardless of whether MRI spine SPARCC scores were &lt;2 (40%, 51.7%, and 15.5% for IXE Q4W, IXE Q2W and PBO, respectively; p&lt;.01 for IXE Q4W, p&lt;.001 for IXE Q2W vs PBO) or ≥2 (44.3%, 46.6%, and 18.7% for IXE Q4W, IXE Q2W and PBO, respectively; p&lt;.001 for IXE Q4W, IXE Q2W vs PBO, Fig 1). <h3>Conclusion</h3> IXE demonstrated rapid efficacy in the treatment of AS/r-axSpA at wk 16 irrespective of baseline serum CRP levels or spinal MRI score. <h3>References</h3> [1] Inman, et al. 2008 [2] Braun, et al. 2016 [3] de Vries, et al. 2009 [4] Vastesaeger, et al. 2011 [5] Braun, et al. 2018 <h3>Disclosure of Interests</h3> Walter P. Maksymowych Grant/research support from: Abbvie, Pfizer, Novartis, Consultant for: Abbvie, Boehringer, Celgene, Lilly, Novartis, Pfizer, UCB, Speakers bureau: Honoraria from Abbvie, Boehringer, Celgene, Lilly, Novartis, Pfizer, UCB for speaking events but I am not in any speaker's bureau., Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Fangyi Zhao Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Vladimir Geneus Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Kurisu Tada Grant/research support from: Eli Lilly, Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Lianne S. Gensler Grant/research support from: Abbvie, Amgen, UCB Pharma , Consultant for: Novartis, Lilly, Janssen