P277 Ixekizumab shows a distinct pattern of pain improvement beyond measurable inflammation as assessed by MRI, CRP or BASDAI questions 5 and 6 in patients with ankylosing spondylitis
Authors: Maney Nicola , de Vlam Kurt , Conaghan Philip G , Mease Philip J , Rahman Proton , Krishnan Venkatesh , Bolce Rebecca , Calderon David Marcelino Sandoval , Park So Young , Gallo Gaia , Maksymowych Walter 
Published: April 2022

Abstract

Background/Aims
Efficacy of ixekizumab (IXE) in patients (pts) with ankylosing spondylitis (AS) at week (W) 16 in the absence of elevated inflammation as measured by CRP and MRI Spondyloarthritis Research Consortium of Canada (SPARCC) has been previously reported. In this analysis, we evaluated the improvement in pain with IXE based on longitudinal status of objective measures of inflammation by MRI, CRP value, and BASDAI 5/6 over 16W.

Methods
The Phase III COAST-V (NCT02696785) 52W, multi-center, randomized, double-blind, placebo (PBO)-controlled study examined the efficacy of IXE in pts with active AS. Adalimumab (ADA) was used as an active reference arm for the first 16W. Pts assigned to ADA went through a wash-out period of 6W prior to getting their first dose of IXE. Change in spinal pain at night (SP-N) and Short Form 36 Health Survey Questionnaire (SF-36) Bodily Pain were measured during study visits and analyzed while controlling for inflammation status using MRI, CRP levels and mean of BASDAI 5/6 (Q5: Duration, Q6: Intensity of morning stiffness). Observed data analyses are presented for each group stratified by treatment arm. Initial analysis: ‘controlled inflammation’ is defined as MRI SPARCC SI joint &lt;4 and MRI SPARCC Spine &lt;3 at W16, CRP &lt;5mg/L at every visit W4-16, or BASDAI 5/6 improvement of ≥ 2 points W12 and W16. Second analysis: control is defined as CRP &lt;5 mg/L at every week between W4-16 and MRI SPARCC SI joint &lt;4 at W16 and MRI SPARCC Spine &lt;3 at W16.

Results
When inflammation is controlled per MRI, pts treated (tx) with IXEQ4W (-3.9 p&lt;0.001) and ADA (-2.8 p=0.02) experienced significant reduction in SP-N vs PBO (-1.6) at W16; further improvements were experienced in pts rerandomized to IXE by W52. When inflammation was not controlled per MRI, IXEQ4W (-3.5 p&lt;0.01) and ADA (-3.1 p=0.02) experienced significant reduction in SP-N at W16; all IXE tx pts had further reductions at W52. When inflammation was controlled per MRI+CRP, IXEQ4W (-3.8 p=0.2) and ADA (-3.1 p=0.4) had reduction in SP-N at W16 vs PBO (-2.4); all IXE groups had further improvements at W52. When inflammation was not controlled as measured by MRI+CRP, IXEQ4W (-3.7 p&lt;0.001) had significant reduction in SP-N vs PBO (-1.7), whereas improvement with ADA (-2.6 p=0.06) was not significant; all IXE tx pts had further reduction by W52. For SF-36 bodily pain, improvements were observed with IXE and ADA at W16 and W52, whether inflammation was controlled or not controlled per MRI, CRP, MRI+CRP, or BASDAI 5/6.

Conclusion
This analysis adds support to the hypothesis that IXE improves pain in pts with and without measurable inflammation.

Disclosure
N. Maney: None. K. de Vlam: Consultancies; Celgene, Eli Lilly and Company, Galapagos NV, Novartis, Pfizer, and UCB Pharma. Grants/research support; Celgene. P.G. Conaghan: Consultancies; Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Novartis, Pfizer, and UCB Pharma. P.J. Mease: Member of speakers’ bureau; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. P. Rahman: Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. V. Krishnan: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. D. Marcelino Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. S. Park: Shareholder/stock ownership; Eli Lilly and Company. G. Gallo: Shareholder/stock ownership; Eli Lilly and Company. W. Maksymowych: Grants/research support; AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Galapagos NV, Janssen, Novartis, Pfizer, and UCB Pharma; and is the Chief Medical Officer of CARE Arthritis Ltd.