POS0908 EFFICACY OF IXEKIZUMAB THROUGH 52 WEEKS FOR IMPROVING PERIPHERAL JOINT INVOLVEMENT AMONG PATIENTS WITH RADIOGRAPHIC-AXIAL SPONDYLOARTHRITIS
Authors: M. Magrey, K. De Vlam, A. Kronbergs, R. Bolce, D. Sandoval, X. Li, S. Liu Leage, D. Poddubnyy
Journal: Annals of the Rheumatic Diseases (2021)

Background: Radiographic-axial spondyloarthritis (r-axSpA) is a progressive chronic inflammatory disease primarily affecting the spine and sacroiliac joints. However, about 30-40% of patients (pts) with axSpA can have peripheral joint involvement, including joint tenderness and swelling, which can contribute significantly to burden of disease. Ixekizumab (IXE), a monoclonal antibody that neutralizes the pro-inflammatory cytokine interleukin-17A, has demonstrated a high level of efficacy in the treatment of r-axSpA. Objectives: The aim of this study is to evaluate the efficacy of IXE through 52 weeks (wks) in improving peripheral joint pain and swelling for pts with r-axSpA. Methods: Data was derived from two phase III randomised, double-blind, placebo (PBO)-controlled trials: one in pts with r-axSpA, who were biological disease-modifying anti-rheumatic drug (bDMARD)-naïve (COAST-V: NCT02696785 ), and the other in pts who were tumor necrosis factor inhibitor-experienced (COAST-W: NCT02696798 ). All pts had a confirmed diagnosis of r-axSpA and had to meet ASAS (Assessment of SpondyloArthritis international Society) criteria. IXE (80 mg) or PBO were administered subcutaneously every 2 (Q2W) or 4 (Q4W) wks during a 52-wk treatment period, after receiving a starting dose of 80 mg or 160 mg at wk 0. COAST-V/W pts originally randomised to PBO were re-randomised 1:1 to IXE Q4W or Q2W at wk 16. We present a post-hoc analysis of data from an integrated dataset from COAST-V and W (COAST-V/W); with intent to treat (ITT) pts categorized by baseline (BL) peripheral joint status. The presence of peripheral joint involvement was defined using a 46-joint tender joint count (TJC) &gt;0 or 44-joint swollen joint count (SJC) &gt;0. Treatment response through wk 52 was evaluated based on % improvement (20%, 50% or 70%) and resolution of tender or swollen joints of pts with BL TJC&gt;0 or SJC&gt;0, respectively. Missing data were imputed by non-responder imputation (NRI). Treatment comparison vs PBO at wk 16 was performed using Cochran-Mantel-Haenszel test. Results: This analysis includes 359 pts (63.4% of ITT) with baseline TJC&gt;0 and 203 pts (35.9% ITT) with baseline SJC&gt;0. The mean (SD) baseline TJC and SJC were 7.7 (8.3) and 4.3 (4.5), respectively. Mean BL TJC and SJC values by treatment group are presented in Table 1. A significant improvement of SJC by 20% and 50% was seen in pts treated with IXE Q4W compared to PBO at wk 16. Pts treated with IXE resulted in a numerically higher improvement in TJC and SJC symptoms up to wk 16 compared to PBO, and efficacy was sustained up to wk 52 (Table 1). A higher proportion of IXE-treated pts achieved high-hurdle efficacy endpoints (50% and 70% improvements) in comparison to PBO at wk 16 (Table 1). Over this time period, IXE treatment led to a high proportion of pts experiencing complete resolution of TJC or SJC vs PBO at wk 16, which was sustained up to wk 52 (Fig 1). Conclusion: In this post hoc analysis, pts with r-axSpA treated with IXE showed substantial improvement in peripheral joint pain and swelling. Table 1. Improvement of Tender or Swollen Joint Counts for pts with radiographic-axSpA with TJC&gt;0 or SJC&gt;0 at baseline (COAST-V/W) a - NRI Results % Improvement Radiographic-AxSpA Wk 16 52 b PBO IXE Q4W IXE Q2W IXE Q4W IXE Q2W N (TJC&gt;0 ) 116 129 114 129 114 BL TJC mean (SD ) 7.4 (8.8 ) 8.4 (8.4 ) 7.3 (7.5 ) %TJC improvement 20% 66.4 75.2 71.1 68.2 72.8 50% 52.6 61.2 64.9* 65.1 67.5 70% 37.9 47.3 50 55.8 54.4 N (SJC&gt;0 ) 67 72 64 72 64 BL SJC mean (SD ) 3.8 (4.6 ) 5.2 (5.2 ) 3.8 (3.3 ) %SJC improvement 20% 64.2 83.3 * 76.6 77.8 78.1 50% 56.7 77.8 † 70.3 75 76.6 70% 46.3 62.5 60.9 69.4 71.9 Abbreviations: COAST-V/W= integrated COAST-V and COAST-W; PBO = placebo; IXE= ixekizumab; Q4W = 80 mg IXE every 4 wks; Q2W = 80 mg IXE every 2 wks a Improvement in the number of tender or swollen joints were summarized on ITT patients who had tender (TJC&gt;0) or swollen (SJC&gt;0) joints at baseline, respectively b COAST-V/W PBO data are not available at wk 52 as pts originally randomised to PBO were re-randomised 1:1 to IXE Q4W or IXE Q2W at wk 16p-value vs. PBO at wk 16: *P&lt;0.05, †P&lt;0.01, ‡P&lt;0.001 Acknowledgements: Writing support was provided by Sinéad O’ Loughlin, an employee of Eli Lilly and Company Disclosure of Interests: Marina Magrey Consultant of: Novartis, UCB, Pfizer, Eli Lilly, Abbvie, Janssen, Kurt de Vlam Speakers bureau: UCB, Novartis, Pfizer, Eli Lilly, Amgen, Celgene, Paid instructor for: UCB, Amgen, Celgene, Consultant of: UCB, Novartis, Pfizer, Eli Lilly, Amgen, Celgene, Grant/research support from: Pfizer, Amgen, Celgene, Andris Kronbergs 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, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Xiaoqi Li Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, and Pfizer