POS0908\u2005EFFICACY OF IXEKIZUMAB THROUGH 52 WEEKS FOR IMPROVING PERIPHERAL JOINT INVOLVEMENT AMONG PATIENTS WITH RADIOGRAPHIC-AXIAL SPONDYLOARTHRITIS

Abstract

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.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.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\u2009mg) 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\u2009mg or 160\u2009mg 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) >0 or 44-joint swollen joint count (SJC) >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>0 or SJC>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.This analysis includes 359 pts (63.4% of ITT) with baseline TJC>0 and 203 pts (35.9% ITT) with baseline SJC>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).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>0 or SJC>0 at baseline (COAST-V/W)a - NRI Results% ImprovementRadiographic-AxSpAWk1652bPBOIXE Q4WIXE Q2WIXE Q4WIXE Q2WN (TJC>0)116129114129114BL TJC mean (SD)7.4 (8.8)8.4 (8.4)7.3 (7.5)%TJC improvement20%66.475.271.168.272.850%52.661.264.9*65.167.570%37.947.35055.854.4N (SJC>0)6772647264BL SJC mean (SD)3.8 (4.6)5.2 (5.2)3.8 (3.3)%SJC improvement20%64.283.3*76.677.878.150%56.777.8†70.37576.670%46.362.560.969.471.9Abbreviations: COAST-V/W= integrated COAST-V and COAST-W; PBO = placebo; IXE= ixekizumab; Q4W = 80\u2009mg IXE every 4 wks; Q2W = 80\u2009mg IXE every 2 wksaImprovement in the number of tender or swollen joints were summarized on ITT patients who had tender (TJC>0) or swollen (SJC>0) joints at baseline, respectivelybCOAST-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<0.05, †P<0.01, ‡P<0.001Writing support was provided by Sinéad O’ Loughlin, an employee of Eli Lilly and CompanyMarina 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