POS0908 EFFICACY OF IXEKIZUMAB THROUGH 52 WEEKS FOR IMPROVING PERIPHERAL JOINT INVOLVEMENT AMONG PATIENTS WITH RADIOGRAPHIC-AXIAL SPONDYLOARTHRITIS
Authors: Magrey M. , De Vlam K. , Kronbergs A. , Bolce R. , Sandoval D. , Li X. , Liu Leage S. , Poddubnyy D. 
Published: May 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) >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.

Results:

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).

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>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%46.362.560.969.471.9

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

aImprovement 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, respectively

bCOAST-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<0.001

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