AB0272\u2005EVALUATION OF CXCL13, SICAM-1, MMP-3 AND S100A8/A9 AS SERUM BIOMARKERS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH SUBCUTANEOUS TOCILIZUMAB

Abstract

Background Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to tocilizumab (TCZ) in patients with rheumatoid arthritis (RA); levels of matrix metalloproteinase-3 (MMP-3) and S100A8/A9 have also been associated with RA disease activity and joint damage. Objectives To evaluate the association of CXCL13, sICAM-1, MMP-3 and s100A8/A9 levels with disease activity and response to TCZ in patients with RA who achieved low disease activity with 24 weeks of TCZ + methotrexate (MTX) treatment and were subsequently randomized to TCZ monotherapy (mono) or TCZ + MTX in the COMP-ACT trial (NCT01855789). Methods US patients with RA who had an inadequate response to MTX received initial combination therapy of MTX plus TCZ 162 mg subcutaneous for 24 weeks. Patients who achieved Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to receive either TCZ mono or continue TCZ + MTX until Week 52. Randomized patients were included in the present study based on baseline, Week 24 and Week 40 sample availability; serum levels of CXCL13, sICAM-1, MMP-3 and S100A8/A9 were measured by immunoassay. Correlations between CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels and DAS28-ESR at baseline, Week 24 and Week 40 were determined according to Spearman correlation coefficient. Changes in CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels from baseline to Week 24 (open-label period) were determined using Wilcoxon test. Mean changes in CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels from Week 24 to Week 40 (randomized period) were compared between treatment arms using analysis of covariance. Results Of 296 randomized patients, 249 were included (TCZ mono, n = 126; TCZ + MTX, n = 123). Biomarker levels were well balanced across treatment arms at baseline and Week 24 (randomization). At baseline, there were weak to mild correlations between DAS28-ESR and biomarker levels (CXCL13 [r = 0.13, P = 0.0411], sICAM-1 [r = 0.20, P = 0.0015], MMP-3 [r = 0.19, P = 0.0021], S100A8/A9 [r = 0.25, P = 0.0001]). Significant reductions in mean biomarker levels were observed from baseline to Week 24 (open-label period) among the total randomized patients (P < 0.0001). CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels were relatively stable between Week 24 and Week 40 (randomized period), with no significant differences between TCZ mono and TCZ + MTX (Table). Conclusion In agreement with previous studies, the association between baseline disease activity and CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels was weak to mild; TCZ + MTX treatment from baseline to Week 24 (open-label period) resulted in significant reductions in all biomarkers. Changes in levels of CXCL13, sICAM-1, MMP-3 and S100A8/A9 from Week 24 to 40 (randomized period) were similar between treatment groups, consistent with the finding of non-inferiority of TCZ mono compared with TCZ + MTX in patients with RA who achieve low disease activity with TCZ + MTX. Acknowledgement This study was funded by Genentech, Inc. Disclosure of Interests D. James Haddon Shareholder of: Stockholder of Genentech/Roche, Employee of: Employee of Genentech/Roche, Thierry Sornasse Employee of: Genentech, Inc., Michael J. Townsend Shareholder of: Stockholder of Genentech/Roche, Employee of: Genentech/Roche, Jinglan Pei Employee of: Genentech, Margaret Michalska Employee of: Genentech, Inc.