Session Information
Date: Sunday, October 21, 2018
Title: Rheumatoid Arthritis – Treatments Poster I: Strategy and Epidemiology
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with outcomes in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ); levels of matrix metalloproteinase-3 (MMP-3) and S100A8/A9 have also been associated with disease activity and joint damage. This study evaluated 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 – erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 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. Spearman correlations between CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels and DAS28-ESR at baseline, Week 24 and Week 40 were analyzed. 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 biomarker levels were observed from baseline to Week 24 (open-label period) in all 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.
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Table. Changes in Serum Biomarker Levels from Week 24 to Week 40 (Randomized Period) in Patients Receiving TCZ as Monotherapy or in Combination With MTX |
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Estimated Mean Change From Week 24 to 40* (95% CI) |
TCZ Mono (n = 126) |
TCZ + MTX (n = 123) |
Difference, TCZ Mono Minus TCZ + MTX (95% CI) |
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CXCL13 (pg/mL) |
−0.02 (−0.05 to 0.01) |
−0.04 (−0.07 to −0.00) |
0.02 (−0.02 to 0.05) |
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sICAM-1 (pg/mL) |
0.01 (−0.01 to 0.02) |
−0.01 (−0.03 to 0.01) |
0.01 (−0.01 to 0.03) |
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MMP-3 (ng/mL) |
0.04 (0.01 to 0.08) |
0.03 (−0.00 to 0.07) |
0.01 (−0.03 to 0.05) |
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S100A8/A9 (ng/mL) |
0.01 (−0.05 to 0.07) |
−0.05 (−0.12 to 0.01) |
0.06 (−0.01 to 0.13) |
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ANCOVA, analysis of covariance; CXCL13, C-X-C motif chemokine ligand 13; DAS28-ESR, Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate; MMP-3, matrix metalloproteinase-3; mono, monotherapy; MTX, methotrexate; q2w, every 2 weeks; qw, once a week; sICAM-1, soluble intercellular adhesion molecule-1; TCZ, tocilizumab; TNFi, tumor necrosis factor inhibitor. * ANCOVA model for estimated mean included log10 transformed Week 24 biomarker value as a covariate, treatment group and the following randomization stratification factors: DAS28-ESR remission status at Week 24 (< 2.6, ≥ 2.6 to ≤ 3.2), patient TNFi exposure (yes or no), baseline weight-by-dosing group (< 80 kg q2w, 80 to < 100 kg q2w, 80-to < 100 kg qw, ≥ 100 kg qw). |
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To cite this abstract in AMA style:
Haddon DJ, Sornasse T, Townsend MJ, Pei J, Michalska M. Evaluation of CXCL13, sICAM1, MMP-3 and S100A8/A9 As Serum Biomarkers in Patients with Rheumatoid Arthritis Treated with Subcutaneous Tocilizumab [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/evaluation-of-cxcl13-sicam1-mmp-3-and-s100a8-a9-as-serum-biomarkers-in-patients-with-rheumatoid-arthritis-treated-with-subcutaneous-tocilizumab/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-cxcl13-sicam1-mmp-3-and-s100a8-a9-as-serum-biomarkers-in-patients-with-rheumatoid-arthritis-treated-with-subcutaneous-tocilizumab/