Biomarker | Median (Q1, Q3) at baseline | Reference range† | Time points assessed | ||
Placebo +csDMARDs (n=97)* | Sarilumab 150 mg q2w+csDMARDs (n=97)* | Sarilumab 200 mg q2w+csDMARDs (n=97)* | |||
Acute-phase response | |||||
CRP, mg/L | 15.9 (8.4–30.0) | 16.8 (9.9–30.5) | 22.8 (10.3–44.5) | ≤2.87 | BL, wks 2, 4, 8, 12, 16, 20 and 24 |
Myeloid activation | |||||
sICAM-1, ng/mL | 279.5 (249.2–346.0) | 297.9 (260.7–347.7) | 293.0 (253.9–354.3) | 186.7–315.0 | BL, wk 2 |
MRP8/14, μg/mL | 4.75 (2.8–8.9) | 5.88 (2.9–8.2) | 5.8 (3.2–10.3) | 1.755–12.77 | BL |
IL-8, pg/mL | 17.5 (10.8–31.6) | 22.0 (13.7–35.8) | 19.7 (12.3–31.7) | 2.84–16.5‡ | BL |
Lymphoid activation | |||||
CXCL13, pg/mL | 122.3 (90.4–176.3) | 129.3 (97.7–189.6) | 152.9 (110.6–224.3)§ | 28.58–89.28 | BL, wk 2, wk 24 |
CXCL10, pg/mL | 261.9 (183.6–417.7) | 302.4 (193.3–535.4) | 344.3 (221.7–505.2) | 69.86–383.0 | BL |
BAFF, pg/mL | 1142.2 (880.9–1506.2) | 1026.4 (854.0–1275.8) | 1064.1 (882.8–1415.9) | 762.2–1213.0 | BL, wk 24 |
Synovial inflammation | |||||
MMP-3, ng/mL | 46.9 (19.4–76.4) | 41.7 (26.1–79.5) | 60.4 (27.1–97.5)§ | 6.0–15.8 | BL, wk 2, wk 24 |
C1M, ng/mL | 81.8 (55.0–130.7) | 77.7 (59.2–121.2) | 88.6 (60.9–129.5)§ | 21.23–50.44 | BL, wk 2, wk 24 |
C3M, ng/mL | 19.8 (14.4–24.4) | 18.9 (15.0–23.0) | 20.8 (15.6–25.6) | 8.20–15.58 | BL, wk 2, wk 24 |
Bone remodelling | |||||
Total RANKL, pmol/L | 689.6 (340.9–1745.0) | 1033.6 (420.1–3296.4) | 1282.7 (386.1–3535.0)§ | 35.07–639.7 | BL, wk 12, wk 24 |
Free RANKL, pmol/L | 0.1 (0.1–0.2) | 0.2 (0.1–0.2) | 0.1 (0.1–0.2) | 0.03–0.266 | BL, wk 12, wk 24 |
OPG, pmol/L | 5.8 (4.7–7.4) | 5.4 (4.3–6.6) | 5.3 (4.1–7.3) | 3.552–7.920 | BL, wk 12, wk 24 |
OC, ng/mL | 16.8 (11.9–23.3) | 17.0 (11.6–23.0) | 19.4 (13.8–24.9) | 13.91–30.55 | BL, wk 24 |
*Patient numbers reflect maximum number of patients included in each group. Fewer samples may have been analysed at a given time point because of missing or non-evaluable samples.
†Reference range for postmenopausal women (5th–95th percentile) provided by Bioclinica Lab, Lyon, France; CRP reference range for healthy males and females provided by Covance Laboratories.
‡IL-8 reference range for healthy males and females provided by manufacturer R&D Systems.
§P value of the Kruskal-Wallis test (comparison of the values at baseline between treatment groups) <0.05.
BAFF, B cell-activating factor; BL, baseline; C1M, collagen type I MMP-cleaved fragment; C3M, collagen type III MMP-cleaved fragment; CRP, C-reactive protein; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; CXCL, chemokine, CXC motif, ligand; IL, interleukin; MMP, matrix metalloproteinase; MRP, myeloid-related protein; OC, osteocalcin; OPG, osteoprotegerin; q2w, every 2 weeks; RANKL, receptor activator of nuclear factor-κB ligand; sICAM-1, soluble intercellular adhesion molecule 1; wk, week.