Effects of baricitinib on multibiomarker disease activity scores and their components in a phase 2B study in moderate-to-severe rheumatoid arthritis patients

Background and objectives Baricitinib, an oral inhibitor of JAK1 and JAK2 signalling, improved signs and symptoms in patients with active rheumatoid arthritis (RA) who were methotrexate inadequate responders (MTX-IR) in a double-blind, placebo (PBO) controlled study. We investigated how a quantitative, multibiomarker disease activity score (MBDA) and its components are affected by treatment with baricitinib 4mg (n = 50) once daily compared to PBO (n = 79) during 12 weeks' treatment in moderate-to-severe RA patients. Materials and methods Serum samples were collected at baseline and Weeks 4 and 12. MBDA scores and changes in individual MBDA components were subjected to post-hoc statistical analyses. Results At baseline, the proportion of patients with low, moderate, and high MBDA scores were similar in the 2 groups, as were median MBDA scores (PBO=44 vs. baricitinib=47). Unlike PBO-treated patients, baricitinib patients had decreased MBDA scores at 4 and 12 weeks compared to baseline (baricitinib=35.5 and 37.0 (p < 0.001) vs. PBO=46.0 and 45.0, respectively). Baricitinib- treated patients had significant (p < 0.05) median % decreases in MBDA components vs. PBO including C-Reactive Protein (- 66.9 vs. 6.6/-56.1 vs. 8.2 at 4/12 weeks), Matrix metalloproteinase (MMP)-3 (-12.3 vs. 4.5/-14.5 vs. 6.3 at 4/12 weeks), serum amyloid A (-56.4 vs. 9.9/-37.6 vs. 9.2 at 4/12 weeks), soluble TNF receptor (-12.1 vs. -0.1/-12.0 vs. 1.2 at 4/12 weeks), VCAM-1 (- 15.9 vs. 1.4/-12.1 vs. 1.0 at 4/12 weeks), and human cartilage glycoprotein 39; -26.2 vs. -0.5/-9.9 vs. -1.6 at 4/12 weeks). Compared to PBO, there were no significant changes for baricitinib-treated patients at either time-point for epidermal growth factor (EGF), MMP-1, or vascular endothelial growth factor-A. For baricitinib- treated patients versus PBO, at 4 but not 12 weeks, Interleukin-6 and resistin were significantly decreased and at 12 but not 4 weeks, leptin was significantly increased. Conclusions Consistent with other indices of disease activity, the treatment of MTX-IR patients with baricitinib 4mg once daily resulted in a reduction in MBDA scores, by 4 weeks. Decreases in MBDA scores and the components were present at both 4 and 12 weeks. Reduction in the levels of inflammatory markers beyond those associated with an acute phase response is apparent in these patients.