Effect of JAK Inhibitor on Bone Erosion Repair in Rheumatoid Arthritis (JAKE): Study Protocol of a Randomized Placebo-Controlled Study

Objective: To investigate the effect of Janus kinase (JAK) inhibition by baricitinib on erosion repair in rheumatoid arthritis (RA) patients with active disease using high-resolution peripheral quantitative computer tomography (HR-pQCT). Hypothesis: JAK inhibitor can lead to repair of existing erosion in RA patients with active disease. Design and Subjects: This is a 24-week, randomized, placebo-controlled, double-blind study. We plan to enroll 60 adult patients with active RA (disease activity score 28-C-reactive protein [DAS28-CRP] > 3.2) and at least one bone erosion on HR-pQCT. They will be randomized 1:1 to receive JAK inhibitor (baricitinib 4 mg once daily) or placebo for 24 weeks. Medications will be adjusted according to a standard protocol aiming to achieve low disease activity. Biologic or other targeted synthetic disease-modifying antirheumatic drugs are not permitted. Methodology: HR-pQCT of the 2-4 metacarpophalangeal joints will be done at baseline and 24 weeks. Inflammatory cytokine profile and bone–cartilage interface biomarkers will also be checked at baseline and 24 weeks. Clinical response will be monitored using DAS28-CRP. Main Outcome Measures and Analysis: The primary outcome is the proportion of patients with erosion volume regression on HR-pQCT, comparing the two groups by chi-square test. Secondary outcomes include dimensions of erosion, marginal osteosclerosis, and joint space width on HR-pQCT; RA disease activity; and serum biomarkers. The above-mentioned parameters will be compared before and after treatment by Wilcoxon signed-rank, with their changes compared between the two treatment arms using the Mann–Whitney [Formula: see text]test. Independent factors predicting response to JAK inhibitors will be analyzed by multivariate logistic regression.