The Janus kinase 1/2 inhibitor baricitinib reduces biomarkers of joint destruction in moderate to severe rheumatoid arthritis

• Published in: Arthritis research & therapy 2020-10, Vol.22 (1), p.235-11, Article 235
• Main Authors: Thudium, Christian S, Bay-Jensen, Anne C, Cahya, Suntara, Dow, Ernst R, Karsdal, Morten A, Koch, Alisa E, Zhang, Wenling, Benschop, Robert J
• Format: Article
• Language: English
• Subjects: Analysis; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Rheumatoid - drug therapy; Azetidines; Baricitinib; Biological markers; Biomarkers; Cartilage; Collagen; Connective tissue; Correlation analysis; Cytokines; Enzymes; Humans; Inflammation; Janus Kinase 1; Kinases; Laboratories; Medical research; Methotrexate - therapeutic use; Mutual fund industry; Peptides; Purines; Pyrazoles; Rheumatoid arthritis; Rheumatoid factor; Sulfonamides; Tumor necrosis factor-TNF
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-020-02340-7

Tissue released blood-based biomarkers can provide insight into drug mode of action and response. To understand the changes in extracellular matrix turnover, we analyzed biomarkers associated with joint tissue turnover from a phase 3, randomized, placebo-controlled study of baricitinib in patients with active rheumatoid arthritis (RA). Serum biomarkers associated with synovial inflammation (C1M, C3M, and C4M), cartilage degradation (C2M), bone resorption (CTX-I), and bone formation (osteocalcin) were analyzed at baseline, and weeks 4 and 12, from a subgroup of patients (n = 240) randomized to placebo or 2-mg or 4-mg baricitinib (RA-BUILD, NCT01721057). Mixed-model repeated measure was used to identify biomarkers altered by baricitinib. The relationship between changes in biomarkers and clinical measures was evaluated using correlation analysis. Treatment arms were well balanced for baseline biomarkers, demographics, and disease activity. At week 4, baricitinib 4-mg significantly reduced C1M from baseline by 21% compared to placebo (p