Skeletal effects of JAK1/2 inhibition versus IL-6 receptor blockade in rheumatoid arthritis: a post hoc comparative cohort analysis based on two prospective observational studies

Abstract

Introduction: Janus kinase inhibitors (JAKi) are increasingly used in rheumatoid arthritis (RA), yet comparative data on systemic effects beyond joint inflammation remain limited. Because chronic inflammation promotes generalized bone loss and IL-6-driven osteoclastogenesis, we compared the skeletal effects of baricitinib and tocilizumab over 12 months.

Methods: We performed an exploratory post hoc comparative cohort analysis based on two prospective single-center observational cohorts with harmonized eligibility criteria and identical endpoints. Patients with active RA initiating either baricitinib (n = 26) or tocilizumab (n = 22) underwent dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months. Primary outcomes were changes in bone mineral density (BMD) at the lumbar spine and femoral neck. Secondary analyses included changes in disease activity (DAS28-CRP) and multivariable models to identify factors associated with BMD change.

Results: No significant differences in BMD changes were observed between groups. Mean spine BMD increased by +8.2 mg/cm2 (+0.7%, 95% CI [−12.5.29.0]) with baricitinib and +15.6 mg/cm2 (+1.5%, 95% CI [−24.0.55.0]) with tocilizumab. Femoral BMD remained stable under baricitinib (+7.6 mg/cm2, +0.9%, 95% CI [−11.6.26.8]) but declined non-significantly with tocilizumab (−9.8 mg/cm2, -1.0%, 95% CI [−24.8.5.1]). Multivariable ANCOVA identified change in DAS28-CRP as the only factor significantly associated with spine BMD change (β = −0.36; p = 0.027). Treatment type, glucocorticoid exposure, and autoantibody status were not independently associated with BMD outcomes.

Conclusion: JAK1/2 inhibition with baricitinib and IL-6 receptor blockade with tocilizumab showed comparable 12-month effects on lumbar spine and femoral neck BMD. These findings suggest that preservation of bone health in RA is more closely linked to effective suppression of inflammatory activity than to a detectable advantage of one targeted mechanism over the other.