#2-28E. Reassessing Creatinine: JAK Inhibition and Skeletal Muscle Hypertrophy in RA (LANCET RHEUMATOL, 2025)

Rheumatoid arthritis (RA) patients face an elevated risk of generalized muscle wasting, known as sarcopenia, which significantly complicates clinical management. A persistent clinical question has been how Janus kinase (JAK) inhibitors, which frequently cause modest elevations in serum creatinine without clear evidence of nephrotoxicity, truly impact muscle health. The RAMUS study, a single-arm, proof-of-concept trial, addressed this by investigating the skeletal muscle effects of six months of tofacitinib treatment in RA patients using quantitative MRI. The core finding reveals that tofacitinib treatment was associated with a significant increase in lower limb muscle volume (mean 4%), supporting the hypothesis that the concurrent increase in serum creatinine likely reflects this gain in muscle mass, not renal dysfunction. This suggests a potential anti-sarcopenic effect, possibly through transcriptional changes opposing the signature seen in age-related sarcopenia. Clinicians should note that these results provide crucial context for interpreting laboratory values during JAK inhibitor therapy and introduce the possibility that this drug class may offer an added benefit in mitigating RA-associated muscle loss. Nevertheless, the study’s limitation as a small, single-arm design (N=15) means causality cannot be definitively proven, mandating verification through larger randomized controlled trials.

Citation: Bennett JL, Hollingsworth KG, Pratt AG, et al. Skeletal muscle effects of Janus kinase inhibition in rheumatoid arthritis (RAMUS): a single-arm, experimental medicine study. Lancet Rheumatol. 2025. DOI: https://doi.org/10.1016/S2665-9913(25)00184-5114

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