Introduction: The Burden of Muscle Wasting in Rheumatoid Arthritis
nnRheumatoid arthritis (RA) is characterized not only by synovial inflammation and joint destruction but also by significant systemic metabolic consequences, most notably rheumatoid cachexia. This condition, defined by the loss of skeletal muscle mass (sarcopenia) in the presence of stable or increased fat mass, affects a substantial proportion of patients even when joint symptoms are clinically managed. Chronic systemic inflammation, driven by cytokines such as TNF-alpha, IL-6, and various interferons, accelerates muscle protein degradation and inhibits myogenic differentiation. Consequently, patients face reduced physical function, increased frailty, and a higher risk of metabolic comorbidities.nnJanus kinase (JAK) inhibitors, such as tofacitinib, have revolutionized RA management by targeting the signaling pathways of multiple pro-inflammatory cytokines. However, a consistent observation in clinical trials of tofacitinib has been a modest, non-progressive increase in serum creatinine levels. While this initially raised concerns regarding nephrotoxicity, subsequent analyses suggested no significant decline in glomerular filtration rate (GFR). The Rheumatoid Arthritis and Muscle (RAMUS) study was designed to investigate an alternative hypothesis: that this creatinine rise reflects an increase in muscle mass and volume rather than renal impairment.nn
