Introduction: The Burden of Rheumatoid Cachexia
Rheumatoid arthritis (RA) is traditionally characterized by synovial inflammation and joint destruction. However, the systemic nature of the disease frequently leads to significant extra-articular manifestations, most notably rheumatoid cachexia. This condition, defined by the loss of skeletal muscle mass (sarcopenia) often accompanied by stable or increased fat mass, affects approximately two-thirds of patients with RA. Unlike age-related sarcopenia, rheumatoid cachexia is driven by chronic systemic inflammation, where pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-1 beta accelerate protein degradation via the ubiquitin-proteasome pathway and inhibit muscle protein synthesis.
The clinical consequences of muscle wasting in RA are profound, contributing to physical disability, increased fatigue, reduced quality of life, and higher metabolic risk. While traditional disease-modifying antirheumatic drugs (DMARDs) and TNF inhibitors have shown some efficacy in slowing muscle loss, the restoration of muscle volume remains a significant unmet medical need. The Janus kinase (JAK) inhibitor tofacitinib has emerged as a potent therapy for RA, but its specific impact on skeletal muscle—beyond its anti-inflammatory effects—has remained largely unexplored until the RAMUS study.
