Elevated levels of inflammatory cytokines such as TNF-α, IL-1, and IL-6 not only mediate joint destruction but also directly contribute to skeletal muscle atrophy through systemic circulation.58 These cytokines activate the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathways, promoting proteolysis while concurrently inhibiting anabolic pathways critical for muscle protein synthesis.48,49 Furthermore, RA-associated joint pain and functional limitations reduce physical activity and mechanical loading on muscles, exacerbating disuse-induced muscle atrophy. This evidence concerns the gene IL1B and rheumatoid arthritis.