A Hypothetical Dual Pathway Therapeutic Strategy for Managing Rheumatoid Arthritis Associated Sarcopenia

Abstract

Rheumatoid arthritis is a chronic autoimmune disease that affects many tissues in the body. The disease mainly targets the joints, but its systemic effects are often ignored (Babaahmadi et al., 2023). One overlooked complication is rheumatoid arthritis associated sarcopenia. Sarcopenia in these patients begins early and progresses steadily. It reduces muscle mass and limits physical activity. Many patients describe this weakness as more disabling than joint pain. This condition deserves more attention in clinical practice (Bennett et al., 2023). Sarcopenia in rheumatoid arthritis is driven by chronic inflammation. Cytokines such as TNF-α, IL-6, and IL-1β remain elevated in most patients. These cytokines activate muscle catabolic pathways. NF-κB and JAK-STAT signaling increase protein degradation (Ding et al., 2025; Lozada-Mellado et al., 2024). Muscle repair becomes slow and inefficient. Reduced physical activity worsens this imbalance. Pain, fatigue, and stiffness prevent regular movement. This cycle accelerates muscle loss. Current rheumatoid arthritis therapies mainly target joint inflammation. Disease-Modifying Antirheumatic Drugs and biologics reduce inflammatory signals. They help control pain and joint swelling. However, they do not fully protect muscle tissue. Muscle wasting continues even when joint disease improves. Many patients show persistent functional impairment. This gap in therapy highlights an unmet need.