JAK Inhibitors for Rheumatoid Arthritis: Assessing Efficacy and Safety in Treatment

Abstract

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, progressive joint destruction, and systemic complications. Dysregulated cytokine signaling through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays a central role in RA pathogenesis, making JAK inhibitors an important therapeutic option. Tofacitinib, baricitinib, and upadacitinib are oral targeted synthetic disease-modifying antirheumatic drugs that interfere with cytokine signaling and reduce inflammatory activity. In randomized trials, these agents achieved American College of Rheumatology 20% improvement (ACR20) responses in approximately 60–75% of patients and demonstrated efficacy comparable to, and in some studies exceeding, that of adalimumab. Their oral administration and rapid onset of action represent practical advantages, particularly in patients with inadequate responses to conventional synthetic or biologic DMARDs. However, treatment is associated with important safety concerns, including serious infections, herpes zoster, venous thromboembolism, major adverse cardiovascular events, and malignancy. A personalized risk-benefit assessment and ongoing monitoring remain essential to optimize outcomes and ensure long-term safety.