New frontiers in rheumatoid arthritis therapy: From classic DMARDs to biologics and beyond

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder identified by persistent synovial inflammation, joint destruction, and systemic complications. Affecting approximately 0.5-1 % of the global population, RA poses a considerable burden in terms of disability and healthcare costs. Over the past century, insights into RA pathogenesis-driven by immune dysregulation, genetic predisposition, and environmental triggers-have revolutionized therapeutic strategies. This review provides a detailed overview of the evolving landscape of RA drug development, tracing the progression from conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate and sulfasalazine, to targeted synthetic DMARDs (tsDMARDs) like JAK inhibitors, and biologic DMARDs (bDMARDs) including TNF and IL-6 antagonists. We explore the molecular underpinnings of RA, discuss the mechanisms of action and clinical applications of current therapies, and highlight emerging drug candidates under clinical investigation. Despite significant advances, challenges such as incomplete remission rates, variable patient responses, and long-term safety concerns underscore the need for precision medicine and novel therapeutic approaches. This review emphasizes the critical role of immunopathology in guiding RA drug development and the ongoing efforts to achieve personalized, sustained disease control.