Modern Pharmacologic Management of Rheumatoid Arthritis: From Methotrexate to Targeted Therapies

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune pathology characterized by symmetric synovitis, pannus formation, and the potential for severe extra-articular manifestations. Despite historical associations with high morbidity, the 'treat-to-target' strategy has revolutionized patient outcomes. This review analyzes the pharmacological evolution of RA management over the last decade. We examine the foundational role of Methotrexate (MTX)—specifically its adenosine-mediated mechanism—and the stratification of biologic disease-modifying antirheumatic drugs (b-DMARDs), including TNF inhibitors, IL-6 receptor antagonists, and B-cell depleting agents. Crucially, we discuss the recent paradigm shift in the use of Janus Kinase (JAK) inhibitors following the 2021 ACR Guidelines and emerging safety data regarding cardiovascular and malignancy risks (the ORAL Surveillance trial). Finally, we explore the horizon of RA treatment, including GM-CSF inhibition, the complex management of difficult-to-treat (D2T) phenotypes, and the increasing integration of biosimilars to improve global treatment access.