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The molecular targeted therapies available for rheumatoid arthritis include 10 types of biological disease-modifying antirheumatic drugs (bDMARDs) and five types of Janus kinase (JAK) inhibitors. This article reviews the differential and proper use of bDMARDs and JAK inhibitors, focusing on their efficacy and safety, based mainly on phase III clinical trials. The JAK inhibitors approved for treating rheumatoid arthritis are compared with bDMARDs based on the evidence derived from global phase III trials. In patients with inadequate responses to bDMARDs and JAK inhibitors, switching between these drugs is comparable in efficacy in both directions. Head-to-head comparison demonstrated that baricitinib and upadacitinib are more efficacious than tumor necrosis factor (TNF) inhibitors. However, the ORAL Surveillance study demonstrated that JAK inhibitors are associated with higher incidences of death, major adverse cardiovascular events, malignancies and thrombosis than TNF inhibitors in at-risk patients. The need for risk assessment by pre-treatment screening, regular monitoring during treatment, and appropriate systemic management in adverse events should be recognized. Meanwhile, some JAK-inhibitors were efficacious even for difficult-to-treat disease. These results suggest the need for establishing therapeutic strategies considering the balance between safety and efficacy in individual patients.

Making a prescribing choice for rheumatoid arthritis: a focus on small molecule drugs vs. biologics for the most favourable patient outcome