Recent issues in JAK inhibitor safety: perspective for the clinician.

INTRODUCTION: Five jakinibs are approved for the treatment of rheumatic diseases. There has been a question of their relative safety to other medications since their approval. AREAS COVERED: A literature search was conducted in Pub Med for the integrated safety databases of these molecules in their clinical trial program, registries, and insurance claims data and in a prospective head-to-head study compared to tumor necrosis factor inhibitors in a high-risk population for cardiovascular and malignancy events. There were no differences found in the safety databases, registries or insurance claims data indicating jakinibs are more likely to cause major adverse cardiac events, malignancy, venous thrombotic episodes, infections, and mortality compared to other medications. The head-to-head trial found that there were numerically more of these events with the jakinib compared to tumor necrosis factor inhibitors. EXPERT OPINION: Cardiac events and malignancy occur more frequently in rheumatoid patients with active disease. Although the safety databases, claims data, and registries suggest that there is no difference in the risks with a jakinib versus biologics, the prospective safety study showed these events occur numerically higher in patients at the highest risk for these events. In this population, one should consider using a biologic before a jakinib.