JAK Inhibitors for Rheumatoid Arthritis

Abstract

Although biologic therapies have changed expectation and outcomes for rheumatoid arthritis, the optimal therapy for this disease has yet to be determined. There are still a significant number of patients who do not respond satisfactorily to currently available therapies. The Janus kinase inhibitors represent a new class of therapies for rheumatoid arthritis. Tofacitinib is the first drug in this class to have demonstrated efficacy and a reasonable safety profile, and other examples, such as baracitinib, are in the late stages of development. These drugs work uniquely by inhibiting intracellular pathways thought to be important in the pathogenesis of rheumatoid arthritis. They are available as oral agents, which is also different than the currently available biologics. Tofacitinib has been carefully evaluated in multiple phase 3 clinical trials, and although safety concerns cannot fully be answered until the drug is studied over longer periods of time, the data to date suggest that this drug—and perhaps other JAK inhibitors—may represent an important addition to the therapeutic armamentarium. Further study and experience will better define when these drugs should be used and in which patients. Janus kinase (JAK) inhibitors are a novel approach to the treatment of rheumatoid arthritis (RA). They specifically inhibit some of the intracellular mechanisms involved in the immune-pathogenesis of the disease. An example of a JAK inhibitor is tofacitinib, which has demonstrated efficacy in multiple clinical trials, with a safety profile not substantially different from the biologic agents currently available. Baracitinib has also demonstrated efficacy in phase 3 clinical trials which are to be published soon. Other JAK inhibitors are also currently being evaluated. Their mechanism of action and oral route of administration is unique compared to biologic therapies to date, and their place in the rheumatologist’s armamentarium has yet to be determined.