Systematic review on tuberculosis risk in patients with rheumatoid arthritis receiving inhibitors of Janus Kinases

Janus kinases inhibitors (anti-JAKs), including tofacitinib, baricitinib, upadacitinib, and filgotinib, represent a new class of synthetic targeted drugs for the treatment of rheumatoid arthritis (RA). In this review, the risk of active tuberculosis (TB) occurrence in patients receiving anti-JAKs was assessed. The literature on this topic, updated to 29 February 2020 was reviewed. Overall, 40 reports (22 tofacitinib, 10 baricitinib, 5 upadacitinib, 3 filgotinib) were examined. A low frequency, not exceeding 0.25%, of active TB cases in patients were exposed to anti-JAKs. Only 1 of 89 recorded cases in tofactinib and baricitinib exposure occurred in countries at intermediate or high TB risk, and most of the cases probably were due to first mycobacterium tuberculosis (Mtb) exposure. Although no cases were observed in patients receiving upadacitinib and filgotinib, long-term trials and data from real-life are required to more precisely address the TB risk associated with the two drugs.Discussion on the TB risk associated with anti-JAKs, and on the need for accurate evaluation of host-related risk factors in high risk countries.Available data on anti-JAKs suggest a negligible risk of active TB occurrence in low endemic areas.