Details
Tofacitinib, an oral Janus kinase (JAK) inhibitor, was approved in 2012 for the treatment of adult patients with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. The FDA issued a postmarket requirement (PMR) at the time of approval for RA for a controlled clinical trial to evaluate the long-term safety of tofacitinib in patients with moderate-to-severe RA and inadequate response to methotrexate and at least one cardiovascular risk factor to evaluate safety events of interest, including cardiovascular adverse events, opportunistic infections, and malignancy.
Due to safety concerns that arose from this clinical trial, FDA conducted an analysis in the Sentinel System to better understand the characteristics of users of tofacitinib compared to other disease-modifying anti-rheumatic drugs (DMARD) - conventional DMARDs, JAK inhibitors, tumor necrosis factor (TNF) inhibitor or other biologics users-, with a focus on RA severity and utilization patterns. Results indicated RA severity could not be reliably identified from the Sentinel Distributed Database’s administrative claims data alone. Given that identifying RA severity was critical to this assessment, no additional Sentinel analyses were pursued.
After a comprehensive review of the available information, the FDA added a Boxed Warning to tofacitinib’s label in July 2019, indicating that “rheumatoid arthritis patients with at least one cardiovascular (CV) risk factor had a higher rate of all-cause mortality and thrombosis with XELJANZ 10 mg twice daily vs. 5 mg twice daily or TNF blockers.”