The Janus kinase inhibitor tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis, has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate, the Food and Drug Administration announced on Nov. 6.
Tofacitinib is a small-molecule inhibitor of the Janus kinase (JAK) pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.
It has been approved with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a postmarketing study, according to the FDA’s statement announcing the approval.
Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.
Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.
The postmarketing study will compare two doses of tofacitinib with another approved treatment for RA.
At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.
Pfizer is marketing the drug as Xeljanz. Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.