FDA Approves Tofacitinib for Rheumatoid Arthritis

Megan Brooks

November 06, 2012

The US Food and Drug Administration (FDA) today approved tofacitinib (Xeljanz, Pfizer) to treat adults with moderately to severely active rheumatoid arthritis (RA) who have not responded adequately to, or are intolerant of, methotrexate.

Tofacitinib is the first selective oral Janus kinase (JAK) inhibitor to be approved. It interrupts signaling of several cytokines involved in immune response.

"Xeljanz provides a new treatment option for adults suffering from the debilitating disease of RA who have had a poor response to methotrexate," Badrul Chowdhury, MD, PhD, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research, said in a statement.

In May 2012, as reported by Medscape Medical News, an FDA Arthritis Advisory Committee voted 8-2 to recommend the approval of tofacitinib.

The FDA said today that tofacitinib was approved ahead of the product's prescription drug user fee goal date of November 21, 2012, the date the agency was scheduled to complete review of the drug application.

The safety and effectiveness of the drug were evaluated in 7 clinical trials in adult patients with moderately to severely active RA. In all of the trials, patients treated with tofacitinib saw improvement in clinical response and physical functioning compared with patients treated with placebo. Two of the phase 3 trials were published in the New England Journal of Medicine on August 9 and were reported by Medscape Medical News at that time.

The most common adverse reactions in clinical trials were upper respiratory tract infections, headache, diarrhea, and inflammation of the nasal passage and the upper part of the pharynx.

In clinical trials, tofacitinib was associated with an increased risk for serious infections, including opportunistic infections, tuberculosis, cancers, and lymphoma. The drug carries a Boxed Warning regarding these safety risks, the FDA said. The drug is also associated with increases in cholesterol and liver enzyme test results and decreases in blood counts.

The FDA said it approved tofacitinib with a risk evaluation and mitigation strategy (REMS), "which consists of a Medication Guide advising patients about important safety information and a communication plan to inform health care providers about the serious risks associated with Xeljanz."

"To study the long-term effects of Xeljanz on heart disease, cancer, and serious infections, the FDA is requiring a postmarketing study that will evaluate two doses of Xeljanz and include a group of patients on another approved treatment to serve as a comparison," the agency said.