This Tuesday tofacitinib citrate (brand name Xeljanz) became the first Janus kinase (JAK) inhibitor to receive FDA approval for the treatment of rheumatoid arthritis (RA). Tofacitinib citrate is also the first new oral disease-modifying antirheumatic drug (DMARD) to be approved for RA in over a decade.
Tofacitinib works differently than other DMARDs. JAK inihibitors block a signaling protein (Janus kinases, JAK) that would otherwise relay immune signals from certain proteins on the outside of white blood cells to the inside and kick off immune activity. And whereas many biologics are administered by injection, tofacitinib has been approved as a twice-daily 5 milligram pill. Because it can be taken orally, tofacitinib is expected to compete well against the popular biologic drug adalimumab (brand name Humira), which is administered through regular shots.
In a press release, Badrul Chowdhury, MD, PhD, of the FDA’s Center for Drug Evaluation and Research was quoted as saying, “Xeljanz provides a new treatment option for adults suffering from the debilitating disease of RA who have had a poor response to methotrexate.” The release states that in seven clinical trials, tofacitinib did better than placebo in improving the function and clinical response in people with RA.
In a study published this August in The New England Journal of Medicine, researchers compared the effects of tofacitinib to those of adalimumab and placebo in people who were already taking methotrexate (brand name Rheumatrex, Trexall). At the end of six months, more than half of the people taking tofacitinib saw an at least 20% improvement in their RA(as measured by an established set of criteria for RA severity), as opposed slightly less than half of those taking adalimumab, and a little over a quarter of people taking a placebo.
Another study published in the same issue tested two dose sizes of tofacitinib for six months. Participants in the study were randomly assigned to one of four groups, two of which received one of the two doses of tofacitinib, and two of which started on a placebo and were switched to one of the two tofacitinib doses halfway through. At the halfway point, about 60% of the people taking the smaller dose of tofacitinib and about 66% of the people taking the larger dose had at least a 20% improvement in their RA, as opposed to a little over a quarter of the people on placebo. People taking tofacitinib were also more than twice as likely as people taking placebo to have an improvement of 50% or more at the three-month mark (more than 30% of people taking either dose).
As with most drugs, there are also risks with taking tofacitinib. Both studies reported adverse events, including tuberculosis. An editorial that appeared in the same issue of The New England Journal of Medicine mentioned that other biologic drugs, such as TNF inhibitors, have been known to induce autoimmune conditions in addition to the one they treat, and there could be a similar risk with tofacitinib.
Four people taking tofacitinib as part of a study presented at a European conference in 2011 died. However, Pfizer, the maker of the drug, was quick to point out that only one of the deaths — from respiratory failure — was clearly linked to tofacitinib.
Tuesday’s press release from the FDA also warns that tofacitinib is linked to an increased risk of cancers, including lymphoma, and infections, including tuberculosis. Tofacitinib has also been known to increase cholesterol levels and lower blood cell counts, and has been associated with headache, nasal inflammation, and diarrhea. The FDA is calling for further study of tofacitinib’s potential risks following its approval.