First effective oral RA drug

Rheumatoid arthritis (RA) patients will be keeping their fingers crossed that the first oral immune-mediator treatment for the disease will be approved by the FDA. Pfizer s tofacitinib has made it through phase III trials, bringing it one step closer to the pharmacy at least, so hope the over one million RA sufferers in the U.S.

According to two studies published in The New England Journal of Medicine, a new immunomodulator drug, tofacitinib, was found to provide symptomatic benefits, in addition to improved physical functioning even when given without methotrexate, the current standard treatment for RA. The drug works via a new (to RA treatment) mechanism: inhibition of JAK, an inflammation-causing enzyme.

In the first study, led by Dr. Roy Fleischmann of the Metroplex Clinical Research Center in Dallas, two-thirds of the group receiving the new drug improved within three months, as compared to one-quarter of the control subjects.

The second study, led by Dr. Ronald van Vollenhoven of the Karolinska Institute in Stockholm, tested patients who were also taking methotrexate. Researchers similarly saw a 20 percent improvement in six months for over half of the tofacitinib-treated patients. In comparison, the placebo group, as in the first trial, saw improvement in only 29 percent of patients. Furthermore, the second trial also had a comparator arm, in which patients received a different type of immune-mediator drug, Humira. That group had a 20 percent improvement for only 48 percent of patients.

An estimated 1.5 million Americans are currently suffering from RA, says ACSH s Dr. Gilbert Ross, and many of those patients do not respond to conventional therapy. Even though the introduction of immune-mediator treatments over the past twenty years has made a major improvement in treating this disabling disease, there s plenty of room for a new, effective oral drug like hopefully tofacinitib. But more studies are needed to prove its efficacy.

Although tofacitinib has shown impressive results, the benefits seen with the new drug should be taken with a grain of salt. In both trails, tofacitinib treatment was associated with a number of adverse side effects, including increased levels of low-density lipoprotein (LDL) cholesterol, reduced neutrophil count, and an increased number of infections.

Dr. David A. Fox of the University of Michigan in Ann Arbor wrote, in an accompanying editorial, A better understanding of the safety profile of tofacitinib will influence the consideration of when in the course of rheumatoid arthritis clinicians should consider this novel approach.