Tofacitinib rapidly improves RA signs and symptoms

Dr. Kremer and his associates' report is a good study that will reassure rheumatologists that it is possible to use tofacitinib with nonbiologic DMARDs. It also reinforces that the dose of tofacitinib that is approved in North America is too low for many patients. There is a nice dose response for DAS28 remission (placebo, 2.6%; tofacitinib, 5 mg twice daily, 8.5%; tofacitinib 10 mg twice daily, 12.5%) and HAQ-DI (-0.16, -0.44, and -0.53, respectively). This was less the case for the ACR20 responses (30.8%, 52.1%, and 56.6%, respectively), but even here there is some trend toward a dose response.

On the other hand, there are some aspects of this study that could be clearer. The patients themselves had long disease duration and relatively high disease activity, so it is not clear that the results apply to all patients. Furthermore, about 10% of patients were on biologics prior to entering the study, and it is not clear how long those biologics had actually been stopped. (The inclusion criteria were not very clear on this aspect.) The patients were allowed on more than one DMARD, and it would have been good to know the breakdown of responses by the number of concomitant DMARDs. Also, nearly 60% of the patients were on corticosteroids, and there is no discussion of the effect of this drug on response or toxicity. Finally, the breakdown of patients was about 20% on placebo initially, compared with 80% on initial tofacitinib, thus introducing the possibility of an unbalanced early response.

The bottom line is that this article is generally reassuring and allows rheumatologists to use tofacitinib more broadly. It reinforces the need for sufficient data to allow higher doses of drugs to be approved in the United States, but, like many studies, leaves many questions (especially on how to consider combinations and corticosteroids) and does not allow the degree of generalization that would have been ideal.

Daniel E. Furst, M.D., is the Carl M. Pearson Professor of Rheumatology at the at the University of California, Los Angeles. He has been a consultant to Pfizer and has received travel support and meals from the company. He has also been a consultant to or received grant support from other pharmaceutical companies marketing drugs for rheumatoid arthritis, including Abbott, Amgen, and Bristol-Myers Squibb.