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Tofacitinib Effective as Monotherapy or Adjunct for Refractory RA

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We Already Have a Range of Biologic and Conventional RA Drugs

The findings of Dr. Fleishmann and colleagues, and of Dr. van Vollenhoven and colleagues, must be confirmed in longer-term studies with radiographic end points, which were not assessed in either of these phase III clinical trials, said Dr. David A. Fox.

Moreover, it is not yet clear which RA patients would benefit from tofacitinib, "considering that there are currently nine biologic medications (directed at five distinct molecular targets)" that are Food and Drug Administration approved "for use in patients with RA, along with a range of effective conventional disease-modifying drugs that generally have good side-effect profiles," he noted.

Dr. Fox is in the division of rheumatology within the department of internal medicine at the University of Michigan, Ann Arbor. He reported ties to Lycera, Genentech, Johnson & Johnson, Karyopharma, and Roche. These remarks were taken from his editorial accompanying the two reports on tofacitinib (New Engl. J. Med. 2012;367:565-7).


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

The three efficacy end points were the same as those in the ORAL-Solo study.

At 6 months, the percentages of patients who met criteria for an ACR 20 response were significantly higher with both doses of tofacitinib and with adalimumab than with placebo, and the magnitudes of the treatment effect were similar between tofacitinib and adalimumab (5-mg tofacitinib, 51.5%; 10-mg tofacitinib, 52.6%; adalimumab, 47.2%; placebo, 28.3%).

Similarly, the percentages of patients who showed significant improvement on both the HAQ-DI score and the DAS28-4(ESR) score were significantly higher with both tofacitinib and adalimumab than with placebo, Dr. van Vollenhoven and his colleagues said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1112072]).

As in the ORAL-Solo study, the treatment responses in the ORAL-Standard study were rapid and were sustained throughout the 1-year study period.

Also as in the ORAL-Solo study, serious adverse events – including serious infections such as tuberculosis – were significantly higher with tofacitinib than with either adalimumab or placebo. Notable adverse events included cytopenia, respiratory and urinary tract infections, and gastrointestinal side effects.

Tofacitinib also raised cholesterol and serum creatinine levels. "Given the duration and size of the study, the implications ... for the risk of cardiac events ... could not be assessed. Longer-term monitoring of patients receiving tofacitinib is ongoing," Dr. van Vollenhoven and his associates said.

Both studies were funded by Pfizer. The investigators reported numerous ties to industry sources.

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