Tofacitinib was superior to methotrexate at reducing the signs and symptoms of rheumatoid arthritis, improving physical function, and slowing the progression of joint damage in a 2-year, phase III clinical trial sponsored by Pfizer.
The results of the study indicate that tofacitinib "can be more effective clinically, functionally, and radiographically than methotrexate in patients with rheumatoid arthritis who have not previously received methotrexate," Dr. Eun-Bong Lee of Seoul (South Korea) National University and his associates reported June 19 in the New England Journal of Medicine.
While nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs) in combination with methotrexate have been shown to be superior to methotrexate alone, other studies have not shown superiority of a biologic DMARD alone vs. methotrexate at times extending to 1 year or longer, they noted.
Tofacitinib (Xeljanz), a targeted, small-molecule Janus kinase inhibitor, was approved by the Food and Drug Administration in November 2012 for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate.
In the trial conducted at 151 medical centers worldwide, 956 adults with active, moderate to severe RA who had never received methotrexate or tofacitinib were randomly assigned to receive 5 mg of oral tofacitinib twice daily (373 patients), 10 mg of oral tofacitinib twice daily (397 patients), or methotrexate (186 patients) for 2 years. The mean duration of RA at entry into the study was approximately 3 years, the investigators wrote.
At 6, 12, and 24 months, there was no decline in van der Heijde modified total Sharp score (a radiographic measure of structural joint damage), as well as on measures of joint erosion and joint-space narrowing, in a significantly greater proportion of patients who were taking tofacitinib than in those who were taking methotrexate. In addition, 25.5% of the patients taking 5 mg of tofacitinib and 37.7% of those taking 10 mg of tofacitinib achieved an American College of Rheumatology (ACR) 70 response (at least a 70% reduction in the number of tender and swollen joints plus equivalent improvement in three to five ACR core measures), compared with only 12.0% of patients in the methotrexate group.
Rates of remission and of low disease activity at 6, 12, and 24 months also were significantly higher in the two tofacitinib groups than in the methotrexate group, the investigators reported (N. Engl. J. Med. 2014;370:2377-86).
However, "the benefits of tofacitinib need to be considered in the context of the risks of adverse events," the authors wrote. As expected, the drug was associated with declines in neutrophil and lymphocyte counts, and with increases in lipid, aminotransferase, and creatinine levels. Herpes zoster infections developed in 4% of the two tofacitinib groups, compared with only 1.1% of the methotrexate group. *Five confirmed cases of cancer (non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, prostate cancer, Burkitt’s B-cell lymphoma, and colon cancer) and one case of adrenal adenoma with unknown malignancy status developed in the tofacitinib group, compared with one confirmed case of cancer (gastric) in the methotrexate group.
This study was funded by Pfizer, which also collected and analyzed the data and assisted with writing the report. Dr. Lee reported receiving consulting fees from Pfizer; Dr. Lee’s associates reported ties to numerous industry sources.
*Correction, 7/1/2014: An earlier version of this story misstated the total number of confirmed cancers in the tofacitinib groups.