Tofacitinib (Xeljanz) Inhibits Joint Damage in Arthritis Trial
Radiographic scores significantly better versus placebo (Feb. 28)
In a planned 12-month interim analysis of an ongoing phase III radiographic study, treatment with oral tofacitinib (Xeljanz, Pfizer) inhibited structural joint damage in patients with rheumatoid arthritis (RA) who had shown an inadequate response to methotrexate (MTX). The new findings were published in the March issue of Arthritis & Rheumatism.
In the double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomly assigned to treatment with either tofacitinib (5 mg or 10 mg twice daily) or placebo. At month 3, nonrespnders in the placebo group were switched to the tofacitnib regimens; remaining placebo-treated patients were advanced to tofacitinib at 6 months.
At the 3-month time point, least squares mean (LSM) changes in the Health Assessment Questionnaire disability index score were significantly different between tofacitinib 10 mg twice daily and placebo (–0.54 vs. –0.15, respectively; P < 0.0001).
At the 6-month time point, both the tofacitinib 5 mg twice daily and the tofacitinib 10 mg twice daily treatment groups had significantly higher response rates, according to the American College of Rheumatology 20% improvement (ACR20) criteria, compared with the placebo group (51.5% and 61.8% vs. 25.3%, respectively; both P < 0.0001). In addition, patients receiving tofacitinib 10 mg twice daily showed a change from baseline in radiographic scores of 0.06 units, compared with a change of 0.47 units in those given placebo (P = 0.05). However, the changes in radiographic scores were not significantly different between tofacitinib 5 mg twice daily and placebo (0.12 units vs. 0.06 units, respectively; P = 0.0792). Remission rates (defined as a value of less than 2.6 on the four-variable Disease Activity Score in 28 joints, using the erythrocyte sedimentation rate) were also significantly higher for tofacitinib 10 mg twice daily compared with placebo (16.0% vs. 1.6%, respectively; P < 0.0001).
The most common adverse events during the first 12 months of the trial were infections, gastrointestinal disturbances, and laboratory abnormalities. Seven opportunistic infections occurred in patients receiving tofacitinib, and there were five deaths in the active treatment groups. The causes of death included pneumonia, lung cancer, and renal failure.
“Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX,” the authors concluded.
Source: Wiley; February 28, 2013.