Tofacitinib: Additional Phase III data

Additional data from the double-blind, international Phase III ORAL Standard (1064) trial in 717 patients who had an inadequate response to methotrexate showed that twice-daily 5 and 10 mg oral tofacitinib led to ACR20 response rates at 6 months of 51.5% and 52.6%, respectively, vs. 28.3% for placebo (p<0.001 for both). Low- and high-dose tofacitinib also improved HAQ-DI scores from baseline to 3 months by 0.55 and 0.61 points, respectively, vs. 0.24 points for placebo (p<0.001 for both). Furthermore, 6.2% and 12.5% of patients receiving low- and high-dose tofacitinib, respectively, achieved a DAS28 score of <2.6 at 6 months vs. 1.1% of patients receiving placebo (p<0.05 and p<0.001, respectively). Additionally, the active control 40 mg subcutaneous adalimumab led to an ACR20 response rate of 47.2%, improved mean HAQ-DI score by 0.49 points and 6.7% of patients receiving adalimumab achieved a DAS28 score of <2.6.

Adverse events occurred more frequently with tofacitinib vs. placebo, with 2 patients in the high-dose tofacitinib arm developing pulmonary tuberculosis. Tofacitinib was also associated with increases in low- and high-density lipoprotein cholesterol levels. Patients received twice-daily 5 or 10 mg oral tofacitinib, 40 mg subcutaneous adalimumab every other week, or placebo. At 3 months, non-responding placebo-treated patients were switched to tofacitinib for the remainder of the study. After 6 months of treatment, all patients randomized to the placebo group were switched to tofacitinib. Data were published in the New England Journal of Medicine. Last year, Pfizer reported that tofacitinib met the 3 co-primary endpoints vs. placebo and led to numerically similar results to that of adalimumab (see BioCentury, May 2, 2011 & Sept. 12, 2011). ...