Tofacitinib: Additional Phase III data

Additional data from the double-blind, placebo-controlled Phase III ORAL Scan (1044) trial in 535 evaluable patients with moderate to severe active RA who had an inadequate response to methotrexate showed that twice-daily 5 and 10 mg oral tofacitinib plus methotrexate maintained efficacy improvements at 2 years in ACR response rates, mTSS, DAS28 score of <2.6 points and HAQ-DI scores. Specifically, ACR20 response rates at 2 years were 73.5% for low-dose tofacitinib and 82.6% for high-dose tofacitinib, while ACR50 response rates were 48.8% and 65.1%, respectively. ACR70 response rates at 2 years were 27% in the low-dose arm and 40.4% in the high-dose arm. Patients receiving low-dose tofacitinib had a 0.48 point increase in mTSS, while patients in the high-dose arm had a 0.23 point increase. Additionally, 16.8% of patients in the low-dose tofacitinib arm and 20.7% of patients in the high-dose tofacitinib arm achieved a DAS28 score of <2.6 points at 2 years. Furthermore, patients receiving low-dose tofacitinib had a 0.5 point reduction in HAQ-DI score, while patients in the high-dose arm had a 0.65 point reduction. Data will be presented at the American College of Rheumatology meeting in Washington in November.

Pfizer previously reported 1-year data from the ORAL Scan trial in 800 patients showing that high-dose tofacitinib met the 4 co-primary endpoints of ACR20 response rate at 6 months, of reducing the progression of structural damage as measured by mTSS at 6 months, of improving physical function as measured by HAQ-DI scores at 3 months, and of a greater proportion of patients achieving a DAS28 score of <2.6 points at 6 months vs. placebo. The twice-daily 5 mg tofacitinib dose met the ACR20 endpoint, but missed the mTSS endpoint. Pfizer said that due to a pre-specified step-down statistical procedure, no further testing on the HAQ-DI or DAS28 endpoints for the 5 mg dose was performed (see BioCentury, April 18, 2011). ...