Two studies in the phase 3 OCTAVE (Oral Clinical Trials for Tofacitinib in Ulcerative Colitis) program have met their primary endpoints. At week 8, a significantly greater proportion of patients receiving tofacitinib (Xeljanz, Pfizer) 10 mg twice daily (BID) were in remission compared with patients given placebo (18.5% vs. 8.2%, respectively) in the OCTAVE Induction 1 trial. These results were consistent with findings from the OCTAVE Induction 2 trial, in which a significantly greater proportion of patients treated with tofacitinib 10 mg BID were in remission compared with those given placebo (16.6% vs. 3.6%, respectively) at week 8. Remission was defined as a Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and a rectal bleeding subscore of 0.
In addition, a significantly greater number of patients receiving tofacitinib 10 mg BID achieved mucosal healing at week 8 compared with placebo-treated patients—the key secondary endpoint in both studies. In the OCTAVE Induction 1 trial, 31% of patients receiving tofacitinib 10 mg BID achieved mucosal healing compared with 16% of the placebo group at week 8. Similar results were seen in OCTAVE Induction 2 trial, with 28% of patients receiving tofacitinib 10 mg BID achieving mucosal healing compared with 12% of those given placebo at week 8. Mucosal healing is defined by a Mayo endoscopic subscore of 0 or 1.
Across both studies, a similar proportion of patients in the tofacitinib groups and the placebo groups reported adverse events (AEs) or serious AEs (SAEs) through week 8. In the OCTAVE Induction 1 study, the rates of AEs and SAEs were 57% and 3% in the tofacitinib group compared with 60% and 4% of the placebo group, respectively. In the OCTAVE Induction 2 trial, the rates of AEs and SAEs were 54% and 4% in the tofacitinib group compared with 53% and 8% in the placebo group, respectively.
In OCTAVE Induction 1 and 2 studies, treatment-emergent AEs were reported in 57% and 54% of patients treated with tofacitinib compared with 60% and 53% of patients treated with placebo, respectively. In both studies, the most common AE leading to discontinuation across all treatment groups was ulcerative colitis flare. Moreover, in both studies, the rates of discontinuations due to AEs were 4% and 4% in the tofacitinib group compared with 2% and 7% in the placebo group, respectively.
Tofacitininb, a Janus kinase (JAK) inhibitor, is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well. Tofacitininb may be used as a single agent or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). The use of tofacitininb in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.
Source: Pfizer; March 18, 2016.