A 10-mg dose of tofacitinib twice daily was significantly more effective than placebo for inducing remission in ulcerative colitis patients, based on data from a group of three randomized trials totaling approximately 1,500 adults. The findings were published online May 3 in the New England Journal of Medicine (2017;376:1723-36).

The series of OCTAVE trials (Oral Clinical Trials for Tofacitinib in Ulcerative Colitis) included adults with moderately to severely active ulcerative colitis (UC). Patients were randomized to 10 mg of tofacitinib, 5 mg tofacitinib, or placebo. The studies were conducted over a 4-year period, at 144 sites for OCTAVE 1, 169 sites for OCTAVE 2, and 297 sites for OCTAVE Sustain.

The primary endpoints of the OCTAVE 1 and OCTAVE 2 induction trials were remission at 8 weeks (defined as a Mayo score of 2 or less, with no subscore less than 1 and a rectal bleeding subscore of 0). The primary endpoint of the OCTAVE Sustain trial was remission at 52 weeks.

In both OCTAVE 1 and OCTAVE 2, the remission rates at 8 weeks were significantly higher in the 10-mg tofacitinib groups, compared with the placebo groups (18.5% vs. 8.2%, respectively; 16.6% vs. 3.6%, respectively). The rate of remission at 52 weeks was significantly higher in the 5-mg and 10-mg tofacitinib groups (34.3% and 40.6%, respectively) than in the placebo group (11.1%) in the OCTAVE Sustain trial.

In addition, rates of mucosal healing were greater in the tofacitinib group than in the placebo group at 8 weeks and 52 weeks.

“Pharmacokinetic results in the OCTAVE trials did not indicate a decrease in plasma tofacitinib concentrations during the course of treatment at any given dose in individual patients. These results are consistent with the previously established physicochemical characteristics and clearance mechanisms of tofacitinib,” noted William J. Sandborn, MD , of the University of California, San Diego, and his colleagues.

In the OCTAVE 1 trial, serious adverse events occurred in 4.2% and 8.0% of patients in the 10-mg and placebo groups, respectively. In the OCTAVE 2 trial, they occured in 3.4% and 4.1% of the 10-mg and placebo groups, respectively. The rate of serious adverse events in the OCTAVE Sustain trial was 5.1%, 5.6%, and 6.6% in the 10-mg, 5-mg, and placebo groups, respectively. Tofacitinib was associated with increased lipid levels, as well as higher rates of overall infection and herpes zoster infection, compared with placebo.

The study was supported by Pfizer. Lead author Dr. Sandborn and several coauthors disclosed financial relationships with multiple companies including Pfizer.