Tofacitinib more effective than placebo for ulcerative colitis, industry-funded study finds

The drug was evaluated in three multicenter, phase 3, randomized, double-blind, placebo-controlled trials involving patients with moderately to severely active disease.


Tofacitinib, an oral, small-molecule Janus kinase inhibitor currently FDA-approved for rheumatoid arthritis, was more effective as induction and maintenance therapy for moderately to severely active ulcerative colitis than placebo, an industry-funded study found.

Researchers evaluated the efficacy of tofacitinib in three multicenter, phase 3, randomized, double-blind, placebo-controlled trials. Moderately to severely active ulcerative colitis was defined as a Mayo score of 6 to 12, with a rectal bleeding subscore of 1 to 3 and an endoscopic subscore of 2 or 3. Scores on the Mayo scale range from 0 to 12, and scores on each of the four subscores range from 0 to 3, with higher scores indicating more severe disease.

In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, with moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib, 10 mg twice daily, or placebo for 8 weeks. Remission at eight weeks was the primary end point.

Patients who completed one of those trials and had a clinical response were eligible to participate in the OCTAVE Sustain trial. Clinical response was defined as a decrease from induction-trial baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. There were 593 patients who had a clinical response and were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. Remission at 52 weeks was the primary end point.

The trials were funded and supported by Pfizer. Results were published May 4 by the New England Journal of Medicine.

In the OCTAVE Induction 1 trial, remission at eight weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% of the placebo group (P=0.007). In the OCTAVE Induction 2 trial, remission occurred in 16.6% of treated patients versus 3.6% on placebo (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% of the 10-mg tofacitinib group versus 11.1% of the placebo group (P<0.001 for both doses compared to placebo).

In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. The authors noted that most cases of herpes zoster affected one dermatome or two adjacent dermatomes. None led to discontinuation, and the infections are consistent with uses of tofacitinib for indications other than ulcerative colitis, the authors said.

“In conclusion, among patients with moderately to severely active ulcerative colitis, therapy with tofacitinib at a dose of 10 mg twice daily was more effective than placebo for induction of remission and mucosal healing,” the authors wrote. “Maintenance therapy with tofacitinib at a dose of either 5 mg or 10 mg twice daily was more effective than placebo in sustaining remission and mucosal healing.”

An editorial stated that the trial had many high-quality elements, such as a large, international patient population with enrollment criteria that would apply to typical patients. Yet the drug will need further study, the author continued. “Regardless of its eventual place in the treatment algorithm for ulcerative colitis, tofacitinib is a new class of therapy that has efficacy.”