BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was 
shown to have potential efficacy as induction therapy for ulcerative colitis in 
a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction 
and maintenance therapy.
METHODS: We conducted three phase 3, randomized, double-blind, 
placebo-controlled trials of tofacitinib therapy in adults with ulcerative 
colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, 
respectively, who had 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. The primary end point was remission at 8 
weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to 
induction therapy were randomly assigned to receive maintenance therapy with 
tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The 
primary end point was remission at 52 weeks.
RESULTS: In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% 
of the patients in the tofacitinib group versus 8.2% in the placebo group 
(P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 
3.6% (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% in the 10-mg 
tofacitinib group versus 11.1% in the placebo group (P<0.001 for both 
comparisons with 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. Across all 
three trials, adjudicated nonmelanoma skin cancer occurred in five patients who 
received tofacitinib and in one who received placebo, and adjudicated 
cardiovascular events occurred in five who received tofacitinib and in none who 
received placebo; as compared with placebo, tofacitinib was associated with 
increased lipid levels.
CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, 
tofacitinib was more effective as induction and maintenance therapy than 
placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE 
Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 
, respectively.).