*Acute severe colitis
*Mild-to-Moderate Ulcerative Colitis
*Probiotics in Ulcerative Colitis
*Methotrexate in Ulcerative Colitis
*Infliximab Ulcerative Colitis
*Infliximab with Azathiopurine (Ulcerative Colitis)
*Acute severe colitis: Accelerated induction Infliximab
*Adalimumab in Ulcerative Colitis (ULTRA studies)
*Golimumab in Ulcerative Colitis
*Vedolizumab vs Adalimumab Ulcerative Colitis
*Vedolizumab Ulcerative Colitis
*Ustekinumab (Ulcerative colitis)
*Acute severe colitis: Infliximab vs ciclosporin (CONTRUCT)
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis (2017)
William J. Sandborn, M.D., Chinyu Su, M.D., Bruce E. Sands, M.D., Geert R. D’Haens, M.D., Séverine Vermeire, M.D., Ph.D., Stefan Schreiber, M.D., Silvio Danese, M.D., Brian G. Feagan, M.D., Walter Reinisch, M.D., Wojciech Niezychowski, M.D., Gary Friedman, M.D., Nervin Lawendy, Pharm.D., Dahong Yu, M.D., Ph.D., Deborah Woodworth, M.B.A., Arnab Mukherjee, Ph.D., Haiying Zhang, Ph.D., Paul Healey, M.D., and Julian Panés, M.D., for the OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators
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.
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.
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.
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.).