Tofacitinib as induction and maintenance therapy for ulcerative colitis

William J. Sandborn, Chinyu Su, Bruce E. Sands, Geert R. D'Haens, Séverine Vermeire, Stefan Schreiber, Silvio Danese, Brian G. Feagan, Walter Reinisch, Wojciech Niezychowski, Gary Friedman, Nervin Lawendy, Dahong Yu, Deborah Woodworth, Arnab Mukherjee, Haiying Zhang, Paul Healey, Julian Panés

Research output: Contribution to journalArticle

Abstract

Copyright © 2017 Massachusetts Medical Society. 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.).
Original languageEnglish
Pages (from-to)1723-1736
Number of pages14
JournalNew England Journal of Medicine
Volume376
Issue number18
DOIs
Publication statusPublished - May 4 2017

Fingerprint Dive into the research topics of 'Tofacitinib as induction and maintenance therapy for ulcerative colitis'. Together they form a unique fingerprint.

  • Cite this

    Sandborn, W. J., Su, C., Sands, B. E., D'Haens, G. R., Vermeire, S., Schreiber, S., Danese, S., Feagan, B. G., Reinisch, W., Niezychowski, W., Friedman, G., Lawendy, N., Yu, D., Woodworth, D., Mukherjee, A., Zhang, H., Healey, P., & Panés, J. (2017). Tofacitinib as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine, 376(18), 1723-1736. https://doi.org/10.1056/NEJMoa1606910