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http://hdl.handle.net/2445/189961
Title: | Tofacitinib as induction and maintenance therapy for ulcerative colitis |
Author: | Sandborn, William J. Su, Chinyu Sands, Bruce E. D'Haens, Geert R. Vermeire, Séverine Schreiber, Stefan Danese, Silvio Feagan, Brian G. Reinisch, Walter Niezychowski, Wojciech Friedman, Gary Lawendy, Nervin Yu, Dahong Woodworth, Deborah Mukherjee, Arnab Zhang, Haiying Healey, Paul Panés Díaz, Julià OCTAVE Induction 1 OCTAVE Induction 2 OCTAVE Sustain Investigators. Guardiola, Jordi |
Keywords: | Colitis ulcerosa Quimioteràpia Inhibidors enzimàtics Ulcerative colitis Chemotherapy Enzyme inhibitors |
Issue Date: | 4-May-2017 |
Publisher: | Massachusetts Medical Society |
Abstract: | 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.) |
Note: | Reproducció del document publicat a: https://doi.org/10.1056/NEJMoa1606910 |
It is part of: | New England Journal of Medicine, 2017, vol. 376, num. 18, p. 1723-1736 |
URI: | http://hdl.handle.net/2445/189961 |
Related resource: | https://doi.org/10.1056/NEJMoa1606910 |
ISSN: | 0028-4793 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) |
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