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Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

Feagan, BG; Sandborn, WJ; Gasink, C; Jacobstein, D; Lang, Y; Friedman, JR; Blank, MA; Johanns, J; Gao, L-L; Miao, Y; et al. Feagan, BG; Sandborn, WJ; Gasink, C; Jacobstein, D; Lang, Y; Friedman, JR; Blank, MA; Johanns, J; Gao, L-L; Miao, Y; Adedokun, OJ; Sands, BE; Hanauer, SB; Vermeire, S; Targan, S; Ghosh, S; de Villiers, WJ; Colombel, J-F; Tulassay, Z; Seidler, U; Salzberg, BA; Desreumaux, P; Lee, SD; Loftus, EV; Dieleman, LA; Katz, S; Rutgeerts, P (2016) Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. New England Journal of Medicine, 375 (20). pp. 1946-1960. ISSN 0028-4793 https://doi.org/10.1056/NEJMoa1602773
SGUL Authors: Pollok, Richard Charles G

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Abstract

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.)

Item Type: Article
Additional Information: From New England Journal of Medicine, Brian G. Feagan, M.D., William J. Sandborn, M.D., Christopher Gasink, M.D., Douglas Jacobstein, M.D., Yinghua Lang, M.A., Joshua R. Friedman, M.D., Ph.D., Marion A. Blank, Ph.D., Jewel Johanns, Ph.D., Long-Long Gao, Ph.D., Ye Miao, M.S., Omoniyi J. Adedokun, M.S., R.Ph., Bruce E. Sands, M.D., Stephen B. Hanauer, M.D., Severine Vermeire, M.D., Ph.D., Stephan Targan, M.D., Subrata Ghosh, M.D., Willem J. de Villiers, M.D., Ph.D., Jean-Frédéric Colombel, M.D., Zsolt Tulassay, M.D., Ursula Seidler, M.D., Bruce A. Salzberg, M.D., Pierre Desreumaux, M.D., Scott D. Lee, M.D., Edward V. Loftus, Jr., M.D., Levinus A. Dieleman, M.D., Ph.D., Seymour Katz, M.D., and Paul Rutgeerts, M.D., Ph.D., for the UNITI–IM-UNITI Study Group, Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease, 375, 1946-1960. Copyright © (2016) Massachusetts Medical Society. Reprinted with permission.
Keywords: General & Internal Medicine, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: New England Journal of Medicine
ISSN: 0028-4793
Dates:
DateEvent
17 November 2016Published
Publisher License: Publisher's own licence
URI: https://openaccess.sgul.ac.uk/id/eprint/109401
Publisher's version: https://doi.org/10.1056/NEJMoa1602773

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