Ustekinumab induction and maintenance therapy in refractory Crohn's disease

William J. Sandborn*, Christopher Gasink, Long Long Gao, Marion A. Blank, Jewel Johanns, Cynthia Guzzo, Bruce E. Sands, Stephen B. Hanauer, Stephan Targan, Paul Rutgeerts, Subrata Ghosh, Willem J S De Villiers, Remo Panaccione, Gordon Greenberg, Stefan Schreiber, Simon Lichtiger, Brian G. Feagan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

637 Scopus citations

Abstract

BACKGROUND: In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. METHODS: We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS: The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P = 0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P = 0.03) and response (69.4% vs. 42.5%, P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.)

Original languageEnglish (US)
Pages (from-to)1519-1528
Number of pages10
JournalNew England Journal of Medicine
Volume367
Issue number16
DOIs
StatePublished - Oct 18 2012

ASJC Scopus subject areas

  • Medicine(all)

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