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N Engl J Med. 2012 Oct 18;367(16):1519-28. doi: 10.1056/NEJMoa1203572.

Ustekinumab induction and maintenance therapy in refractory Crohn's disease.

Collaborators (170)

Haas T, Kaser A, Vogelsang H, Brown S, Florin T, Gibson PG, Hetzel D, Leong R, Leong R, Pavli P, Radford-Smith G, Sparrow M, Baert F, D'Haens G, D'Heygere F, Franchimont D, Louis E, Mana F, Moreels T, Vermeire S, Anderson F, Axler J, Greenbloom S, Bitton A, Fedorak RN, Larkai E, Marshall J, Singh R, Abitbol V, Allez M, Lemann M, Bonaz B, Colombel JF, Dupas JL, Hebuterne X, Laharie D, Lerebours E, Moreau J, Bokemeyer B, Holler B, Howaldt SP, Krummenerl T, Kucharzik T, Ochsenkühn T, Raedler A, Schiefke I, Seidler U, Sturm A, Zeitz M, Eliakim A, Fishman S, Konikoff FM, Lavy A, Niv Y, Nussinson E, Rachmilewitz D, Andriulli A, Annese V, Biancone L, Corazza GR, Danese S, Sturniolo GC, Terrosu G, Sorrentino D, Hommes DW, Jansen JM, Otten MH, Pierik M, Ponsioen CY, Stokkers P, van Bodegraven AA, Van der Woude J, Calvet Calvo X, Casellas F, Garcia López S, Garcia-Planella E, Ginard-Vincens D, López San Román A, Muñoz Nuñez F, Pérez Gisbert J, Vera MI, Rodrigo J, Riestra-Menendez S, Arnott I, Bloom S, Campbell SS, Harbord MW, Mansfield JC, Nwokolo C, Parkes M, Probert CS, Aberra FN, Abraham BP, Abreu MT, Amontree JS, Barish CF, Barto AE, Behm B, Birbara CA, Bologna S, Dryden GW Jr, Eisner MS, Ertan A, Fogel R, Gagneja HK, Ginsburg P, Goff JS, Gordon G, Hamilton JW, Hanson JS, Hardi R, Hemaidan A, Higgins P, Holderman W, Hornbuckle K, Ibegbu E, Isaacs KL, Katz JA, Katz S, Kaufman BP, Kavanaugh AF, Khurana SK, Lashner B, Lawrence S, Hansen RN, Lee S, Leighton JA, Leman BI, Levenson SD, Lowe JE, Marcuard SP, Matsuyama RM, McNair AE, Melmed G, Miller KM, Miner PB Jr, Mutlu EA, Keshavarzian A, Narayen V, Noar MD, Patel PH, Patrick TJ, Peck A, Peterson KA, Phillips RW, Picco MF, Randall C, Richards RJ, Safdi MA, Scherl EH, Schwartz DA, Schwartz HI, Schwartz JL, Sedghi S, Shafran I, Siegel CA, Sninsky CA, Stern M, Suiter D, Swaminath A, Terdiman JP, Mahadevan U, Thomson C, Valentine J, Vasudeva R, Vecchio JA, Wolf DC, Yajnik V, Yabkowski J, Yen E.

Author information

1
Division of Gastroenterology, University of California San Diego, La Jolla, California 92093-0956, USA. wsandborn@ucsd.edu

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.).

PMID:
23075178
DOI:
10.1056/NEJMoa1203572
[Indexed for MEDLINE]
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