Ustekinumab as induction and maintenance therapy for Crohn's disease

UNITI-IM-UNITI Study Group

Research output: Contribution to journalArticle

341 Citations (Scopus)

Abstract

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin- 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.

Original languageEnglish (US)
Pages (from-to)1946-1960
Number of pages15
JournalNew England Journal of Medicine
Volume375
Issue number20
DOIs
StatePublished - Nov 17 2016

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Crohn Disease
Placebos
Therapeutics
Maintenance
Interleukin-12 Subunit p40
Ustekinumab
Subcutaneous Injections
Tumor Necrosis Factor-alpha
Monoclonal Antibodies
Body Weight
Population

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

UNITI-IM-UNITI Study Group. / Ustekinumab as induction and maintenance therapy for Crohn's disease. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 20. pp. 1946-1960.
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title = "Ustekinumab as induction and maintenance therapy for Crohn's disease",
abstract = "BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin- 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.",
author = "{UNITI-IM-UNITI Study Group} and Feagan, {Brian G.} and Sandborn, {William J.} and Christopher Gasink and Douglas Jacobstein and Yinghua Lang and Friedman, {Joshua R.} and Blank, {Marion A.} and Jewel Johanns and Gao, {Long Long} and Ye Miao and Adedokun, {Omoniyi J.} and Sands, {Bruce E.} and Hanauer, {Stephen B.} and Severine Vermeire and Stephan Targan and Subrata Ghosh and {De Villiers}, {Willem J.} and Colombel, {Jean Frederic} and Zsolt Tulassay and Ursula Seidler and Salzberg, {Bruce A.} and Pierre Desreumaux and Lee, {Scott D.} and Loftus, {Edward V.} and Dieleman, {Levinus A.} and Seymour Katz and Paul Rutgeerts and P. Bampton and A. Chung and S. Connor and H. Debinski and R. Leong and F. Macrae and P. Pavli and D. Sorrentino and {van den Bogaerde}, J. and W. Vogel and H. Vogelsang and E. Louis and F. Mana and C. Zaltman and G. Aumais and C. Bernstein and B. Bressler and S. Dhalla and J. Marshall and R. Panaccione and M. Ropeleski and J. Stehlik and Razvan Arsenescu",
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Ustekinumab as induction and maintenance therapy for Crohn's disease. / UNITI-IM-UNITI Study Group.

In: New England Journal of Medicine, Vol. 375, No. 20, 17.11.2016, p. 1946-1960.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ustekinumab as induction and maintenance therapy for Crohn's disease

AU - UNITI-IM-UNITI Study Group

AU - Feagan, Brian G.

AU - Sandborn, William J.

AU - Gasink, Christopher

AU - Jacobstein, Douglas

AU - Lang, Yinghua

AU - Friedman, Joshua R.

AU - Blank, Marion A.

AU - Johanns, Jewel

AU - Gao, Long Long

AU - Miao, Ye

AU - Adedokun, Omoniyi J.

AU - Sands, Bruce E.

AU - Hanauer, Stephen B.

AU - Vermeire, Severine

AU - Targan, Stephan

AU - Ghosh, Subrata

AU - De Villiers, Willem J.

AU - Colombel, Jean Frederic

AU - Tulassay, Zsolt

AU - Seidler, Ursula

AU - Salzberg, Bruce A.

AU - Desreumaux, Pierre

AU - Lee, Scott D.

AU - Loftus, Edward V.

AU - Dieleman, Levinus A.

AU - Katz, Seymour

AU - Rutgeerts, Paul

AU - Bampton, P.

AU - Chung, A.

AU - Connor, S.

AU - Debinski, H.

AU - Leong, R.

AU - Macrae, F.

AU - Pavli, P.

AU - Sorrentino, D.

AU - van den Bogaerde, J.

AU - Vogel, W.

AU - Vogelsang, H.

AU - Louis, E.

AU - Mana, F.

AU - Zaltman, C.

AU - Aumais, G.

AU - Bernstein, C.

AU - Bressler, B.

AU - Dhalla, S.

AU - Marshall, J.

AU - Panaccione, R.

AU - Ropeleski, M.

AU - Stehlik, J.

AU - Arsenescu, Razvan

PY - 2016/11/17

Y1 - 2016/11/17

N2 - BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin- 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.

AB - BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin- 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.

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U2 - 10.1056/NEJMoa1602773

DO - 10.1056/NEJMoa1602773

M3 - Article

VL - 375

SP - 1946

EP - 1960

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 20

ER -