A Randomized Trial of Ustekinumab, a Human interleukin-12/23 Monoclonal Antibody, in Patients With Moderate-To-Severe Crohn's Disease

Gastroenterology. 2008 Oct;135(4):1130-41. doi: 10.1053/j.gastro.2008.07.014. Epub 2008 Jul 17.

Abstract

Background & aims: Interleukin-12 and interleukin-23 are inflammatory cytokines implicated in Crohn's disease pathophysiology. Ustekinumab is a monoclonal antibody against the p40 subunit of interleukin-12/23.

Methods: We performed a double-blind, cross-over trial of the clinical effects of ustekinumab in 104 patients with moderate-to-severe Crohn's disease (population 1). Patients were given subcutaneous placebo at weeks 0-3, then ustekinumab at weeks 8-11; subcutaneous ustekinumab at weeks 0-3, then placebo at weeks 8-11; intravenous placebo at week 0, then ustekinumab at week 8; or intravenous ustekinumab at week 0, then placebo at week 8. Furthermore, an open-label trial evaluated the effects of 4 weekly subcutaneous injections or 1 intravenous infusion of ustekinumab in 27 patients who were primary or secondary nonresponders to infliximab (population 2).

Results: In population 1, clinical response rates for the combined groups given ustekinumab and placebo were 53% and 30% (P = .02), respectively at weeks 4 and 6, and 49% and 40% (P = .34), respectively at week 8. In a subgroup of 49 patients who were previously given infliximab (neither primary nor secondary nonresponders), clinical response to ustekinumab was significantly greater than the group given placebo (P < .05) through week 8. In population 2, the clinical responses at week 8 to subcutaneous and intravenous ustekinumab were 43% and 54%, respectively. There was no increase in the number of adverse or serious adverse events in patients given ustekinumab through week 8 compared with placebo.

Conclusions: Ustekinumab induced a clinical response in patients with moderate-to-severe Crohn's disease, especially in patients previously given infliximab.

Trial registration: ClinicalTrials.gov NCT00265122.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology*
  • Cross-Over Studies
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / immunology
  • Interleukin-23 / antagonists & inhibitors*
  • Interleukin-23 / immunology
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome
  • Ustekinumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Interleukin-23
  • Interleukin-12
  • Ustekinumab

Associated data

  • ClinicalTrials.gov/NCT00265122