A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease.

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.

• Authors: William J Sandborn, Brian G Feagan, Richard N Fedorak, Ellen Scherl, Mark R Fleisher, Seymour Katz, Jewel Johanns, Marion Blank, Paul Rutgeerts, Ustekinumab Crohn's Disease Study Group
• Journal: Gastroenterology (Gastroenterology) Vol. 135 Issue 4 Pg. 1130-41 (Oct 2008) ISSN: 1528-0012 [Electronic] United States
• PMID: 18706417 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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