A Randomized Trial of Ustekinumab, a Human Interleukin-12/23 Monoclonal Antibody, in Patients With Moderate to Severe Crohn's Disease.
Gastroenterology. 2008 Jul 17. [Epub ahead of print]
Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J, Blank M, Rutgeerts P; for the Ustekinumab Crohn's Disease Study Group.
Mayo Clinic, Rochester, Minnesota.
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 were 53% and 30% (P = .02) at weeks 4 and 6, respectively, and 49% and 40% (P = .34) at week 8. In a subgroup of 49 patients who were previously given infliximab (neither primary nor secondary nonresponders), the clinical response to ustekinumab was significantly greater than the group given the placebo (P < .05) through week 8. In population 2 (n = 27), 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. |
