Top 10 Practice-Changing Articles of 2012: Gastroenterology

David A. Johnson, MD


January 16, 2013

In This Article

Ustekinumab Induction and Maintenance Therapy in Refractory Crohn's Disease

Sandborn WJ, Gasink C, Gao LL, et al
N Engl J Med. 2012;367:1519-28


Study Summary

Ustekinumab is an all-human, monoclonal antibody that blocks activity of the common Tp40 subunit of interleuken-12 and interleuken-23 cytokines on T cells, natural killer cells, and antigen-presenting cells. It is approved for treatment of moderate-to-severe plaque psoriasis. This was a phase 2b, randomized, placebo-controlled, dose-ranging study involving 526 patients with a Crohn Disease Activity Index (CDAI) score of 220-450 points and previous nonresponse to tissue-necrosis factor (TNF) antagonists. Active induction therapy involved 1, 3, or 6 mg/kg of intravenous ustekinumab or placebo for 8 weeks. Patients who responded to ustekinumab and those who did not were randomly assigned separately to receive subcutaneous maintenance therapy with ustekinumab or placebo at weeks 8 and 16, with efficacy of maintenance assessed at week 22. The primary endpoint was clinical response (a decrease of >100 points from baseline CDAI) at week 6, and the secondary endpoint was clinical remission (CDAI score of <150) at weeks 6 and 22.

The clinical response at week 6 was superior with ustekinumab (6 mg/kg) vs placebo (39.7% vs 23.5%; P = .005), as well as response at week 22 (69.4% vs 42.5%; P < .001) and clinical remission at week 22 (41.7% vs 27.4%; P = .03). The percentage of patients in clinical remission at week 6 who maintained remission at week 22 was numerically but not statistically higher with ustekinumab than with placebo (78.6% and 53.5%; P = .06). Safety outcomes, assessed through week 36, were good, consisting of a few infections that are typical in patients with Crohn disease and no atypical infections.


Ustekinumab seems to be promising for patients with Crohn disease that is refractory to anti-TNF agents. Longer term follow-up will be needed to determine the durability of effect and safety.