Potential new drug for Crohn's Disease

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

Abstract 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.

Viewpoint Ustekinumab seems an exciting new potential drug to be used in people with Crohn’s Disease. Previously, the antibody treatments have focused on having an effect of neutralising tumour necrosis factor. This new agent seems to be promising for patients with Crohn disease who are do not respond to anti-TNF agents. This drug has an effect on a completely new arm of the immune system that appears to be dysregulated in Crohn's disease. Longer term follow-up will be needed to determine the durability of effect and safety. CMH

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