Ustekinumab successfully induces clinical response and remission in patients with refractory Crohn's disease, according to a new phase IIb trial. The research, published in the New England Journal of Medicine, indicates that ustekinumab could be an alternative treatment option once other medications have failed—a serious issue in the treatment of patients with IBD.

Ustekinumab—a human monoclonal antibody against IL-12 and IL-23—is already approved as a therapeutic agent for psoriasis. Preclinical studies have implicated IL-12 and IL-23 in the pathogenesis of Crohn's disease. Indeed, early clinical trial results hinted at the effectiveness of ustekinumab for Crohn's disease, especially in patients who had previously failed anti-TNF therapy. “The previous study also suggested that larger doses of ustekinumab would have greater efficacy,” says author William Sandborn.

The researchers conducted a 36-week, randomized, placebo-controlled, dose-finding study in patients with moderately to severely active Crohn's disease (n = 526). “All of the patients had failed anti-TNF therapy,” explains Sandborn. “Half of the patients had failed two or three anti-TNF agents,” he adds.

In the induction phase, 1, 3 or 6 mg/kg bodyweight doses of intravenous ustekinumab were tested. Then, individuals who had responded to ustekinumab (n = 145) were randomly re-assigned to receive either 90 mg ustekinumab or placebo at weeks 8 and 16.

A significantly higher proportion of patients receiving the 6 mg/kg ustekinumab dose had a clinical response (a ≥100-point reduction in the baseline Crohn's Disease Activity Index score) than those on placebo (39.7% versus 23.5%; P = 0.005). Furthermore, compared with placebo, maintenance therapy with ustekinumab led to markedly increased rates of clinical remission and response at week 22. In terms of safety, no serious opportunistic infections, cardiovascular events or deaths were reported, but one patient on ustekinumab developed basal-cell carcinoma. Larger trials of longer duration are needed to confirm the safety of ustekinumab in this patient population.

“Three phase III trials are now underway: induction trials in patients with moderate to severe Crohn's disease who are either naive to anti-TNF therapy or have previously failed anti-TNF therapy, and a maintenance trial in patients who responded to induction treatment with ustekinumab,” says Sandborn.