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PHILADELPHIA -- Significantly more patients with moderate-to-severe ulcerative colitis (UC) given a single dose of ustekinumab (Stelara) achieved clinical remission compared with those given placebo, an investigator reported here.

At week 8, 15.6% of patients receiving one intravenous 130-mg dose of ustekinumab were in clinical remission, as were 15.5% of those given the interleukin 12/23 blocker in doses of approximately 6 mg/kg, according to Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai Hospital in New York City.

In contrast, only 5.3% of patients randomized to placebo achieved clinical remission by week 8 (P<0.001), he reported in a late-breaking session at the American College of Gastroenterology annual meeting.

"Ulcerative colitis is a complex immune disease, and more than half of UC patients have not experienced remission with currently available conventional or biologic treatment options," Sands said.

The phase III study, known as , included 961 patients with moderate-to-severe ulcerative colitis. Half had prior biologic failure, with 17% having had an inadequate response or intolerance to an anti-tumor necrosis factor agent or vedolizumab (Entyvio). "This was a fairly refractory group of patients," he told 名媛直播. The drug seemed to have the same treatment effect size of about 10% in both prior biologic failures and non-biologic failures, he noted.

Remission was defined as a Mayo score of ≤2 points, with no individual subscore >1.

Patients' mean age was 41, and mean disease duration was 6 years. The median Mayo score was 9, and 15% had severe disease, with Mayo scores >10.

Endoscopic healing, defined as a Mayo endoscopy subscore of 0 or 1, was seen in 26.3% of patients given the 130-mg dose and in 27% of those given the weight-based dose of 6 mg/kg, compared with 13.8% of those receiving placebo (P<0.001).

Another secondary endpoint was clinical response, which was defined as a decrease from baseline of at least 30% and at least 3 points on the Mayo score, plus a rectal bleeding subscore decrease from baseline of at least 1 point or a subscore of 0 or 1. This outcome was achieved by 51.3% of the 130-mg group and 61.8% of the 6 mg/kg group, compared with 31.3% of the placebo group (P<0.001).

An additional novel endpoint was mucosal healing, defined as endoscopic healing plus histologic healing, which required <5% neutrophils in the epithelium, no erosions, ulcerations, or granulations, and no crypt destruction. This was achieved by 20.3% and 18.4% of the two ustekinumab groups, respectively, compared with 8.9% of the placebo group (P<0.001).

The ustekinumab-treated patients also had significant improvements in health-related quality of life as measured on the Inflammatory Bowel Disease Questionnaire, and in inflammatory markers such as C-reactive protein and fecal lactoferrin.

Adverse events were similar in the three groups, with no malignancies or opportunistic infections being reported during the 8 weeks of the study. One patient in the 6 mg/kg died of esophageal variceal bleeding thought to be unrelated to the treatment.

The study is continuing, with a 44-week maintenance phase.

Ustekinumab is already approved for Crohn's disease, "where it works pretty well," Sands said. "The efficacy seems very consistent with what's been seen with Crohn's. In broad terms, it seems consistent with what's seen with vedolizumab and with tofacitinib [Xeljanz], so it gives us another option for the treatment of patients with ulcerative colitis."

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