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SAN DIEGO -- Selective blockade of interleukin (IL)-23 was effective for moderate-to-severe active Crohn's disease in a phase II study, a researcher reported here.
At week 12, clinical remission was reached by 24.4% of patients given 200 mg of the monoclonal antibody risankizumab (BI 655066) at weeks 0, 4, and 8 and by 36.6% of those given 600 mg at those time points compared with 15.4% of those receiving placebo (P=0.308 and P=0.025), according to , of Robarts Clinical Trials in London, Ontario, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Selective blockade of interleukin-23 was effective for moderate-to-severe active Crohn's disease in a phase II study.
- Note that adverse events were similar between the risankizumab groups and placebo.
When the two dose groups were combined, the rate of clinical remission was 30.5% (P=0.049 vs placebo), he reported at the annual Digestive Disease Week.
Those response rates of 15.4%, 24.4%, and 30.5% "give a clear sense of dose linearity," Feagan told 麻豆传媒.
"So in terms of causation, you could argue that in a small trial by chance you could have chance results. But you don't see this linearity of dose response. It's very telling that the effect is real," he said in an interview.
In addition, clinical response rates were 36.6% and 41.5% in the 200-mg and 600-mg groups, respectively, compared with 20.5% in the placebo group (P=0.103 and P=0.037), he noted.
Clinical remission was defined as a score below 150 on the Crohn's disease Activity Index (CDAI), and clinical response was a CDAI score below 150 or a decrease from baseline of 100 points or more.
"The IL-23 pathway has been implicated in the pathogenesis of Crohn's disease both genetically and biologically, specifically through targeting the IL-23 p19 subunit," he said.
To assess the efficacy and safety of this agent in patients with Crohn's disease who had not previously responded either to conventional therapies or a tumor necrosis factor (TNF) inhibitor, the investigators enrolled 74 women and 47 men whose mean age was 38.1.
Their mean CDAI at baseline was 306.8, and mean Crohn's disease Endoscopic Index of Severity (CDEIS) was 13.4. Almost 95% of the patients had previously been treated with at least one TNF inhibitor.
Endpoints other than clinical remission and clinical response were endoscopic remission, which was a CDEIS of 4 or lower or 2 or less for patients with initial isolated ileitis; endoscopic response, which is a score of 7 or lower or a 50% reduction from baseline; and deep remission, which was clinical remission plus endoscopic remission.
At week 12, endoscopic remission was achieved by 14.6% of patients in the 200-mg group and by 19.5% of the 600-mg group compared with 2.6% of the placebo group (P=0.56 and P=0.017). Endoscopic response was reached by 26.8% and 36.6% of the 200-mg and 600-mg groups, respectively, compared with 12.8% of the placebo group.
And deep remission was achieved by 2.4% and 12.2% of the 200-mg and 600-mg groups, but by none of the patients receiving placebo (P=1 and P=0.62).
"Deep remission is the toughest endpoint. Symptoms and endoscopy don't necessarily correlate very well in Crohn's disease, so this is showing two independent endpoints together," Feagan said.
Adverse events were similar between the risankizumab groups and placebo, with any event being reported by 78% of the 200-mg group, by 75.6% of the 600-mg group, and by 82.1% of the placebo group. Severe adverse events occurred in 14.6% and 7.3% of the 200-mg and 600-mg groups, respectively, compared with 23.1% of the placebo group.
It's not uncommon to see more serious adverse events in the placebo group in trials of active Crohn's disease, Feagan noted. The type of events are disease related, and "if you're not on active therapy more bad things are going to happen," he said.
Serious adverse events leading to persistent or significant disability occurred in 22% of the 200-mg group and in 7.3% of the 600-mg group, but in 30.8% of the placebo group. Serious adverse events requiring hospitalization were seen in 19.5% of the 200-mg group and 4.9% of the 600-mg group, compared with 25.6% of the placebo group.
It's been shown that blocking IL-12 and 23 together with ustekinumab (Stelara) is effective in Crohn's in a phase III study. "In contrast, this drug only blocks IL-23, and we think there are some potential advantages to that. If you don't have to block a pathway, you're probably best leaving it alone," Feagan said.
"Looking at the effect size with this drug compared with Stelara suggests that it's probably blocking IL-23 that's the key pathways, not IL-12, because we're seeing an effect as good or better than IL 12/23 together," he said.
Disclosures
The study was funded by Boehringer Ingelheim. Some co-authors are company employees.
Feagan disclosed a relevant relationship with Boehringer Ingelheim.
Primary Source
Digestive Disease Week
Feagan B, et al "Efficacy and safety of induction therapy with the selective IL-23 inhibitor BI 655066, in patients with moderate-to-severe Crohn's disease: results of a randomized double-blind placebo-controlled phase II study" DDW 2016; Abstract 812a.