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Maintenance risankizumab (Skyrizi) at two different subcutaneous doses helped sustain clinical remissions and endoscopic responses for patients with moderate to severe Crohn's disease, the phase III showed.

Among patients who had responded to 12 weeks of intravenous induction risankizumab, 55.4% and 52.2% of those who received a lower or higher maintenance risankizumab dose, respectively, were in Crohn's Disease Activity Index (CDAI) clinical remission at 52 weeks, as compared to 40.9% of those assigned to placebo (P<0.01 for both), reported Marla Dubinsky, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

For clinical remission based on stool frequency/abdominal pain score, only the higher dose of the interleukin (IL)-23 blocker showed a significant improvement over placebo at 52 weeks, at 51.8% compared to 39.6% (P=0.004), she said in a presentation at the virtual meeting.

Endoscopic response rates doubled with maintenance therapy by study end, at 47.1% and 46.5% with the lower and higher doses, respectively, versus 22% with placebo (P<0.001 for both).

Deep and endoscopic remissions continued to increase for patients given the higher maintenance dose of risankizumab, while these more stringent endpoints remained stable for patients receiving the lower dose. Meanwhile, the placebo group saw declines in deep and endoscopic remissions achieved during induction.

"These results are encouraging with regards to the use of risankizumab and the IL-23 p19 class as a new therapeutic option in Crohn's disease," said Dana Lukin, MD, PhD, of Weill Cornell Medicine in New York City, who was not involved in this study.

Risankizumab is currently only FDA approved for moderate-to-severe plaque psoriasis.

FORTIFY enrolled 462 patients from the and induction trials who had responded to intravenous risankizumab. For the current study, patients were randomized 1:1:1 to receive 360 mg or 180 mg of subcutaneous risankizumab, or placebo, every 8 weeks for 1 year. The co-primary endpoints were CDAI clinical remission and endoscopic response at study end.

Mean patient age was 37 to 39, about half were women, and about three-fourths of patients were exposed to a prior biologic, Dubinsky said, which included patients who failed on ustekinumab (Stelara; about 12% to 15% of the study population).

Risankizumab maintenance was generally safe and well tolerated, Dubinsky noted. Between groups, the rates of any adverse event (AE) were 269 per 100 person-years for the 360 mg group, 284 per 100 person-years for the 180 mg group, and 340 per 100 person-years for the placebo group. For serious AEs, these rates were 21, 20, and 19 per 100 person-years, respectively. And for severe AEs, rates were 16, 9, and 21 per 100 person-years.

Dubinsky reported 10 serious infections in the higher-dose risankizumab group versus five in the lower-dose group and eight in the placebo group. Drug continuation due to toxicity occurred in 4.4% of the higher-dose group versus 2.2% of the lower-dose group and 3.2% of the placebo group.

At the start of the study, IL-22 levels in the risankizumab and placebo arms were suppressed. At week 52, IL-22 levels decreased for the patients on risankizumab maintenance, but increased for the placebo group, Dubinsky reported. Similarly, patients on active maintenance experienced declining inflammatory biomarkers (C-reactive protein and fecal calprotectin levels) over the study period, while those on placebo saw increasing levels.

"This drug has a very long half-life, about a month," noted Dubinsky.

Similar remission and response rates were observed among the risankizumab and placebo groups until week 24, but declined thereafter for the placebo patients.

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