medwireNews: Patients with Crohn’s disease who do not initially respond to 12 weeks of induction therapy with the antibody risankizumab may see improvements in the disease after continuing treatment for up to a year, researchers say.
After receiving risankizumab 180 mg subcutaneously, 360 mg subcutaneously, or 1200 mg intravenously for an additional 12 weeks, the majority of patients who did not initially respond to the treatment had a clinical response, with rates of 76.2%, 63.7%, and 62.3%, respectively. A clinical response was defined as a 30% or greater decrease in average daily stool frequency and/or the same reduction on the average daily abdominal pain score (ranging from 0 points for none to 3 points for severe pain), with neither measure worse than baseline.
The investigators also found that 43.0%, 45.1%, and 22.1% of patients in the respective treatment groups achieved clinical remission by week 24, defined as an average daily stool frequency of 2.8 or less, and an average daily abdominal pain score of 1 point or less, with neither measure worse than baseline.
While standard advanced therapy induction regimens are typically 12 weeks or less in Crohn's disease, some patients may benefit from alternative treatment strategies, say Remo Panaccione (University of Calgary, Alberta, Canada) and colleagues in Clinical Gastroenterology and Hepatology.
“With limited advanced treatment options available for patients with moderate to severe CD, optimizing their use to maximize benefit and delay disease progression is of paramount importance,” they write.
The researchers analyzed clinical outcomes for patients with moderate-to-severe Crohn's disease who had shown no clinical response to 12 weeks of intravenous risankizumab (600 mg or 1200 mg at weeks 0, 4, and 8) in the ADVANCE and MOTIVATE phase 3 induction trials. Of these 313 nonresponders, 252 were then re-assigned to receive subcutaneous risankizumab 180 mg (n=84) or 360 mg (n=91) on weeks 12 and 20 or intravenous risankizumab 1200 mg at weeks 12, 16, and 20 (n=77).
At baseline, 54.8% of the patients were men, the mean age across the treatment groups was 37.8–40.6 years, and the average Crohn's disease duration ranged from 10.3–12.1 years. The participants had a mean average daily stool frequency of 5.4–6.2, and mean scores of 1.7–1.9 points on the average daily abdominal pain measure.
The patients also scored a mean of 303.9–312.1 out of a possible 600 points on the Crohn’s Disease Activity Index (CDAI) at baseline, where a higher result indicates more severe disease. And the mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) scores were 13.5–14.7 points out of 56 points, with higher scores indicating more severe disease.
Panaccione et al report that endoscopic responses at week 24, defined as a 50% or greater decrease in SES-CD score, were achieved by 32.4% of the risankizumab 180 mg subcutaneous group, 32.5% of the 360 mg subcutaneous group, and 40.5% of the intravenous 1200 mg group. They also note that a respective 25.1%, 18.0%, and 23.5% of patients achieved endoscopic remission, defined as an SES-CD score of 4 points or less, with no subscore above 1 point.
At the same time, a CDAI clinical response, defined as a decrease of 100 points or more from baseline, was achieved by a corresponding 54.3%, 59.3% and 40.3% of patients, and 43.0%, 45.1%, and 22.1% achieved CDAI clinical remission, defined as a decrease in CDAI of more than 150 points.
Commenting that the efficacy of achieving endoscopic outcomes after extended treatment was generally similar with intravenous and subcutaneous risankizumab dosing, the authors say that “[t]hese findings, therefore, suggest that ‘reinduction’ with additional [risankizumab intravenous] dosing is not more effective than starting [subcutaneous] dosing for delayed responders.”
Among those patients receiving subcutaneous risankizumab 180 mg and 360 mg who achieved a clinical response by week 24 and continued maintenance treatment within the FORTIFY trial, 56.7% and 69.7%, respectively, maintained a clinical response at week 52. Endoscopic response rates at week 52 were a corresponding 36.7% and 45.5%, while endoscopic remission was observed in 40.0% and 42.4% of the two groups.
Panaccione and colleagues also found that no new safety concerns emerged at week 24 or week 52, with the most frequently reported adverse events of special interest including hypersensitivity and mild injection site reactions. There was one reported death due to sepsis in a patient with a history of fistulizing Crohn's disease, but the event was determined to be unrelated to the study drug.
“Despite the difficult-to-treat nature of this population, a robust response to continued treatment was demonstrated,” the investigators write.
They conclude that extending risankizumab therapy was “beneficial for most patients with moderate to severe CD who did not achieve clinical response” to a standard 12-week induction, and therefore for patients with this pattern of disease, “starting [risankizumab] maintenance treatment would provide the greatest opportunity for benefit.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group
Clin Gastroenterol Hepatol 2025; doi:10.1016/j.cgh.2024.12.023