Twelve additional weeks of subcutaneous risankizumab induction was efficacious and well-tolerated in patients with Crohn's disease following an initial risankizumab 12-week induction dose.
Marla Dubinsky, MD
Nearly a third of patients with moderate to severe Crohn's disease (CD) experienced a response to a second 12-week induction phase of subcutaneous (SC) risankizumab (Skyrizi) after completing 12 weeks of intravenous (IV) risankizumab without experiencing a response, according to findings presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.
"Subcutaneous risankizumab was efficacious and well-tolerated in patients with delayed clinical response to induction," lead author Marla Dubinsky, MD, Icahn School of Medicine, Mount Sinai, NY, said during a presentation of the results. "These findings underscore the additional clinical benefit of initiating maintenance dosing of subcutaneous risankizumab treatment after IV induction, even in patients who were initial non-responders to 12 weeks IV risankizumab induction."
In the study, patients enrolled in the ADVANCE and MOTIVATE studies who did not respond to 12-weeks of IV risankizumab were re-randomized to receive either 12 additional weeks of IV therapy or 1 of 2 SC doses. Of those receiving a 180 mg SC dose (n = 80), there were 30 with a subsequent response. There were 33 responses in patients receiving a 360-mg dose of risankizumab (n = 84). Those who experienced this delayed response were subsequently followed for 52 weeks.
Baseline characteristics were similar between treatment doses in the delayed responders. These patients were more likely to be male (60% and 63.6%, in the 180 mg and 360 mg dose arms, respectively). The mean disease duration was over 10 years in each group, and all patients had failed at least 1 anti-TNF, with a third having failed more than 1. A third were using corticosteroids and disease locations were evenly mixed, with nearly half having ileal-colonic disease.
Clinical Disease Activity Index (CDAI) clinical response was seen in 75.8% of those responding to the 360 mg dose of risankizumab and in 53.3% of those in the 180 mg dose. Enhanced clinical response was experienced by two-thirds (66.7%) of those in the 360 mg arm and for 53.3% of those in the 180 mg group. A CDAI clinical remission, indicated by a CDAI score drop of up to 150 points was experienced by 66.7% and 56.7% of those in the 360 mg and 180 mg arms, respectively. A stool frequency (SF) drop to 2.8 per day or below and abdominal pain score (ABS) of 1 or less was experienced by 54.5% in the 360 mg arm and by 43.3% in the 180 mg arm.
An endoscopic response was experienced by 45.5% of those treated with the 360 mg dose of risankizumab and by 36.7% of those in the 180 mg arm. Ulcer-free endoscopy was experienced by 24.2% and 27.6% of patients in the 360 mg and 180 mg arms, respectively. Endoscopic remission was experienced by 42.4% of those in the 360 mg arm and by 40.0% in the 180 mg arm.
A few composite endpoints were also examined in the delayed responders. Overall, 36.4% of patients treated with the 360 mg dose of risankizumab experienced both a SF/APS remission and an endoscopic response compared with 23.3% in the 180 mg dose. SF/APS remission and endoscopic remission were similar in groups at approximately 30%. CDAI remission and endoscopic response was experienced by 45.5% of patients in the 360 mg arm and by 36.7% in the 180 mg arm. CDAI clinic remission and endoscopic remission were similar in groups, at 40%.
Adverse events (AEs) were less common in the 360 mg dose arm. There were 132 events in the 180 mg arm and 82 in the 360 mg arm. There were 6 serious AEs in the 180 mg group and 4 in the 360 mg arm. There were 2 major adverse cardiovascular events in the 180 mg arm that were non-fatal and occurred in the same patient. Six cases of injection site reaction occurred in the 180 mg arm and 2 were seen in the 360 mg group.
The oral abstract, “52-Weeks Risankizumab Subcutaneous Maintenance Dosing is Efficacious and Well Tolerated in Patients with Moderate to Severe Crohn’s Disease Who Had Delayed Response to 12-Weeks IV Risankizumab Induction,” was presented at ACG 2022.