Risankizumab Shows Efficacy in Treating Pouch Complications

Among a highly refractory cohort of patients with ulcerative colitis who developed Crohn’s disease of the pouch (CDP) following ileal pouch-anal anastomosis surgery, risankizumab achieved the primary outcome of clinical remission in 50% and the more stringent secondary outcome of antibiotic- and steroid-free remission in 30.8%, investigators reported in Inflammatory Bowel Disease.

Furthermore, among patients previously treated with ustekinumab for CDP, risankizumab achieved clinical and antibiotic- and steroid-free remission in a nearly identical proportion of patients (43.8%).

“Approximately 10% to 15% of patients develop after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) for medically refractory ulcerative colitis (UC),” the authors wrote.  

CDP is characterized by proximal small bowel inflammation, strictures, and fistulae, and conveys a significant risk of pouch failure. For the purposes of this study, CDP was prespecified as prepouch ileitis, strictures of the pouch body or prepouch ileum, and/or fistulae that occurred greater than 6 months after IPAA.

Because most patients with CDP have been exposed to several biologic therapies with no success or loss of response prior to proctocolectomy, there is a significant need for new therapeutic options for patients with CDP.

Investigators conducted a prospective analysis of patients treated with risankizumab who were included in the multicenter Prospective Registry for the Study of Outcomes and Predictors of Pouchitis and Pouch-Related Disorders (PROP-RD) between July 2022 and November 2023. Lab values were recorded when patients received the initial infusion of risankizumab.

“The primary outcome was clinical remission defined as a clinical Pouchitis Disease Activity Index (PDAI) subscore <2 at 12 weeks,” the authors explained. “The secondary outcomes were combined steroid- and antibiotic-free clinical remission at 12 weeks, clinical remission at 24 weeks, and endoscopic remission at 24 weeks defined as an endoscopic PDAI subscore <2.”

The analysis identified 26 patients with CDP and a median pouch duration of 15.0 years; 15 (57.7%) were women. Before risankizumab induction, 21 (80.8%) patients had received biologics and/or small molecules for CDP, and 16 (61.5%) had previously been treated with ustekinumab. The median number of advanced therapies prescribed for CDP prior to risankizumab induction was 3.

“At baseline, the median clinical PDAI subscore was 3 (IQR, 2-4), and the median values of C-reactive protein (CRP) and calprotectin were 8 mg/L (IQR, 2.6-14.9) and 322 mcg/g (IQR, 199-399.3), respectively. Ten (38.5%) and 4 (15.4%) patients were on antibiotics and/or budesonide at baseline, respectively.”

At 12 weeks, 13 of 26 (50%) patients achieved the primary outcome of clinical remission; 8 of 26 (30.8%) patients achieved the secondary outcome of combined steroid- and antibiotic-free clinical remission. Of 14 patients on antibiotics and/or budesonide at baseline, 3 (21.4%) were able to discontinue either agent at 12 weeks.

Among the 16 patients who had previously been treated with ustekinumab, 7 (43.8%) achieved clinical remission and combined steroid- and antibiotic-free clinical remission. “There was no significant difference in clinical remission rates stratified by previous ustekinumab exposure (P = .42),” the authors noted. “Over the 12-week induction period, the median decrease in the clinical PDAI subscore was 1 (IQR, 0-2; Figure 1), and the median decrease in CRP was 4 (IQR, 0.7-12.0).” At 24 weeks, the secondary outcome of clinical remission was achieved in 18 of 26 (69.2%) patients.

Of the 13 patients who did not achieve remission at 12 weeks, more than half (57.1%) did achieved clinical remission at 24 weeks. Among 13 patients who achieved remission at 12 weeks, all but 1 (92.3%) remained in clinical remission at 24 weeks.

“Among the 13 patients with a follow-up pouchoscopy at least 24 weeks after induction, the median endoscopic PDAI subscore was 0 (IQR, 0-2), and the median decrease in the endoscopic PDAI subscore compared with baseline was 2 (IQR, 0-2). Endoscopic remission was achieved in 9 (69.2%) patients,” the authors wrote. “The concordance rate between endoscopic and clinical remission was 76.9%. Of the 6 patients with fistulae and the 9 patients with strictures at baseline, 5 (83.3%) and 6 (66.7%) achieved fistula healing and stricture resolution at 24 weeks, respectively.”

There were no drug-related adverse events. Two patients discontinued risankizumab following 24 and 28 weeks of therapy, due to primary nonresponse.

Reference:

Kayal M, Spencer EA, Smyth M, et al. Risankizumab is effective for the management of Crohn’s disease of the pouch. Inflamm Bowel Dis. 2025;31, 878–881 https://doi.org/10.1093/ibd/izae164.