Long-Term Risankizumab Data Show Durable Crohn’s, Fistula Outcomes

Long-term risankizumab treatment was associated with sustained or improved clinical and endoscopic outcomes across ileal, colonic, and ileocolonic Crohn’s disease (CD), as well as rising rates of no draining fistula over up to 5 years, according to a pair of post hoc analyses of the FORTIFY open-label extension (OLE) presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.^1,2

The analyses, presented by Parambir Dulai, MD, Northwestern Medicine, address 2 gaps in long-term data for the interleukin (IL)-23 p19 inhibitor: outcomes stratified by baseline disease location and outcomes in patients with draining fistulas, a severe phenotype that often requires months or years of treatment to heal.^1,2

Risankizumab Outcomes by Crohn’s Disease Location Through 144 Weeks

The first analysis included 1112 adults with moderately to severely active CD who completed 52 weeks of risankizumab maintenance in the FORTIFY substudies or the phase 2 OLE. In the OLE, 852 patients received subcutaneous risankizumab 180 mg every 8 weeks (ileal, n = 138; colonic, n = 325; ileocolonic, n = 389). Another 260 patients who had received rescue therapy before week 52 continued 360 mg every 8 weeks (ileal, n = 33; colonic, n = 109; ileocolonic, n = 118).¹

Investigators evaluated clinical remission, endoscopic response, endoscopic remission, and ulcer-free endoscopy through 96 or 144 weeks, using both as-observed and modified nonresponder imputation (mNRI) analyses. High rates of clinical and endoscopic remission, including ulcer-free endoscopy, were reported across all locations. In as-observed analyses, most disease activity measures improved over time; stool frequency and abdominal pain score clinical remission improved in colonic and ileocolonic disease and remained stable in ileal disease. Under mNRI, endoscopic response, endoscopic remission, and ulcer-free endoscopy improved in colonic and ileocolonic disease and held steady in ileal disease.¹

No Draining Fistula Rates With Up to 5 Years of Risankizumab

The second analysis examined 73 OLE participants with draining fistulas at induction baseline. Of these, 51 received risankizumab 180 mg and 22, who had previously required rescue therapy, received 360 mg. Absence of draining fistulas was determined by physical examination as no drainage upon gentle compression, and data were analyzed as observed until patients received rescue therapy.²

At OLE week 0 (week 56 of maintenance, excluding induction), 66.7% (34/51) of patients receiving 180 mg and 36.4% (8/22) receiving 360 mg had no draining fistula, for a pooled rate of 57.5%. By OLE week 192 (week 248 overall), those rates reached 84.2% (32/38) and 52.9% (9/17), respectively, with a pooled rate of 74.5% (41/55).²

The 360 mg group consisted of patients who had needed rescue therapy earlier in the program, and the number of evaluable patients in both groups declined over follow-up.²

FORTIFY Background and Long-Term Risankizumab Data

Risankizumab selectively targets the p19 subunit of IL-23. In the phase 3 ADVANCE and MOTIVATE induction trials, intravenous risankizumab 600 mg or 1200 mg at weeks 0, 4, and 8 met all coprimary end points of clinical remission and endoscopic response at week 12 compared with placebo.⁴ In the FORTIFY maintenance withdrawal trial, 542 induction responders were randomized to subcutaneous risankizumab 180 mg, 360 mg, or withdrawal to placebo. At week 52, Crohn’s Disease Activity Index clinical remission occurred in 52% of patients receiving 360 mg vs 41% of those withdrawn, and endoscopic response in 47% vs 22%, with similar adverse event rates across groups.³

Taken together, the 2 analyses extend the FORTIFY maintenance data to nearly 5 years for patients who responded to risankizumab induction, with outcomes generally maintained across ileal, colonic, and ileocolonic disease and in patients with draining fistulas.

References

1. Dulai PS, et al. Efficacy of risankizumab by Crohn’s disease location: results from 144 weeks of the FORTIFY open-label extension study. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; 2026; Nashville, TN.

2. Dulai PS, et al. Risankizumab for fistulizing Crohn’s disease: post hoc analysis of up to 5 years of treatment from the FORTIFY open-label extension. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; 2026; Nashville, TN.

3. Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399(10340):2031-2046. doi:10.1016/S0140-6736(22)00466-4

4. D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015-2030. doi:10.1016/S0140-6736(22)00467-6