S87 Risankizumab Maintenance Therapy Is Effective in Patients Achieving CDAI Clinical Response With Induction Therapy: Post Hoc Analysis From FORTIFY

Abstract

Background: Risankizumab specifically inhibits interleukin 23 by binding to its p19 subunit. Primary results from the phase 3 induction and maintenance trials of risankizumab in patients with moderate-to-severe Crohn’s disease demonstrate risankizumab is efficacious and well tolerated. In contrast to the primary FORTIFY maintenance study analysis that evaluated clinical and endoscopic outcomes at week 52 among patients who met criteria for clinical response based on patient-reported outcomes (European Medicines Agency recommendation), this analysis evaluated patients who met the Food and Drug Administration (FDA) recommended criteria for clinical response based on ≥ 100-point reduction in Crohn’s Disease Activity Index (CDAI). Methods: Patients who achieved CDAI clinical response (≥ 100-point reduction from baseline) with 12 weeks of risankizumab intravenous induction therapy and were randomized to receive subcutaneous risankizumab 360 mg, risankizumab 180 mg, or placebo (withdrawal from intravenous risankizumab) every 8 weeks for 52 weeks in FORTIFY (NCT03105102) were evaluated. Assessments at week 52 included the FORTIFY coprimary endpoints of clinical remission (CDAI < 150) and endoscopic response (> 50% decrease in Simple Endoscopic Score for Crohn’s Disease [SES-CD] or ≥ 2-point reduction in SES-CD for patients with isolated ileal disease and baseline SES-CD of 4), other clinical and endoscopic outcomes, and safety. Results were evaluated based on previous inadequate response or intolerance to biologic therapy (with, Bio-IR; without, non-Bio-IR). Results: A total of 382 patients (risankizumab 360 mg, n = 117; risankizumab 180 mg, n = 135; placebo, n = 130) were included in efficacy analyses. At week 52 of maintenance therapy, clinical remission was achieved by 56.8%, 61.5%, and 46.2% of patients in the risankizumab 360 mg, risankizumab 180 mg, and withdrawal/placebo groups, respectively (P < .05 for both risankizumab groups vs placebo). Clinical remission rates were numerically higher for the non-Bio-IR population (non-Bio-IR: 360 mg, 70.6%; 180 mg, 75.0%; placebo, 64.5%. Bio-IR: 360 mg, 51.1%; 180 mg, 55.8%; placebo, 40.4%). Endoscopic response was achieved by 48.5%, 50.4%, and 21.5% of patients in the risankizumab 360 mg, risankizumab 180 mg, and withdrawal/placebo groups, respectively (P < .001 for both risankizumab groups vs placebo). Endoscopic response rates were numerically higher for the non-Bio-IR population (non-Bio-IR: 360 mg, 58.8%; 180 mg, 65.0%; placebo, 22.6%. Bio-IR: 360 mg, 44.3%; 180 mg, 44.2%; placebo, 21.2%). Response rates for more stringent endoscopic endpoints were numerically higher with risankizumab 360 mg than risankizumab 180 mg (ulcer-free endoscopy, 32.6%, 25.2%; endoscopic remission, 41.2%, 32.6%; deep remission, 32.6%, 28.1%) and consistent with a dose-response relationship. Exposure-adjusted rates of adverse events (AEs), serious AEs, and AEs leading to discontinuation were similar across groups. Conclusion(s): Efficacy and safety results among patients who achieved CDAI clinical response with risankizumab induction therapy were generally similar to those observed for the overall FORTIFY population.1 Risankizumab was superior to placebo for achieving clinical remission and endoscopic response at week 52, more stringent endpoints (endoscopic remission/deep remission) were consistent with a dose-response relationship, and risankizumab maintenance treatment was generally well tolerated.