A37 EFFICACY AND SAFETY OF RISANKIZUMAB AS MAINTENANCE THERAPY IN PATIENTS WITH CROHN’S DISEASE: 52 WEEK RESULTS FROM THE PHASE 3 FORTIFY STUDY

Abstract

Introduction: Risankizumab (RZB), an anti-interleukin (IL)-23p19, was well-tolerated and superior to placebo (PBO) in inducing clinical remission and endoscopic response in patients (pts) with moderate-tosevere Crohn'S disease (CD) in the ADVANCE and MOTIVATE phase 3 studies. Here we report results from FORTIFY (NCT03105102), a 52-week (wk) phase 3 double-blind, re-randomized responder withdrawal study, that evaluated the efficacy and safety of continuing RZB as subcutaneous (SC) maintenance therapy versus withdrawal in pts achieving clinical response to 12wk IV RZB induction therapy. Aims & Methods: IV RZB responders were re-randomized 1:1:1 to receive RZB SC 360mg (N = 141), RZB 180mg (N = 157), or PBO (withdrawal from IV RZB; N = 164) every 8wks for 52wks. Coprimary endpoints were clinical remission (per CD Activity Index [CDAI; US protocol] or stool frequency/abdominal pain score [SF/ APS; outside US protocol]) and endoscopic response at wk52. Other clinical and endoscopic endpoints, inflammatory and pharmacodynamic (PD) biomarkers, RZB serum levels, and safety were assessed over time. All endpoints are defined in the Table. Result(s): RZB serum concentrations at FORTIFY Wk0 were similar among PBO and RZB SC groups; pts assigned to PBO in FORTIFY maintained measurable RZB serum concentrations through wk16 due to the long elimination half-life of RZB. IL-22 concentrations for RZB and PBO arms were suppressed at wk0; by wk52, IL-22 concentrations increased with PBO but were still suppressed as compared to baseline of induction, and levels further decreased in the RZB SC arms. Rates of clinical remission (CDAI, SF/APS) and clinical response were similar for RZB and PBO groups through wk24, with rates lower for PBO thereafter (Table). At wk52, clinical remission (CDAI, SF/ APS) and endoscopic response rates were significantly higher with RZB 360mg than PBO (P < 0.01); RZB 180mg was superior to PBO for clinical remission per CDAI and endoscopic response (P < 0.01) (Table). Endoscopic remission and deep remission rates increased over time with 360mg, remained steady with 180mg, and decreased with PBO (Table). Mean fecal calprotectin and C-reactive protein levels decreased with SC RZB, but increased with PBO, over 52wks (Table). Exposure-adjusted event rates (per 100 pts-years) of serious adverse event (AE) were generally similar among groups (360mg, 21.0 E/100PY and 180mg, 19.5 E/100PY vs PBO, 19.3 E/100PY), as were AEs leading to drug discontinuation (4.8 E/100PY and 2.4 E/ 100PY vs 3.7 E/100PY), and serious infections (6.0 E/100PY and 3.0 E/100PY vs 5.0 E/100PY). Conclusion(s): In pts with moderate-to-severe CD, a robust PD effect on the IL-23 pathway after 12wks RZB IV induction was maintained with RZB SC maintenance therapy. The durability of RZB was demonstrated with high rates of efficacy over the 52-wk study. RZB was superior to PBO for achieving clinical remission and endoscopic response at wk52. Results for the more stringent endpoints (endoscopic remission/deep remission) and persistent improvements in inflammatory biomarkers are consistent with a dose response relationship. Continued RZB SC maintenance treatment was generally safe andwell-tolerated.