Efficacy of risankizumab induction and maintenance therapy by baseline Crohn's disease location: Post hoc analysis of the Phase 3 ADVANCE, MOTIVATE, and FORTIFY studies

ABSTRACT

Background and Aim: In patients with Crohn's disease (CD), disease location affects treatment outcomes.1 This post hoc analysis assessed the efficacy of risankizumab (RZB), an interleukin-23 p19 inhibitor, by disease location. Method(s) In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance or inadequate response to conventional and/or biologic therapy (ADVANCE) or to biologic therapy (MOTIVATE) received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving clinical response to IV RZB induction were re-randomized in a maintenance study (FORTIFY, NCT03105102) to receive subcutaneous (SC) RZB or SC PBO (i.e. withdrawal) for 52 weeks. This post hoc analysis included patients who received RZB 600 mg IV in either ADVANCE or MOTIVATE and patients who received RZB 360 mg SC in FORTIFY. Clinical and endoscopic outcomes were evaluated in patient subgroups stratified by CD location at baseline (ileal only, colonic only, ileal-colonic) using nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19. Result(s) At Week 12, significantly greater proportions of patients receiving RZB 600 mg IV achieved the co-primary endpoints of CD Activity Index (CDAI)-based clinical remission and endoscopic response compared with PBO in the colonic only (n = 190) and ileal-colonic (n = 252) subgroups (P < 0.001). At Week 12, statistically higher proportions of RZB-treated patients achieved the composite endpoint of CDAI clinical remission and endoscopic response, as well as endoscopic remission, in the colonic only and ileal-colonic subgroups compared with PBO (P < 0.001). At Week 52, significantly greater proportions of patients receiving RZB 360 mg SC achieved the co-primary endpoints of CDAI clinical remission and endoscopic response, composite CDAI clinical remission and endoscopic response, and endoscopic remission, compared with withdrawal (PBO SC) in the colonic only (n = 59) and ileal-colonic (n = 67) subgroups (P <= 0.05;Fig. 1a-1d). In patients with endoscopic remission after 12 weeks of IV RZB (Week 0 of maintenance), significantly more RZB-treated patients achieved sustained endoscopic remission at Week 52 compared with withdrawal (PBO SC) in the colonic only and ileal-colonic subgroups (P <= 0.01;Fig. 1e). At Weeks 12 and 52, efficacy rates were numerically lower in ileal-only CD relative to colonic-only and ileal-colonic CD. Results for ileal-only CD are limited by the small number of patients in this subgroup (induction, 85;maintenance, 15). Conclusion(s) RZB induction and maintenance therapy was effective in patients with moderately to severely active CD, with greater benefits observed in patients with any colonic involvement.