ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active
Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional
therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous
risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics,
corticosteroid use at baseline, and Simple Endoscopic Score for
Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by
Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and
abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete.
FINDINGS: Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either
risankizumab 600 mg (n=373),
risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to
risankizumab 600 mg (n=206),
risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of
risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with
risankizumab 600 mg and 42% (17%, 8-25; 141/339) with
risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and
abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with
risankizumab 600 mg and 41% (19%, 11-27; 139/339) with
risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with
risankizumab 600 mg and 32% (20%, 14-27; 109/339) with
risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with
risankizumab 600 mg and 40% (21%, 12-29; 77/191) with
risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and
abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with
risankizumab 600 mg and 40% (20%, 12-29; 76/191) with
risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with
risankizumab 600 mg and 34% (23%, 15-31; 65/191) with
risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the
risankizumab 1200 mg group [MOTIVATE]). The death in the
risankizumab-treated patient was deemed unrelated to the study drug.
INTERPRETATION: AbbVie.