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Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

BACKGROUND: It is not clear if starting intravenous proton pump inhibitors (IV PPI) before endoscopic therapy provides additional benefit over starting it afterward in patients with high-risk ulcer stigmata of peptic ulcer disease.METHODS: All patients who received IV pantoprazole bolus and infusion and underwent endoscopy in six Canadian hospitals over 20 months were reviewed. Only patients with high-risk ulcer stigmata (arterial bleeding, oozing, nonbleeding visible vessel or adherent clot) were included. Patients receiving IV PPI before endoscopy (before group) were compared with those who received it after endoscopy (after group) with respect to endoscopic findings and, secondarily, to patient demographics and clinical outcomes.RESULTS: The demographics and baseline characteristics of the before group (n=57) and the after group (n=109) were similar. The before group was more likely to have had IV PPI started outside of daytime hours, and median time to endoscopy in patients admitted with upper gastrointestinal bleeding was 24 h (interquartile range 9.5 to 35) in the before group and 11.3 h (interquartile range 3.7 to 17.2) in the after group ( P<0.0001). At the time of endoscopy, 33% of patients in the before group had actively bleeding lesions (Forrest 1a or 1b) compared with 54% in the after group (P=0.01), but there were no significant differences in rebleeding, surgical rates, intensive care unit admission or death between the groups.CONCLUSION: IV PPI infusions before endoscopy may lower the proportion of actively bleeding peptic ulcer lesions at endoscopy, but this finding does not appear to affect rates of rebleeding, surgery or death.