Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials

• Published in: JAMA : the journal of the American Medical Association 2024-09, Vol.332 (11), p.881-897
• Main Authors: Louis, Edouard, Schreiber, Stefan, Panaccione, Remo, Bossuyt, Peter, Biedermann, Luc, Colombel, Jean-Frederic, Parkes, Gareth, Peyrin-Biroulet, Laurent, D’Haens, Geert, Hisamatsu, Tadakazu, Siegmund, Britta, Wu, Kaichun, Boland, Brigid S, Melmed, Gil Y, Armuzzi, Alessandro, Levine, Phillip, Kalabic, Jasmina, Chen, Su, Cheng, Ling, Shu, Lei, Duan, W. Rachel, Pivorunas, Valerie, Sanchez Gonzalez, Yuri, D’Cunha, Ronilda, Neimark, Ezequiel, Wallace, Kori, Atreya, Raja, Ferrante, Marc, Loftus, Edward V
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Clinical trials; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - drug therapy; Colon - diagnostic imaging; Colon - drug effects; Colonoscopy; Double-Blind Method; Female; Friability; Humans; Induction Chemotherapy - adverse effects; Induction Chemotherapy - methods; Inflammatory bowel disease; Interleukin-23 Subunit p19 - antagonists & inhibitors; Intestinal Mucosa - diagnostic imaging; Intestinal Mucosa - drug effects; Maintenance; Maintenance Chemotherapy - adverse effects; Maintenance Chemotherapy - methods; Male; Males; Middle Aged; Monoclonal antibodies; Online First; Original Investigation; Patients; Placebos; Remission; Remission (Medicine); Severity of Illness Index; Ulcerative colitis
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2024.12414

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