Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease
Laurent Peyrin-Biroulet1, J Casey Chapman1, Jean-Frederic Colombel1
1From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.).
Background:
The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown.
Methods:
In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab.
Results:
In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups.
Conclusions:
In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).
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