Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies. - 2025
Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.
[en] [en] BACKGROUND AND AIMS: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).
METHODS: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo. Clinical responders were randomized to subcutaneous risankizumab 180 mg, risankizumab 360 mg, or placebo (risankizumab withdrawal) in the 52-week phase 3 COMMAND maintenance study. This post hoc analysis assessed outcomes by AT-IR status, number, and mechanism of action. AT included biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators.
RESULTS: Efficacy analyses included 472 non-AT-IR and 503 AT-IR patients (induction), and 137 non-AT-IR and 411 AT-IR patients (maintenance). More patients achieved clinical remission per Adapted Mayo score with risankizumab 1200 mg versus placebo at induction week 12 (non-AT-IR, 29.7% versus 8.4%, nominal P < .0001; AT-IR, 11.4% versus 4.3%, nominal P = .0083); consistent with risankizumab 180 mg or risankizumab 360 mg versus placebo (withdrawal) at maintenance week 52 (non-AT-IR, 50.9% or 61.7% versus 31.1%, nominal P = .057 or P = .0033, respectively; AT-IR, 36.6% or 29.5% versus 23.2%, nominal P = .0159 or P = .2334, respectively). Risankizumab had increased efficacy over placebo, regardless of AT-IR number or mechanism of action, with higher efficacy rates for non-AT-IR compared to AT-IR. Safety results in non-AT-IR and AT-IR patients were generally comparable in both induction and maintenance.
CONCLUSIONS: Risankizumab was effective and well tolerated, regardless of prior AT-IR status.
CLINICAL TRIAL REGISTRATION NUMBERS: INSPIRE [NCT03398148], COMMAND [NCT03398135].
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Panaccione, Remo ; Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Colombel, Jean-Frederic; Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
D'Haens, Geert ; Department of Gastroenterology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
Peyrin-Biroulet, Laurent; Department of Gastroenterology, INFINY Institute, INSERM NGERE, CHRU Nancy, Vandœuvre-lès-Nancy, France ; Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France ; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
Dubinsky, Marla; Department of Pediatrics, Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Takeuchi, Ken; Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha, Kashiwa, Chiba, Japan
Rubin, David T ; University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, United States
Kalabic, Jasmina; AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany
Chien, Karen B; AbbVie Inc, North Chicago, IL, United States
Chen, Su; AbbVie Inc, North Chicago, IL, United States
Cheng, Ling; AbbVie Inc, North Chicago, IL, United States
Zhang, Yafei; AbbVie Inc, North Chicago, IL, United States
Duan, W Rachel; AbbVie Inc, North Chicago, IL, United States
Vladea, Ramona; AbbVie Inc, North Chicago, IL, United States
Hecht, Patrick M; AbbVie Inc, North Chicago, IL, United States
Morisset, Pierre; AbbVie Inc, North Chicago, IL, United States
Schreiber, Stefan; Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany
Ferrante, Marc ; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.
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