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Breaking the therapeutic ceiling in drug development in ulcerative colitis.

Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium. Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA. Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. Electronic address: severine.vermeire@uzleuven.be.

The lancet. Gastroenterology & hepatology. 2021;(7):589-595
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Abstract

Increased knowledge of the intricate pathogenesis of ulcerative colitis has triggered an advance in drug development during the past two decades, resulting in the advent of several biological agents and small-molecule therapies. Although the increase in therapeutic options is positive, remission rates of patients with ulcerative colitis given new therapeutic agents in induction trials remain at a modest 20-30%, seemingly facing a so-called therapeutic ceiling. This therapeutic ceiling requires a critical appraisal and highlights the need for alternative strategies for drug development. In this Review, we objectively itemise the boundaries of therapeutic efficacy in ulcerative colitis, provide possible explanations for the shortcomings of current strategies, and propose solutions to achieve better therapeutic outcomes in ulcerative colitis.

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Publication Type : Review

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