Clinical trials in ulcerative colitis: a historical perspective.
The clinical trial landscape in ulcerative colitis has evolved significantly in recent decades. Study endpoints have been shifting from mere clinical response to mucosal healing. It has become clear that the choice of combined clinical and endoscopic outcome criteria leads to a reduction in placebo responses, especially when central reading of the endoscopic images is performed. Accumulating evidence suggests that histological remission yields better long-term outcomes for ulcerative colitis patients than mucosal healing alone, and clinical trials with prolonged follow-up will have to address whether histological remission should be the ultimate treatment goal in ulcerative colitis. In recent years there has also been increasing interest in the implementation of patient-reported outcomes in clinical practice and research, and the regulatory authorities have set up guidelines for the development of such outcomes. This paper aims to provide a comprehensive review of historical aspects of clinical trials in ulcerative colitis and to discuss challenges and perspectives for clinical trials in the near future. A thorough analysis of all available landmark literature (both original papers and reviews) on clinical trials in ulcerative colitis was performed.
Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
Pieter
P
Hindryckx
Department of Gastroenterology, AZ Delta, Roeselare, Belgium.
Filip
F
Baert
IBD Unit, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Ailsa
A
Hart
Department of Pharmacology and Therapeutics, Division of Gastroenterology, Hospital de Sao Joao, University of Porto, Porto, Portugal.
Fernando
F
Magro
IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.
Alessandro
A
Armuzzi
Inserm U 954 and Department of Hepato-Gastroenterology, University Hospital of Nancy-Brabois, Université de Lorraine, Vandoeuvre-lès-Nancy, France peyrinbiroulet@gmail.com.
Laurent
L
Peyrin-Biroulet
D001688:Biological Products / Q000266:history*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000266:history* / Q000473:pathology; D003113:Colonoscopy; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D060046:Maintenance Chemotherapy / Q000266:history*; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000266:history*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha
Ulcerative colitis; clinical trials; histological healing; history; mucosal healing