Clinical trials in luminal Crohn's disease: a historical perspective.
It goes back to 1932 when Dr. Burrill Bernard Crohn and co-workers published their landmark paper, describing regional ileitis as a disease entity. However, clinical trial research has been developing rather slowly in luminal Crohn's disease. It took until the early seventies before the first randomized clinical trial was set up by the National Co-operative Crohn's Disease Study (NCCDS) group. Although the efforts of this group triggered a first wave of clinical trials in Crohn's disease, the lack of guidelines for conducting a clinical trial in this research area resulted in a variety of study designs and much criticism. Besides having a rather small sample size and a short follow-up time, they were often characterized by vague and subjective assessment of disease activity and treatment response. Following the advent of a new and very potent drug class in the late nineties, the anti-TNF agents, investigators started to re-think their study protocols and the first guidelines were set up by the regulatory authorities. Over the last 15years, clinical trials in luminal Crohn's disease have been evolving significantly. Inclusion criteria have been shifting from clinical scores such as Crohn's Disease Activity Index (CDAI) to more objective disease activity parameters such as biomarkers (C-reactive protein and faecal calprotectin) and endoscopic lesions. Primary endpoints have been developing from clinical response to corticosteroid-free remission and more ambitious end-points such as mucosal healing. In this paper, we will give a historical overview on clinical trials in luminal Crohn's disease, before and within the biologic era, and provide insight into how they have shaped our current understanding of trial designs in Crohn's disease.
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
IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.
Alessandro
A
Armuzzi
Department of Gastroenterology, Hospital Clinic, IDIBAPS, CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Julian
J
Panès
Inserm U 954 and Department of Hepato-Gastroenterology, University Hospital of Nancy-Brabois, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
Laurent
L
Peyrin-Biroulet
D003424:Crohn Disease / Q000188:drug therapy* / Q000266:history; D017408:Guidelines as Topic; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018579:Patient Selection; D010919:Placebos / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000266:history* / Q000592:standards; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007166:Immunosuppressive Agents; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha
Biologicals; Clinical trials; Crohn's disease; Mucosal healing; Placebo