Re-defining outcomes and re-evaluating remission in inflammatory bowel disease: Assessing key evidence

摘要

Introduction The term inflammatory bowel disease (IBD) encompasses two conditions: Crohn’s disease (CD) and ulcerative colitis (UC) (Abreu and Sparrow 2006). The term UC dates from 1888 (Baron 2000) and Burrill Crohn described the eponymous condition in 1932 (Crohn et al 1932). Since the mid 1950s when it was first reported that oral cortisone induced clinical remission in UC (Truelove and Witts 1955), corticosteroids have since become a mainstay of IBD management. Yet approximately 16% of patients do not respond to these agents (Faubion et al 2001) and the side effects and serious adverse reactions associated with their use are well known (Yang and Lichtenstein 2002). By 1980, researchers had isolated 5-aminosalicylate (5-ASA) as the moiety responsible for the activity of sulfasalazine in IBD (Azad Khan et al 1977; van Hees et al 1980). The immunosuppressant thiopurines are also widely used, despite the fact that they can take up to a median of 3 months to reach optimum efficacy (Lémann et al 2006). It is in part because of the limitations associated with corticosteroids and immunosuppressant drugs that 50%–80% of people with CD ultimately require surgical interventions to treat the condition (National Institute for Health and Clinical Excellence [NICE] 2002); almost 10% of UC patients require colectomy in the year of diagnosis (Faubion et al 2001). Furthermore, mucosal inflammation seems to persist even during symptomatic remission induced by non-biological agents. This sub-clinical mucosal inflammation appears to be associated with the risk of clinical relapse (Arnott et al 2001, 2002). In contrast, some biological agents that target tumor necrosis factor alpha (TNF-α) appear to heal the gastrointestinal mucosa in patients with IBD, as demonstrated in studies involving the anti-TNF-α agent infliximab. This healing is associated with improved signs and symptoms, long-term maintenance of remission, and a reduction in the risk of complications, surgery and hospitalization in CD and UC (Rutgeerts et al 2002, 2007). Although further studies are needed to determine whether mucosal healing is a feature of the other biological agents, it is plausible to pose the hypothesis that mucosal healing, as it appears to correlate with quiescent IBD, could offer a clinically useful marker indicating a favorable long-term prognosis. Against this background, a group consisting of Professor Laurence J Egan, Chair of Clinical Pharmacology at the National University of Ireland, Dr Simon M Everett, Consultant Gastroenterologist at the University of Leeds, UK and Professor Paul Rutgeerts, Professor of Medicine, Division of Gastroenterology, at the University of Leuven in Belgium, came together to examine whether the treatment goals and management of IBD should change to reflect the evolving evidence base. This supplement is based on these discussions, which primarily focused on evidence for CD. As more studies have been carried out on the use of infliximab in IBD than the other biological agents, some discussions focused on data from the infliximab evidence base to illustrate their points. The authors hope that the supplement will stimulate debate and discussion about whether the outcome measures and pharmacological management of IBD should now be revised.