An Evidence-Based Systematic Review on Medical Therapies for Inflammatory Bowel Disease

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract. Collectively they are termed inflammatory bowel disease (IBD) and it is estimated that 1.5 million Americans (1) suffer from UC and CD. Their etiologies are unknown, although both are thought to arise from a disordered immune response to the gut contents in genetically predisposed individuals (1). The characteristics of the inflammatory response are different, with CD typically causing transmural inflammation and occasionally associated with granulomas, whereas in UC the inflammation is usually confined to the mucosa. Both UC and CD exhibit a relapsing and remitting course and there is a significant, often dramatic, reduction in quality of life during exacerbations of the disease (2). This has an impact on psychological health, with active IBD patients experiencing greater levels of distress and feelings of lack of sense of self-control compared with the normal population and patients with inactive IBD (3,4). Extrapolation from US administrative claims databases suggests that IBD is responsible for 2.3 million physician visits (5), 180,000 hospital admissions (6), and costs $6.3 billion (7) annually. There have been recent guidelines on the management of both UC (8) and CD (9) that direct the clinician on diagnosis and treatment. Approximately 33% of the cost of IBD is due to medical therapy (7), and given the substantial clinical burden and economic cost of IBD it is important to establish the effectiveness of current medical therapies in both UC and CD. Although there have been several systematic reviews on the efficacy of therapy (10,11), this is a rapidly changing field and there is a need for a comprehensive review of the literature. The American College of Gastroenterology IBD Task Force developed a protocol for systematically reviewing the data on currently available therapies for UC and CD, both in inducing remission and in preventing relapse of the disease. Evidence-based statements were then developed and the strength of recommendation for each was graded according to standard criteria. Section 1 Epidemiology of IBD Multiple studies have evaluated the epidemiology of IBD in adults from various geographic regions; most studies are from Western countries, where the incidence of IBD is highest, the existence of comprehensive databases is more common, and identification of adequately sized populations is easier (12). We have reviewed the literature on population estimates of CD and UC incidence over the past 20 years. Where there was more than one study we have taken the study with the largest population, which is most representative of the country. In the case of two studies of similar size we have evaluated the most recent data. We identified 35 studies (13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47) that provided data on incidence of CD and/or UC. In the US estimates of CD, incidence varies between 6 (13) and 8 (14) per 100,000, with a prevalence of 100 (13) to 200 (12) per 100,000. For UC, the incidence in the United States ranges between 9 (14) and 12 (13), with a prevalence of 205 (13) to 240 (12) per 100,000. Incidence estimates for other countries are given in Table 1. Geographical variation suggests that CD has a higher incidence in industrialized countries and higher rates in the West than in the East (Figure 1a). There also appears to be a North–South gradient with a strong correlation between degrees latitude and CD incidence when the Western Hemisphere and Western Europe are evaluated (Figure 2a). This North–South gradient also exists within an individual country, with CD being less common in the southern United States (12) and in the south of France (32). CD also has a high incidence in New Zealand, suggesting that the disease more common the the is from the There be an to CD that is more in a more similar exists for UC (Figure although the North–South gradient is (Figure Incidence of CD and UC variation in incidence rates for inflammatory bowel disease. Incidence rates for Crohn's disease. Incidence rates for ulcerative per in inflammatory bowel disease incidence rates with degrees latitude from the in Crohn's disease incidence in ulcerative colitis incidence has been in incidence over in most countries (Figure although it to have a in the United States and the Incidence rates are also over for UC, although the of is less (Figure rates to have a in the United States This be due to of is more to a in the that to CD. The of this in inflammatory bowel disease incidence rates over Incidence of Crohn's disease over Incidence of ulcerative colitis over of for CD has been although the disease be The diagnosis of UC also most of and then the incidence Western studies that CD is more common in with a of and a on of CD is a an between and CD in the in is a in the West and in the East CD be more common in The incidence of UC h