Evidence-Based Medications for the Treatment of the Inflammatory Bowel Diseases

Sarah A. De La Rue; Stephen J. Bickston

Disclosures

Curr Opin Gastroenterol. 2006;22(4):365-369. 

In This Article

Ulcerative Colitis

The year has also brought substantial progress in the available treatments for ulcerative colitis.

The use of formulations of 5-ASA for the treatment of ulcerative colitis, including both sulfasalazine and many more recent formulations, is far better supported than their use in Crohn's disease. In general, the data indicate that the therapeutic efficacy is dose dependent. This is further supported by a recent trial of Asacol (Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, USA), a formulation of mesalamine coated with a polymer that limits drug release until it reaches the colon.[21*] The authors compared 2.4 g/day versus 4.8 g/day in 268 patients. They found that administration of 4.8 g/day significantly improved the likelihood that patients with moderately active ulcerative colitis would achieve overall improvement at 6 weeks compared with patients administered 2.4 g/day.[21*]

Conventional thinking maintains that there is no benefit to treating asymptomatic patients. This is contradicted, however, by data for patients with ulcerative colitis, for whom higher inflammatory scores on biopsy appear to translate into increased risk of dysplasia and cancer.[22] On the other hand, preparations of 5-ASA seem to confer a decreased risk. A British group examined the records of 18 969 patients, of whom 100 had developed colorectal cancer during 5-ASA exposure.[23*] The majority of the patients who were examined had a history of ulcerative colitis. They found that patients who were regular users of mesalamine preparations or sulfasalazine, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of colorectal cancer than irregular users.

The data on these agents originally suffered from poor study design, limits on generalizability and commercial bias: true 'junk science'. Reviews mentioning them still grossly outnumber studies with primary data, but the application of better study design supports their use. Thus far, there are more data for probiotic use in ulcerative colitis than in Crohn's disease. VSL#3 is a combination of probiotic strains that has been shown to maintain remission and decrease the incidence of pouchitis. Recent open-label data suggest that it may have utility for the induction of remission in patients with ulcerative colitis.[24] In this small study of 34 patients with moderately active ulcerative colitis, there was a 77% response rate, indicating that the VSL#3 probiotic mixture induces remission in patients with active ulcerative colitis. A German study[25] found equivalent efficacy of Escherichia coli Nissle 1917 and mesalazine in maintaining remission in ulcerative colitis. Although interesting, these must be considered grade III data and require more extensive exploration and validation in large-scale clinical trials.

Infliximab has been used off-label for the treatment of ulcerative colitis for several years, but evidence-based medicine now puts both clinicians and third party payers on firmer ground. Rutgeerts et al.[26**] showed that the regimen of infliximab used for Crohn's disease could be applied successfully to patients with moderate to severe ulcerative colitis. Of the patients who received 5 and 10 mg infliximab, a clinical response was seen at week 8 in 69% and 61%, respectively, as compared with 37% of those who received placebo (P < 0.001 for both comparisons with placebo). The clinical trials described by these authors (Active Ulcerative Colitis Trial (ACT) I and ACT II) employed Mayo scores, which is a combined system of endoscopic scoring and clinical manifestations; this may represent a frameshift in clinical study design for ulcerative colitis.[26**]

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