IBD Watch^®

^{Timely Information for Practicing Physicians}

 JULY 2006

CROHN'S DISEASE (CD)

Long-term safety data for patients treated with infliximab. Concern exists that infliximab-induced rapid healing in CD increases the risk of development of intestinal stenosis, stricture, and obstruction (SSO). These theoretical complications of infliximab therapy led Lichtenstein and colleagues to analyze data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT) registry and A Crohn's Disease Clinical Trial Evaluating Infliximab in a Long-Term Treatment Regimen (ACCENT I) study. The TREAT data revealed that SSO occurred at a higher rate in patients treated with infliximab than in patients treated with other therapies (1.95 events vs 0.99 event/100 patient-years; P <0.001), but multivariate analysis did not identify infliximab treatment to be an independent predictor of SSO development. Instead, CD severity and duration, ileal disease, and new corticosteroid use were found to be significantly associated with the occurrence of SSO. In the ACCENT I study, no increase in SSO was observed in patients who received infliximab compared with patients who were given other treatments. A second analysis of the TREAT registry led Lichtenstein and associates to prospectively evaluate the pre-specified safety-related outcomes of 6290 patients, 3179 of whom had received infliximab. The mean length of follow-up was 1.9 years. The mortality was similar for infliximab- and non–infliximab-treated patients (relative risk, 1.24; 95% confidence interval [CI], 0.73 to 2.10). Multivariate regression analysis identified only prednisone therapy to be associated with an increased risk for mortality (P = 0.016). Although an unadjusted analysis showed infliximab therapy to increase the risk of infection, a multivariate logistic regression analysis suggested that infliximab treatment was not an independent predictor of serious infection. Factors identified to be independent predictors of infection were prednisone use (P <0.001), narcotic analgesic use (P <0.001), and moderate-to-severe disease activity (P = 0.024). (Lichtenstein GR, et al. Am J Gastroenterol. 2006;101:1030–1038; Lichtenstein GR, et al. Clin Gastroenterol Hepatol. 2006;4:621–630.)

The hygiene hypothesis. The hygiene hypothesis for CD states that multiple childhood exposures to enteric pathogens decrease an individual's risk for developing CD later in life. Amre and others conducted a hospital-based case-control study (n = 194) to investigate the relationship between infection-related exposures and risk for CD in children. Their findings did not support the hygiene hypothesis, as physician-diagnosed infections in patients between the ages of 5 and 10 years were associated with an increased risk for CD. In addition, multivariate conditional logistic regression analysis revealed that a family history of inflammatory bowel disease (IBD), age, and owning a pet were also associated with the development of CD. In contrast, the results of a population-based case-control survey performed by Bernstein and co-workers revealed significant protective factors against CD, such as having pet cats before the age of 5 years and having larger families, that were consistent with the hygiene hypothesis. Factors associated with CD included being Jewish, having a first-degree relative with IBD, ever having smoked, and living longer with a smoker. An editorial by Lashner and Loftus suggests that differing results of these two case-control studies may be related to differences in study population, age at CD onset, genetic determinants, and different exposures to causative agents. (Amre DK, et al. Am J Gastroenterol. 2006;101:1005–1011; Bernstein CN, et al. Am J Gastroenterol. 2006;101:993–1002; Lashner BA, Loftus EV. Am J Gastroenterol. 2006;101:1003–1004.)

IBD

Long-term follow-up of tacrolimus therapy. Baumgart and co-workers retrospectively investigated the clinical data on 53 patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD (40 patients with ulcerative colitis [UC], 11 patients with CD, and 2 patients with pouchitis) who had been treated with tacrolimus. A total of 41 patients (77.1%) were also receiving azathioprine. The mean treatment duration was 25.2 months (range, 0.43 to 164 months) and the mean follow-up time was 39 months (range, 5 to 164 months). Among these patients, 31 (78%) who had UC, 10 (90.1%) who had CD, and both (100%) who had pouchitis achieved a clinical response or went into remission (as determined by the use of a modified clinical activity index) within 30 days of starting tacrolimus. Steroids were reduced or discontinued in 40 (90%) of 45 patients. The cumulative colectomy-free survival rate for patients with UC was estimated to be 56.5% at 43.8 months. Tacrolimus was well tolerated with few adverse events. These results demonstrated that tacrolimus is effective in refractory IBD and that long-term tacrolimus therapy is safe. (Baumgart DC, et al. Am J Gastroenterol. 2006;101:1048–1056.)

Acute gastroenteritis and risk of IBD. Garcia Rodriguez and associates examined the General Practice Research Database in Spain to investigate the relationship between infectious gastroenteritis and the occurrence of IBD. A cohort of 43,013 patients, aged 20 to 74 years, who had experienced an episode of acute infectious gastroenteritis, was identified. Results were compared with an age-, gender-, and calendar time–matched control group of 50,000 subjects without gastroenteritis. Both cohorts were followed for a mean of 3.5 years. The estimated incidence of IBD in the acute infectious gastroenteritis cohort was 68.4/100,000 person-years compared with 29.7/100,000 person-years in the control group (hazard ratio [HR], 2.4; 95% CI, 1.7 to 3.3). The relative risk of developing CD was greater than that of UC, especially during the first year after the infective episode (HR, 6.6; 95% CI, 1.9 to 22.4). These results indicate that infectious agents may play a role in the initiation or exacerbation of IBD. (Garcia Rodriguez LA, et al. Gastroenterology 2006;130:1588–1594.)

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