IBD Watch^®

^{Timely Information for Practicing Physicians}

DECEMBER 2005

CROHN'S DISEASE (CD)

Natalizumab therapy. Sandborn and colleagues conducted two controlled trials to evaluate natalizumab, a humanized monoclonal antibody directed against alpha-4 integrin, as induction and maintenance therapy in patients with active CD. In the first trial, 905 patients were randomized to receive natalizumab 300 mg or placebo at weeks 0, 4, and 8. In the second trial, 339 patients who had achieved a response to natalizumab were randomized to continue the drug or receive placebo every 4 weeks through week 56. Small differences in response (56% vs 49%; P = 0.05) and remission rates (37% vs 30%; P = 0.12) were observed between the natalizumab and placebo groups during induction therapy. However, maintenance therapy with natalizumab resulted in higher rates of sustained response (61% vs 28%; P <0.001) and remission (44% vs 26%; P = 0.003) through week 36 than did placebo. The safety profile was similar between the two treatment groups. Of note, in an open-label extension study, one natalizumab-treated patient died of progressive multifocal leukoencephalopathy associated with a human polyomavirus (JC virus). These results demonstrated that maintenance therapy with natalizumab in patients with active CD significantly increased the rates of sustained response and remission. This clinical benefit must be weighed against the risk of serious adverse events such as progressive multifocal leukoencephalopathy. (Sandborn WJ, et al. N Engl J Med. 2005;353:1912–1925.)

ULCERATIVE COLITIS (UC)

5-aminosalicylate (ASA) use and colorectal cancer risk. To evaluate the risk of colorectal cancer in patients taking 5-ASA for inflammatory bowel disease (IBD), van Staa and colleagues reviewed the General Practice Research Database in the United Kingdom to identify patients who had IBD and used 5-ASA. Among 18,969 patients identified, 100 had developed colorectal cancer during 5-ASA exposure. Most of these cases of colorectal cancer (76%) occurred in patients with UC. A case-control analysis revealed that regular users (patients having received at least six prescriptions for 5-ASA in the previous 12 months) had a decreased risk of colorectal cancer compared with irregular users (adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.38 to 0.96). Thus, these data add support to recent findings suggesting that regular 5-ASA use by patients with UC is associated with some reduction in the risk of colorectal cancer. (van Staa TP, et al. Gut. 2005; 54:1573–1578.)

Impact of ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC) who have UC. Right-sided colorectal cancer may develop in patients with PSC who also have UC due to high concentrations of bile acids. In the current study, Wolf and associates report the results of a retrospective analysis of patients with PSC and UC, 28 of whom were treated with UDCA and 92 of whom were not. The cumulative incidence of dysplasia or cancer did not differ between the two cohorts of patients. However, the cumulative mortality of UDCA-treated patients was significantly lower than that of patients who had not received UDCA therapy. These data suggest that UDCA treatment may reduce the mortality due to colorectal cancer in patients with PSC and UC. (Wolf JM, et al. Aliment Pharmacol Ther. 2005;22:783–788.)

INFLAMMATORY BOWEL DISEASE (IBD)

Thiopurine-induced liver injury. Bastida and others prospectively followed 161 patients with IBD who were receiving thiopurine to assess the incidence, risk factors, and clinical course of thiopurine-induced liver toxicity. Abnormal liver function was detected in 21 patients (13%) and hepatotoxicity occurred in 16 patients (10%) after a median of 85 days of therapy. Treatment was withdrawn in five cases. Corticosteroid use was associated with hepatotoxicity (OR, 4.94; 95% CI, 1.01 to 23.96), and plasma gamma-glutamyl transferase levels at the onset of hepatotoxicity were predictive of treatment withdrawal (area under the receiver operating characteristic curve, 0.95). Concomitant therapy with anti–tumor necrosis factor therapy was found to be protective against liver injury (OR, 0.3; 95% CI, 0.1 to 3.1). Editor’s Note: Biopsy data were not included and will be valuable to assess the ultimate risk of thiopurine compared with azathioprine/6-mercaptopurine. (Bastida G, et al. Aliment Pharmacol Ther. 2005;22:775–782.)

Oral medication adherence in a pediatric population. Mackner and Crandall conducted a study of oral medication adherence that included 50 children aged 11 to 17 years who had IBD, and their parents. Parents completed an adherence interview and Child Behavior Checklist, Family Assessment Device, and demographic questionnaires. Children completed the adherence interview and the Piers Harris Self-Concept Scale, Children's Depression Inventory, and Coping Strategies Inventory questionnaires. Treating gastroenterologists completed the Pediatric Crohn's Disease Activity Index. The adherence interview results showed parent-child concordance to be high. Family dysfunction and poor child coping strategies were associated with poorer adherence. A correlation between poorer adherence and behavioral/emotional problems approached significance. These data suggest that oral medication adherence should be monitored, especially in children with poor coping strategies, and that psychotherapy be initiated when appropriate to improve adherence. (Mackner LM, Crandall WV. Inflamm Bowel Dis. 2005;11:1006–1012.)

Review: A discussion of the design and outcomes of IBD clinical trials is included in the November supplement of Inflammatory Bowel Disease. (Sands BE, et al. Inflamm Bowel Dis. 2005;11[suppl 1]:S22–S28.)

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