IBD Watch^®

^{Timely Information for Practicing Physicians}

SEPTEMBER 2007

Certolizumab pegol as treatment for Crohn’s disease (CD). Sandborn and others studied certolizumab pegol in 662 patients with moderate-to-severe CD who were randomized to receive 400 mg of the drug, or placebo, subcutaneously at weeks 0, 2, and 4, then every 4 weeks. Response rates at 6 weeks were 35% in the certolizumab group and 27% in the placebo group (P = 0.02), but remission rates did not differ significantly at week 6 or 26 (P = 0.17). The safety profiles between the two groups were similar. In a separate paper, Schreiber and colleagues reported the results of maintenance certolizumab therapy for patients who achieved a clinical response to certolizumab induction treatment in the Sandborn study. Patients who responded at 6 weeks were randomized to receive certolizumab, 400 mg, or placebo every 4 weeks through week 24. At week 26, response was maintained in 63% of certolizumab-treated patients compared with 34% of patients receiving placebo (P <0.001). Patients benefited from certolizumab regardless of whether they had previously received infliximab and whether they were taking glucocorticoids or immunosuppressants. Certolizumab pegol appears to be an active agent against moderate-to-severe CD. (Sandborn WJ, et al. N Engl J Med 2007;357:228–238; Schreiber S, et al. N Engl J Med 2007;357:239–250.)  

Confirmation of the role of ATG16L1. ATG16L1 was identified as a CD susceptibility gene in a German nonsynonymous single nucleotide polymorphism association study. Two independent case-control studies from Germany, a CD transmission disequilibrium test collection, and an independent cohort study from the United Kingdom confirmed these findings. A weak statistical interaction with CARD15 was observed, and no association with ulcerative colitis (UC) was demonstrated. The current study reported by Cummings and associates included 645 patients with CD and 676 patients with UC. Genotyping studies confirmed a strong association of ATG16L1 with CD. However, no statistical interaction was seen with the three known CD susceptibility genes, CARD15, 1L23R, or IBD5. (Cummings JR, et al. Inflamm Bowel Dis 2007;13:941–946.)  

Retrospective analysis of infliximab in patients with UC. Lees and others retrospectively analyzed a cohort of 39 patients with corticosteroid-refractory UC treated with infliximab. Twenty-six patients (66%) achieved a response to infliximab and avoided colectomy during the acute admission. Multivariate analysis identified hypoalbuminemia as a predictor of non-response. Two serious adverse events were reported: one death due to Pseudomonas aeruginosa pneumonia and one case of postoperative fungal septicemia. Infliximab is effective rescue therapy for some patients with acute severe UC; its associated toxicities should be discussed with patients prior to therapy. (Lees CW, et al. Aliment Pharmacol Ther 2007;26:411–419.)  

Immune responses to influenza vaccine. Mamula and co-workers conducted a prospective study in which a single-dose trivalent influenza vaccine was administered to 51 patients with IBD and 29 healthy controls. While the clinical activity of IBD was not affected by vaccination, patients with IBD who received infliximab or immunomodulatory therapy (corticosteroids, 6-mercaptopurine, methotrexate) were less likely to respond to two influenza vaccine antigens (P = 0.018 and 0.0002, respectively). These findings demonstrated that patients with IBD who receive infliximab or immunomodulatory therapy are at risk of inadequate response to vaccination. (Mamula P, et al. Clin Gastroenterol Hepatol 2007;5:851–856.)  

Epithelial barrier disruption and intestinal inflammatory response. The association of epithelial barrier disruption with intestinal inflammation in the interleukin (IL)-10 gene–deficient mouse may be due to an immune response to bacterial antigens. Sydora and colleagues used indomethacin to disrupt the intestinal epithelial barrier of IL-10 gene–deficient mice. Neither indomethacin alone nor oral gavage with nondisease-causing Bacteroides vulgatus alone caused an inflammatory response. However, intestinal exposure to both B vulgatus and indomethacin resulted in an inflammatory mucosal response. This experiment demonstrated that endogenous bacteria can cause an intestinal inflammatory response in the presence of epithelial barrier disruption in genetically predisposed animals. (Sydora BC, et al. Inflamm Bowel Dis 2007;13:947–954.)  

Reproduction in patients with IBD. Heetun and associates reviewed the literature for the best IBD management in reproductive and pregnant populations. While neither male nor female fertility is affected by IBD, sulfasalazine treatment reduces male fertility. Except for methotrexate, IBD drugs appear to be safe in pregnancy. Thus, treatment for the maintenance of remission during gestation is recommended and breast feeding is encouraged. Prospective trials are needed to guide clinicians. (Heetun ZS, et al. Aliment Pharmacol Ther 2007;25:513–533.)

Reviews. Rosh and others reviewed the association of lymphoma with IBD therapy in the August 2007 issue of Inflammatory Bowel Disease. A description of hepatosplenic T-cell lymphoma and case reviews of this complication of CD treatment are presented and available clinical options are explored. In late-breaking news from the 4th International Meeting on Inflammatory Bowel Disease (“On the Way to New Therapies”) held in Capri, Italy, April 9–12, 2006, Latella and others reviewed presentations dealing with genetics, bacteria-host interactions, immunomodulation, and tissue response, as well as the changing role of biotherapy, the risk-benefit ratio of novel therapies, and unmet medical needs. (Rosh JR, et al. Inflamm Bowel Dis 2007;13:1024–1030; Latella G, et al. Inflamm Bowel Dis 2007;13:1031–1050.)

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