IBD Watch®
Timely Information for Practicing Physicians
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AUGUST 2005 Blockade of cellular adhesion molecules. MLN-02 is a humanized monoclonal antibody directed against the α4β7 integrin, a cellular adhesion molecule involved in the recruitment of leukocytes to the gut. In a multicenter, double-blind study, Feagan and colleagues randomized 181 patients with active ulcerative colitis (UC) to MLN-02 0.5 or 2 mg/kg intravenously, or placebo on days 1 and 29. Clinical remission at week 6 was achieved in 33%, 32%, and 14% of patients in the MLN-02 0.5- and 2-mg/kg groups, and the placebo group, respectively. Endoscopic remission was observed in 28%, 12%, and 8% of patients, respectively. An MLN-02 antibody titer >1:125 developed in 24% of patients and was associated with a lack of treatment benefit. These short-term results indicate that MLN-02 is an effective therapy for patients with active UC. (Feagan BG, et al. N Engl J Med. 2005;352:2499–2507.) Probiotic bacterial therapy. Bibiloni and colleagues administered VSL#3, a probiotic mixture of bacteria, twice daily for 6 weeks to 34 patients with active UC. The 6-week course of treatment was completed by 32 patients. Remission was achieved in 18 patients (53%), response was observed in 8 patients (24%), and no response or worsening of disease was noted in 6 patients (18%). Two bacterial components of VSL#3 were detected by polymerase chain reaction (PCR)/denaturing gradient gel electrophoresis in colon biopsies from 3 patients who were in remission. There were no reported adverse events related to VSL#3. These results suggest that VSL#3 may be effective therapy for patients with mild to moderate UC, and that probiotic bacteria were detectable in the therapeutic target site. (Bibiloni R, et al. Am J Gastroenterol 2005;100:1539–1546.) Leukocytapheresis treatments. Sawada and others performed a multicenter, double-blind study in which 25 patients with active UC were randomized to leukocytapheresis or a sham pheresis once weekly for 5 weeks followed by 1 session every 2 weeks for 4 weeks. Among 19 evaluable patients, clinical activity index scores improved in 80% of patients in the leukocytapheresis group compared with 33% of patients in the sham group. These results indicate that leukocytapheresis is a safe and effective treatment option for patients with active UC. (Sawada K, et al. Am J Gastroenterol. 2005;100:1362–1369.) Association of perianal disease with intestinal fistulization. Sachar and colleagues analyzed clinical information on 5,491 cases of Crohn’s disease (CD) from 6 databases in the US, France, Italy, and the Netherlands to determine the association between perianal CD and intestinal fistulization. Isolated ileal disease was present in 1,686 cases, and 1,655 patients had Crohn's colitis. An association between perianal disease and internal fistulization was not consistent across centers for patients with isolated ileal disease. However, for patients with Crohn's colitis, the association was strong and consistent with an estimated common relative risk of 3.4. Thus, there was a statistically significant association between perianal disease and intestinal fistulization in patients with Crohn's colitis but not patients with disease limited to the small bowel. (Sachar DB, et al. Am J Gastroenterol. 2005;100:1547–1549.) Prevalence of Mycobacterium avium subspecies paratuberculosis (MAP) in intestinal mucosal biopsies. Autschbach and others used IS900 PCR to detect MAP in intestinal biopsy samples from 100 patients with CD, 100 patients with UC, and 100 controls without inflammatory bowel disease. The IS900 PCR detection rate was higher in CD tissue samples (52%) than in UC (2%) or control (5%) specimens. IS900 DNA was detected in samples from regions in the small bowel and colon with CD involvement. No association between detection rates and CD phenotype was found. Corticosteroid treatment reduced the rate of IS900 detection. Sechi et al detected MAP by IS900 PCR on DNA extracts of fresh intestinal mucosal biopsies in 83% of 25 patients with CD in Sardinia, where MAP is endemic. MAP grew in cultures from 19 patients. An editorial by Shanahan and O'Mahoney reviews arguments for and against a causal link between MAP infection and CD. They concluded that standardized techniques are needed for the detection of MAP, and that achievement of sustained remission in patients with CD by anti-MAP therapy would provide the best evidence for an etiologic role for MAP in CD. (Autschbach F, et al. Gut. 2005;54:944–949, Sechi LA, et al. Am J Gastroenterol. 2005;100:1529–1536, and Shanahan F, O'Mahoney J. Am J Gastroenterol. 2005;100:1537–1538.) Infliximab: Maintenance for life vs episodic therapy. The merits of lifetime maintenance infliximab therapy were debated by Lichtenstein and Loftus. Lichtenstein stated that maintenance therapy provides superior outcomes to episodic treatments and is associated with less antibody formation. Loftus stated that financial costs and potential long-term safety risks need to be considered. Economic models of maintenance infliximab need further study, and updated reports from the TREAT registry may help address long-term safety concerns. Hanauer wrote that infliximab induction therapy alone does not alter the natural history of CD. The ACCENT I and II trials have demonstrated that 1 year of maintenance therapy benefits infliximab responders. If long-term therapy with infliximab becomes accepted, Hanauer believes that an important issue will be to define which patients should be started on infliximab. In addition, he indicates that episodic use or the use of infliximab as "bridge therapy" to an immune modifier may lead to the development of antibodies to infliximab and the loss of response to therapy. (Lichtenstein GR. Am J Gastroenterol 2005;100:1433–1439, Loftus EV. Am J Gastroenterol 2005;100:1435–1438, and Hanauer SB. Am J Gastroenterol 2005;100:1438–1439.) |
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