IBD Watch®
Timely Information for Practicing Physicians
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OCTOBER 2006 CROHN’S DISEASE (CD) Novel serologic markers. Iris Dotan and colleagues utilized a glycan array and an enzyme-linked immunosorbent assay to test serum samples obtained from patients with CD or ulcerative colitis (UC) and normal healthy volunteers for the presence of anti-glycan antibodies. Antibodies against the glycans laminaribioside and chitobioside were found to discriminate between CD and UC (P<0.001 and P<0.05, respectively). The diagnosis of CD was suggested with a sensitivity of 77.4% and a specificity of 90.6% in patients with inflammatory bowel disease (IBD) who were positive for antibodies against laminaribioside, chitobioside, or mannan. Specificity was increased to 99.1% in those patients positive for at least two of these antiglycan antibodies. Higher titers of anti-bodies against laminaribioside or mannan were associated with small-intestine involvement (P=0.03 and P=0.0001, respectively). Furthermore, 12 (44%) of 27 anti-Saccharomyces cerevisiae antibody-negative CD patients were positive for anti-laminaribioside or anti-chitobioside antibodies. These novel antiglycan serologic markers may be useful for differentiating CD from UC and for disease stratification. (Dotan I, et al. Gastroenterol. 2006;131:366–378) Induction of tolerance to infliximab in patients with prior severe infusion reactions. C. Duburque and others conducted an induction-of-tolerance protocol in 14 CD patients who had experienced prior infusion reactions requiring suspension of infliximab treatment. Three infliximab infusions were planned, and each infusion of infliximab (5 mg/kg) was divided into 11 escalating increments of 15 minutes given over a 3-hour time period. Overall, 10 (71.4%) patients were able to tolerate all three infliximab infusions, and 7 (50%) patients achieved a complete remission. Two patients experienced severe immediate hypersensitivity reactions, and 3 patients had mild immediate hypersensitivity reactions that were controlled. One patient developed a delayed hypersensitivity reaction. These results demonstrate that some patients with CD who experience severe reactions to infliximab infusions may be safely re-treated with infliximab using an incremental induction-of-tolerance protocol. (Duburque C, et al. Aliment Pharmacol Ther. 2006;24:851–858) ULCERATIVE COLITIS (UC) Dose-finding study of oral tacrolimus. H. Ogata and coworkers randomized patients with refractory active UC to receive a high- trough concentration (10–15 ng/mL) of tacrolimus (HT group; n = 21), a low-trough concentration (5–10 ng/mL) of tacrolimus (LT group; n = 22), or placebo (n = 20). Oral tacrolimus was initiated at a dose of 0.05 mg/kg twice daily. At week 10, an improvement in disease activity index score (≥4 points, and all categories improved) was observed in 68.4% of patients in the HT group but in only 10% in the placebo group (P<0.001). Among patients in the HT group, 20% achieved a clinical remission and 78.9% had mucosal healing. The mean dose of prednisolone was reduced from 19.7 mg/day at baseline to 7.8 mg/day at week 10. The incidence of side effects was significantly greater in the HT group than in the placebo group. The most commonly reported adverse event was mild finger tremor. The results of this study show a dose-dependent response relationship of oral tacrolimus in patients with refractory UC. The optimal target range was a trough level of 10 to 15 ng/mL. (Ogata H, et al. Gut. 2006;55:1255–1262) INFLAMMATORY BOWEL DISEASE (IBD)
Survival and causes of
mortality. T.
Jess and coworkers followed a cohort of 692 patients with IBD from Olmsted
County, Minnesota, for a median of 14 years in order to analyze long-term
survival and causes of mortality. A total of 56 of 314 patients with CD died
(similar to 46 expected deaths), and 62 of 378 UC patients died (vs. 79.2
expected deaths). Among CD patients, 18 (32%) patients died from disease-related
complications, and 12 (19%) UC patients died from causes related to UC. Patients
with CD had an increased risk of dying from nonmalignant gastrointestinal causes
(standardized mortality ratio [SMR], 6.4; 95% CI: 3.2–11.5), malignant
gastrointestinal diseases (SMR, 4.7; 95% CI: 1.7–10.2), and chronic obstructive
pulmonary disease (SMR, 3.5; 95% CI: 1.3–7.5). In patients with UC,
cardiovascular death was reduced, and a diagnosis after 1980 was associated with
decreased mortality. Increased age at diagnosis and male sex were associated
with mortality in both CD and UC groups. Effective patient advocacy. J.C. Jaff and others provide a review of the advocacy needs of children and adolescents with IBD living in the United States. Although the article has a pediatric focus, adults have similar challenges and needs. (Jaff JC, et al. Inflamm Bowel Dis. 2006;12:814–823) New therapeutic target. The perisome [proliferators activated receptor gamma (PPARgamma) is a nuclear receptor that is highly expressed in the colon and plays a role in bacterial-induced inflammation. L. Dubuquoy and colleagues review the potential role of PPARgamma in the pathophysiology of IBD and the therapeutic strategy of targeting this receptor. (Dubuquoy L, et al. Gut. 2006; 55:1341–1349) |
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