IBD Watch^®

^{Timely Information for Practicing Physicians}

NOVEMBER 2004

CROHN'S DISEASE (CD)

Open-label study of adalimumab.  William Sandborn et al treated 24 CD patients who had lost responsiveness or developed intolerance to infliximab with adalimumab, a human monoclonal antibody directed against anti-tumor necrosis factor.  Adalimumab was administered subcutaneously in the following dosing schedule: 80 mg at week 0 and 40 mg every other week starting at week 2.  The adalimumab dosing schedule was allowed to be increased to 40 mg weekly after week 4 in patients who did not achieve clinical remission, complete fistula closure, and complete steroid withdrawal.  Among 17 patients with baseline CD activity index (CDAI) scores ≥ 220 points, 2 (12%) and 5 (29%) patients achieved clinical remissions (decrease of CDAI score to ≤ 150 points) at weeks 4 and 12, respectively.  Clinical response (decrease in CDAI score by ≥ 100 points) occurred in 7 (41%) and 10 (59%) patients at weeks 4 and 12, respectively.  The dosing of adalimumab was intensified to a weekly schedule in 19 (79%) patients.  No acute or delayed hypersensitivity reactions to adalimumab were reported.  These results showed that adalimumab was well tolerated and may be effective salvage therapy for patients with CD who have lost their response to infliximab or are unable to tolerate infliximab therapy.  (Sandborn WJ, et al. Am J Gastroenterol 2004;99:1984-1989)

Factors that influence progressive disease behavior.  Ben Smith and coworkers report the results of their retrospective analysis of clinical data from 231 CD patients with up to 20 years of follow-up after diagnosis.  Early age at diagnosis was associated with ileocolonic and upper gastrointestinal disease while positive anti-Saccharomyces cerevisiae antibody (ASCA) was associated with ileal involvement.  Smoking was protective against colonic involvement at diagnosis.  At 20 years of follow-up, 92% of patients had progressed to a more severe disease type.  Multivariate analysis identified ileal disease location and positive ASCA to be factors predictive for disease progression (p = 0.001 and 0.003, respectively).  In contrast, variant NOD2/CARD15 alleles were found to be associated with delayed disease progression.  (Smith BRK, et al. Inflamm Bowel Dis 2004;10:521-528)

ULCERATIVE COLITIS (UC)

Influence of diet on relapse.  J.L. Jowett and others from the University of Newcastle upon Tyne (Newcastle upon Tyne, UK) prospectively followed a cohort of 191 patients with UC in remission for one year to determine the effect of diet on relapse.  They found the consumption of meats (especially processed meats) protein, and alcohol (in the top tertile of intake) were associated with an increased likelihood of relapse (odds ratios of 3.2 [95%CI: 1.3-7.8], 3.00 [95%CI: 1.25-7.19], and 2.71 [95%CI: 1.1-6.67], respectively).  Further analyses also showed that high sulphur or sulphate intake from foods increased the risk for relapse.  The findings of this study indicate that modification of diet may influence the duration of remission in patients with UC and sulphur compounds in food may be responsible for mediating an increased likelihood of relapse.  Further studies are warranted. (Jowett JL, et al. Gut 2004;53:1479-1484)

INFLAMMATORY BOWEL DISEASE (IBD)

Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI).  Hypofibrinolysis may be an important cause of thrombotic events in patients with IBD.  In addition, increased plasma levels of TAFI, a recently described inhibitor of fibrinolysis, has been associated with an increased risk for venous thrombosis.  These findings led S. Saibeni and associates at the University of Milan (Milan, Italy) to evaluate TAFI plasma levels (ELISA) in 81 IBD patients, 81 sex- and age-matched healthy controls, and 30 patients with other inflammatory diseases (17 patients with Reiter's syndrome, 4 patients with Behcet's syndrome, and 13 patients with celiac disease).  Median TAFI plasma levels were higher in patients with IBD and other inflammatory diseases than in healthy controls (p ≤ 0.05 and ≤ 0.001, respectively).  High TAFI plasma levels occurred more frequently in patients with clinically active IBD compared to patients with clinically quiescent IBD (31.4% vs. 10.9%; p ≤ 0.03).  A correlation between TAFI plasma levels and erythrocyte sedimentation rate, C-reactive protein level, and alpha1-acid glycoprotein level was also observed.  These data showed that TAFI plasma levels were increased in IBD patients and correlated with acute-phase reactants.  No data concerning a relationship between TAFI levels and thromboembolic events in IBD patients were given and further study is warranted.  (Saibeni S, et al. Am J Gastroenterol 2004;99:1966-1970)

REVIEW

Guidelines for immunizations in patients with IBD.  Bruce Sands et al provide a review in the September 2004 issue of Inflammatory Bowel Diseases in which best-practice recommendations for immunization of patients with IBD are discussed.  Although there is evidence that the efficacy of immunization may be decreased in some patients undergoing immune suppression therapy, most immunizations are safely administered to patients with IBD even when they are immunologically compromised.  The authors conclude that for most IBD patients, recommendations for immunization do not deviate from recommended schedules for the general population.  (Sands BE, et al. Inflamm Bowel Dis 2004:10:677-692)

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