IBD Watch^®

^{Timely Information for Practicing Physicians}

APRIL 2007

ULCERATIVE COLITIS (UC)

Colectomy rates in a European cohort.  Hoie, et al conducted a prospective cohort study in which 781 patients with UC from 9 medical centers located in 7 countries throughout Europe and Israel were enrolled between 1991 and 1993.  The 10-year cumulative risk of colectomy was 10.4% in northern and 3.9% in southern European centers (p < 0.001; 8.7% incidence overall).  Colectomy was more likely in patients with extensive colitis compared to those with proctitis (hazard ratio of 4.1 (95% CI: 2.0-8.4).  Age at diagnosis, sex, and smoking status at diagnosis had no significant influence on colectomy rates.  These findings demonstrate colectomy rates lower than those found in previous reports.  The reason for geographic variation in colectomy rate is not known.  (Hoie O, et al. Gastroenterol 2007;132:507-515)  

Continuous infusion vs. bolus administration of steroids.  Bossa and others conducted a single-center, double-blind study in which 66 consecutive patients with a severe attack of UC were randomized to receive 1 mg/kg/day of 6-methyl-prednisonolone administered by either a bolus injection or continuous infusion.  A total of 40 patients (60%) had pancolitis and the remaining 26 patients (40%) had left-sided colitis.  Clinical remission was achieved in 16 of 32 patients treated with bolus injection and 17 of 34 patients treated with continuous infusion.  Twelve bolus-treated patients and 9 patients who received continuous infusion eventually underwent total colectomy.  Total colectomy was performed in the first month in 5 patients in each treatment group.  Steroid-related adverse events were experienced in 15 patients in the bolus administration group and in 13 patients in the continuous administration group.  Regression analysis identified previous use of steroids and active smoking to be independent predictors of nonresponse.  These findings demonstrated that the efficacy and safety results of a continuous infusion of methyl-prednisolone in patients with severe attacks of UC were similar to those achieved by bolus administration.  (Bossa F, et al. Am J Gastroenterol 2007;102:601-608)

 Meta-analysis of mortality.  Jess and colleagues conducted a meta-analysis of population-based inception cohort studies that investigated overall and cause-specific mortality in patients with UC.  The MEDLINE search engine and abstracts from international conferences were utilized to locate relevant studies.  A total of 10 studies fulfilled the inclusion criteria, reporting standardized mortality rates (SMRs) varying from 0.7 to 1.4.  The overall pooled SMR estimate was 1.1 (95% CI: 0.9-1.2; p = 0.42).  However, greater risk for death was observed during the first years of follow-up, in patients with extensive colitis, and in patients from Scandinavia .  Mortality due to gastrointestinal diseases, nonalcoholic liver disease, respiratory diseases, and pulmonary embolisms was increased.  In contrast, mortality from pulmonary cancer was reduced.  Overall, UC-related mortality accounted for 17% of deaths.  These data indicate that the overall risk of death for UC patients is similar to that of the general population.  However, subgroups of UC patients had a greater risk of mortality.  (Jess T, et al. Am J Gastroenterol 2007;102:609-617)

 INFLAMMATORY BOWEL DISEASE (IBD)

Allopurinol in azathioprine (AZA) or 6-mercaptopurine (6-MP) failures.  Sparrow et al used allopurinol to treat 20 IBD patients who had not responded to AZA/6-MP and had high 6-methylmercaptopurine metabolite levels in an effort to shunt metabolism of 6-MP to 6-thioguanine and improve clinical responses.  Allopurinol 100 mg daily was initiated and a dose of AZA/6-MP was decreased by 25% to 50%.  After allopurinol was started, mean 6-thioguanine levels increased from 191 to 400 pmol/8 x 108 red blood cells (p < 0.001).  As a result, the Harvey Bradshaw Index decreased in patients with Crohn’s disease (CD) from a mean of 4.9 to 1.5 points (p = 0.001) and the mean Mayo Scores in UC patients decreased from a mean of 4.1 to 2.9 points (p = 0.13).  The mean daily dose of prednisone was reduced from 17.6 to 1.8 mg (p < 0.001) and led to normalization of transaminase levels.  These data demonstrated that the addition of allopurinol to thiopurine nonresponders increased 6-thioguanine production leading to improved outcomes, reduced corticosteroid needs, and normalization of liver enzyme levels.  A potential risk of using allopurinol in combination with AZA/6-MP is the enhancement of myelosuppression and other toxicities associated with AZA/6-MP.  (Sparrow MP, et al. Clin Gastroenterol Hepatol 2007;5:209-214)

Role of smoking.  Three studies investigating the role of smoking in IBD have recently been published.  All 3 studies found that ex-smokers were older than current smokers and nonsmokers at the time of diagnosis of IBD.  Current smokers with UC had less colonic disease than ex-smokers or nonsmokers and one study showed that those with the least extensive disease were the heaviest smokers.  Current smokers with CD had less colonic disease than ex-smokers or nonsmokers.  The rate of development of strictures and the requirement for surgery was related to disease location, but was independent of smoking habit.  These studies indicate that smoking habit influences age at diagnosis and extent of disease.  The pathogenic basis for these observations is unknown and requires further investigation.  (Aldhous MC, et al. Am J Gastroenterol 2007;102: 577-588, Aldhous MC, et al. Am J Gastroenterol 2007;102: 589-597, and Tuvlin JA, et al. Inflamm Bowel Dis 2007;Epub ahead of print)

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