IBD Watch^®

^{Timely Information for Practicing Physicians}

NOVEMBER 2005

Prevention of colorectal neoplasia. Evidence that mesalamine-based anti-inflammatory treatment may prevent colorectal cancer in patients with ulcerative colitis (UC) led Matula and associates to perform a proportional hazards analysis of 6-mercaptopurine (MP) and azathioprine (AZA) use. A total of 315 patients with UC who underwent surveillance colonoscopy were identified from a gastrointestinal pathology database and followed for an average of 8 years. No difference in rates of progression to neoplasia between MP/AZA users and non-users was identified. Thus, MP/AZA treatment of patients with UC was not observed to decrease or increase the rate of neoplastic transformation in the colon. (Matula S, et al. Clin Gastroenterol Hepatol. 2005;3:1015–1021.)

Effectiveness of colorectal cancer surveillance. Lindberg and colleagues reported the results of colonoscopic surveillance, conducted between 1977 and 2002, of all patients with UC from a defined area in Sweden. A total of 211 patients were studied; of these, 135 had total colitis and 69 had left-sided colitis. During surveillance, dysplastic changes were found in 52 patients and colorectal cancer was detected in eight; in one patient the cancer was fatal. Thirty-one patients underwent panproctocolectomy and another 18 patients had less extensive colonic resections. Colonoscopic surveillance appears effective in preventing death from colorectal cancer in patients with UC. (Lindberg L, et al. Scand J Gastroenterol. 2005;40:1076–1080.)

Small-bowel adenocarcinoma (SBA). Palascak-Juif and others studied 20 patients with Crohn’s disease (CD) and SBA and compared their data with those from 40 patients with de novo SBA. The cumulative risk of SBA was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. In patients with CD, SBA occurred within inflamed areas of the small bowel, and signet ring cells were found in 35% of cases. In contrast, de novo SBA was distributed all along the small intestine and signet ring cells were never found. The diagnosis of SBA was made preoperatively in only one of 20 patients with CD compared with 22 of 40 patients with de novo SBA. Survival was similar between the two groups. There are substantial differences between de novo SBA and the SBA associated with CD. (Palascak-Juif V, et al. Inflamm Bowel Dis. 2005;11:828–832.)

Effects of 5-aminosalicylates (5-ASAs) on renal function. de Jong and colleagues retrospectively surveyed 200 consecutive outpatients with CD to investigate the effects of long-term 5-ASA therapy on renal function. Among 153 evaluable patients with a mean exposure to 5-ASA of 8.6 years, creatinine clearance was found to decline by only 0.3 ± 5 mL/min per year. No cases of interstitial nephritis were reported. Multiple linear regression analysis identified duration of exposure to 5-ASA, but not cumulative dose of 5-ASA, to be predictive of change in creatinine clearance. Minimal decline in creatinine clearance, absence of interstitial nephritis, and lack of an association of creatinine clearance decline with the cumulative dose of 5-ASA indicate that renal failure is rarely caused by long-term 5-ASA treatment. (de Jong DJ, et al. Inflamm Bowel Dis. 2005;11:972–976.)

Infliximab-induced autoantibodies. Infliximab therapy of CD has been associated with the induction of antinuclear autoantibodies (ANA) and anti–double stranded DNA (dsDNA) autoantibodies. Nancey and others analyzed a large panel of serum autoantibodies drawn from 35 patients with CD who were treated with repeated infliximab infusions and 32 patients with CD who had never received infliximab. The induction of ANA and anti-dsDNA was observed in 53% and 35% of infliximab-treated CD patients, respectively. These patients did not develop autoimmune clinical symptoms. No other organ-specific or nonorgan-specific autoantibodies were detected. The humoral response induced by infliximab was restricted to the development of ANA and anti-dsDNA and was not associated with clinical signs of autoimmunity. (Nancey S, et al. Inflamm Bowel Dis. 2005;11:986–991.)

Impact of race and ethnicity. Basu and coworkers analyzed data from 148 patients with inflammatory bowel disease (IBD) who were followed between 1999 and 2003 to determine if differences exist among ethnic or racial groups. The study population comprised 40% white Americans, 37% African Americans, 20% Mexican Americans, and 3% Asian Americans. The predominant type of IBD in white and African Americans was CD, while Mexican Americans predominantly had UC. Compared with white Americans with CD, African Americans with CD had a higher incidence of arthritis and ophthalmologic manifestations, notably uveitis. Compared with Mexican Americans with UC, white Americans with UC had a higher incidence of joint symptoms and osteoporosis. A family history of IBD and colorectal carcinoma was found more frequently in white Americans than other ethnic groups and perinuclear antineutrophilic cytoplasmic antibody positivity was a more sensitive marker for UC in Mexican Americans than elsewhere. (Basu D, et al. Am J Gastroenterol. 2005;100:2254–2261.)

Pharmacokinetic effect of mesalazine on mercaptopurine metabolites. In vitro studies suggest that mesalazine interacts with mercaptopurine through an inhibition of thiopurine S-methyltransferase. Gilissen and colleagues studied the effects of mesalazine on the pharmacokinetic parameters of mercaptopurine in 17 patients with IBD. Following the discontinuation of mesalazine, thiopurine S-methyltransferase activity remained unchanged, but thioguanine levels decreased significantly and the methylmercaptopurine ribonucleotide/thioguanine ratio increased. These data demonstrate that mesalazine affects serum levels of mercaptopurine metabolites, but the mechanism is unclear. (Gilissen LPL, et al. Aliment Pharmacol Ther. 2005;22:605–611.) 

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