June
2007
Change in diagnosis from ulcerative colitis (UC) to Crohn’s
disease (CD). Melmed
and colleagues performed a nested, case-control study to identify predictors of
diagnostic change in 21 patients in whom a diagnosis of UC was changed to one of
CD. Clinical features in these patients were compared with those in 52 UC and 56
CD age-matched controls. Patients with a changed diagnosis were more likely to
have more extensive colonic involvement at initial colonoscopy than were UC
controls. Non-bloody diarrhea and weight loss of >10% at presentation were
independent predictors of diagnostic change. Serologic markers did not provide
additional information. Patients whose colitis appears with non-bloody diarrhea
and/or weight loss may be more likely to have CD than UC. (Melmed GY, et al. Clin
Gastroenterol Hepatol.
2007;5:602–608.)
Thiopurine
methyltransferase (TPMT) enzyme activity is predictive of azathioprine-induced
myelosuppression.
Winter and others sought
to determine if identifying TPMT status in patients with inflammatory bowel
disease (IBD) could predict side effects to azathioprine (AZA), and whether
screening for TPMT enzyme activity is superior to genotyping. In a group of 130
patients with IBD, AZA had been stopped in 25% because of toxicity. Of these
patients, four experienced severe myelosuppression, which may be associated with
reduced TPMT activity. Among 17 patients with reduced activity, 11 were
heterozygotes, including one patient who developed severe myelosuppression. The
heterozygote patients with intermediate TPMT activity did not experience side
effects. TPMT functional activity measurement was found superior to genotyping
in predicting severe myelosuppression. (Winter JW, et al. Aliment Pharmacol
Ther. 2007;25:1069–1077.)
Hepatosplenic T-cell lymphoma (HSTCL) following infliximab. An
association between the use of infliximab with purine analogues in young
patients with IBD and the development of HSTCL, a type of non-Hodgkin’s
lymphoma, has been recently reported. Rosh and co-workers review the issues of
lymphoma and IBD and available clinical options. (Rosh JR, et al. Inflamm
Bowel Dis. 2007 May 4 [Epub
ahead of print].)
Birth outcomes in Danish women related to therapy of women with CD. Norgard
and associates examined the impact of drug treatment on birth outcomes in women
with CD. They reviewed the Danish National Registry of Patients, the Birth
Registry, and the nationwide prescription database to identify a cohort of 900
children born to such women between 1996 and 2004. Logistic regression analyses
were used to estimate the relative risks of birth outcomes. Preterm births were
more prevalent among women exposed to steroids and/or AZA/6-mercaptopurine
(6-MP) compared with the reference group (12.3% and 25% vs 6.5%), while
congenital abnormalities were more prevalent among women exposed to AZA/6-MP
than in the reference group (15.4% vs 5.7%). The risk of congenital
abnormalities among AZA/6-MP–exposed women was 2.9 (95% confidence interval
[CI], 0.9 to 8.9). These data indicate that the relative risk of adverse birth
outcomes is increased in women with CD exposed to steroids and AZA/6-MP. The
study did not differentiate between therapies and disease activity as risk
factors for the adverse birth outcomes. (Norgard B, et al. Am J Gastroenterol. 2007 Apr 16 [Epub ahead of print].)
Adalimumab induction therapy. Sandborn
and colleagues conducted a double-blind, placebo-controlled study in which 325
patients with moderate to severe CD who could not tolerate infliximab or were
symptomatic despite infliximab therapy, were randomized to receive placebo or
adalimumab, 160 mg at week 0 and 80 mg at week 2. 4-week remission and
improvement (≥70-point CD Activity Index reduction) rates were greater
with adalimumab than with placebo (21% vs 7%; P
<0.001 and 52% vs 34%; P = 0.001,
respectively). No new safety signals were identified in this short-term study
that supported previously reported, uncontrolled data. (Sandborn WJ, et al. Ann
Intern Med. 2007 April 30 [Epub
ahead of print].)
Long-term colectomy rates after infliximab therapy. Jakobovits
and others conducted a retrospective cohort study of 30 patients with UC treated
with infliximab between 2000 and 2006. Sixteen patients (53%) underwent
colectomy at a median of 140 days after the first infliximab infusion (range, 4
to 607 days). No difference in colectomy rates was seen between patients
receiving infliximab for severe UC failing intravenous steroids (8 of 14) and
outpatients with steroid-refractory UC (8 of 16). Only 5 patients (17%) achieved
a steroid-free remission following infliximab therapy. The results indicate that
over half the patients with refractory UC underwent colectomy despite infliximab
treatment, and few patients sustained a steroid-free remission. (Jakobovitis SL,
et al. Aliment Pharmacol Ther.
2007;25:1055–1060.)
Weekend 5-aminosalicylic acid (ASA) enema maintenance therapy. Yokoyama
and associates conducted a study in which patients with UC in remission were
randomized to receive oral 5-ASA, 3 g/day for 7 days with or without 5-ASA
enemas (1g/day) on the weekend. The study was stopped at 24 patients because
relapse was reported in only 2 (18.2%) of 11 patients in the enema group
compared with 10 (76.9%) of 13 patients in the oral 5-ASA–alone group (hazard
ratio, 0.19 [95% CI, 0.04 to 0.94]. This demonstrated the benefit of adding
weekend 5-ASA enemas to oral 5-ASA maintenance therapy for patients with UC in
remission. (Yokoyama H. et al. Inflamm Bowel Dis.
2007 Apr 23 [Epub ahead of print].)
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