JULY
2007
Natalizumab treatment for active Crohn’s disease (CD).
A
total of 509 patients with active CD associated with elevated C-reactive protein
(CRP) levels were randomized to receive natalizumab, 300 mg, or placebo
intravenously at weeks 0, 4, and 8; the primary end point was induction of
response (a ≥70-point decrease in the CD activity index [CDAI] score at
week 8, sustained through week 12). Response was achieved in 48% of natalizumab
patients compared with 32% of controls. Sustained remissions (CDAI score <150
points) were seen in 26% of natalizumab patients and 16% of controls. The safety
profile of the natalizumab group was similar to that of the placebo group.
Natalizumab is effective therapy for patients with active CD. (Targan SR, et al.
Gastroenterology 2007;132:1672–1683.)
Risk of vertebral fractures.
Vertebral
fractures occur in 14% to 22% of patients with CD and low bone mineral density (BMD).
Siffledeen and colleagues reviewed vertebral BMD analyses, radiographs, and
clinical data from 224 patients with CD to identify the prevalence of vertebral
fractures and risk factors in this population. The mean age of the cohort was
40.6 ± 11.0 years. A total of 45 patients (20%) had 88 vertebral fractures.
Sixteen of the 45 patients with fractures were found to have normal BMD. Linear
regression analysis identified elevations of body mass index, CRP, and
parathyroid hormone to be predictive of vertebral fractures. Low BMD and
corticosteroid use were not found to be significant risk factors. Vertebral
fractures may occur in patients with CD who have low and even normal BMD,
regardless of corticosteroid use. (Siffledeen JS, et al. Clin Gastroenterol
Hepatol 2007;5:721–728.)
Diagnosis and management of CD.
Epstein and associates
review current strategies for distinguishing CD from intestinal tuberculosis in
endemic areas. CD and intestinal tuberculosis have overlapping clinical,
radiologic, endoscopic, and histologic findings, but the treatment options
differ, and misdiagnosis has grave consequences. A diagnostic algorithm is
proposed and approaches to the management of CD, including the use of agents
that target tumor necrosis factor–alpha in patients at risk for tuberculosis,
are discussed. In a separate article, Hansen and colleagues review the reporting
of adverse events with infliximab, based on the Adverse Event Reporting System
database from 1968 to 2005. They found adverse event signals for the development
of infliximab-induced lymphoma, neuropathy, infection, and bowel obstruction.
The signal for granulomatous infection was stronger than that for non-granulomatous
infection. The signal for bowel obstruction was specific to patients with
inflammatory bowel disease (IBD), suggesting potential confounding by
indication. Clinicians need to stress the increased risk for lymphoma,
neuropathy, and granulomatous infections with the use of infliximab. (Epstein D, et al. Aliment
Pharmacol Ther
2007;25:1373–1388; Hansen A, et al. Clin Gastroenterol Hepatol
2007;5:729–735.)
Mesalamine formulation determines effectiveness. Steinhart
and others reviewed 13 randomized controlled trials published in the literature
that showed that treatment with pH 7–dependent mesalazine significantly
reduced the risk of relapse in patients with CD in remission. In contrast, pH
6–dependent mesalazine and controlled-release mesalazine did not show an
advantage over placebo. Further studies of pH 7–dependent mesalazine
formulations are warranted in the maintenance of CD remissions. (Steinhart AH,
et al. Aliment Pharmacol Ther 2007;25:1389–1399.)
Endoscopic mucosal resection (EMR) of flat neoplasia. Limited
data exist to support EMR of exophytic adenoma-like mass (ALM) lesions in
patients with ulcerative colitis (UC). In the current study, the safety and
clinical outcomes of patients with UC undergoing EMR for Paris class 0–II and
class I ALM were prospectively investigated. A median of six colonoscopies per
patient was performed in 169 patients with UC (median follow-up, 4.1 years).
Among these patients, 204 lesions (170 ALMs, 18 dysplasia-associated lesion
masses, 16 cancers) were diagnosed and managed safely by EMR. While the median
lesion diameter and interval cancer rate did not differ between the UC study
cohort and historical controls without UC treated with EMR, the UC group had a
greater prevalence of Paris class 0–II lesions (61% vs 35%) and a higher rate
of recurrence of lateral spreading tumors (14% vs 0%). The authors propose that
the resection of flat dysplastic lesions include EMR in selected cases. (Hurlstone
HR, et al. Gut 2007;56:838–846.)
IBD and pregnancy. Cornish and colleagues conducted a Medline literature search
to determine pregnancy outcomes in women with IBD. A total of 3,907 patients
with IBD and 320,531 controls were reported in 12 studies. The incidence of low
birth weight in newborns of women with IBD was twice that of newborns of
controls. There was also a 1.87-fold increase in the incidence of prematurity in
pregnancies of women with IBD, who were also 1.5 times more likely to undergo
caesarian section. Furthermore, the risk of congenital abnormalities was
2.37-fold greater in babies born to women with IBD compared with controls. These
results indicate that pregnant women with IBD should be treated as a group at
high risk for adverse outcomes. (Cornish J, et al. Gut
2007;56:830–837.) Editors’ note: This report fails to take into account disease
activity and medications which, in the editors’ experience, keep pregnant
women well throughout pregnancy and after delivery.—S.H.
IBD Watch®
