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APRIL 2006
CROHN'S DISEASE (CD)
Randomized study of adalimumab therapy. Adalimumab is a human monoclonal
antibody directed against tumor necrosis factor (TNF). Hanauer and colleagues
report the results of a double-blind study in which patients with moderate to
severe CD who had not been exposed to prior anti-TNF therapy were randomized to
receive subcutaneous injections, at weeks 0 and 2, of adalimumab, 40 and 20 mg,
80 and 40 mg, or 160 and 80 mg, or placebo (the CLASSIC-I trial). Rates of
remission (defined as CD Activity Index scores of <150 points) at week 4 in the
adalimumab 40-/20-mg, 80-/40-mg, and 160-/80-mg groups were 18%, 24%, and 36%,
respectively, compared with 12% in the placebo group (P = 0.36, 0.06, and 0.001,
respectively). The adverse event profile was similar in all four groups. These
results show that adalimumab is an effective therapy in patients with moderate
to severe CD and that the optimal induction dose in this study was 160 mg at
week 0 followed by 80 mg at week 2. (Hanauer SB, et al. Gastroenterology.
2006;130:323–333.)
INFLAMMATORY BOWEL DISEASE (IBD)
Only non-specific inhibitors of both cyclooxygenase (COX)-1 and COX-2 induce IBD
flares. Previous reports have suggested that nonsteroidal anti-inflammatory
drugs (NSAIDs) may exacerbate IBD. Two articles in the February 2006 issue of
Clinical Gastroenterology and Hepatology address questions concerning the risks
of the use of NSAIDs in patients with IBD. In the first article, Sandborn and
others report the results of a double-blind study in which 222 patients with
ulcerative colitis (UC) in remission were randomized to receive celecoxib 200 mg
or placebo twice daily for 14 days. Disease exacerbation was observed in 3% of
celecoxib-treated patients and 14% of patients in the placebo group. Eleven
percent of patients in each group experienced a bowel-related adverse event. The
second article reports a study by Takeuchi and co-workers, who first treated
patients who had quiescent CD or UC with four NSAIDs for 4 weeks: acetaminophen
(n = 26), naproxen (n = 32), diclofenac (n = 29), and indomethacin (n = 22).
Next they treated four groups of patients who had IBD (20 patients per group)
with nonselective NSAIDs, a selective COX-2 inhibitor (nimesulide), and a
relatively selective COX-1 inhibitor (low-dose aspirin). Disease activity was
assessed using the Harvey-Bradshaw index, and clinical relapse was confirmed by
an increase in fecal calprotectin levels. The patients treated with nonselective
NSAIDs experienced a 17% to 28% relapse rate within 9 days of initiating
treatment while none of the patients receiving acetaminophen, aspirin, or the
selective COX-2 inhibitor demonstrated increased IBD activity. This suggests
that the mechanism inducing IBD flares requires concurrent inhibition of COX-1
and COX-2. According to an accompanying editorial by Korzenik and Podolsky,
these findings indicate that the use of nonselective inhibitors significantly
increases the risk for exacerbating IBD whereas short-term treatment with
celecoxib and, probably, low-dose aspirin may be safe for short-term use in
patients with IBD who are in remission. They also emphasized that while
celecoxib use is safe in certain patients with IBD, these data should not be
used to justify the widespread treatment of such patients with celecoxib. (Sandborn
WJ, et al. Clin Gastroenterol Hepatol. 2006;4:203–211; Takeuchi K, et al.
Clin Gastroenterol Hepatol. 2006;4:196–202; Korzenik J, Podolsky D.
Clin Gastroenterol Hepatol. 2006;4:157–159.)
Do life events trigger IBD relapse? Vidal and colleagues utilized a
version of the Social Readjustment Rating Scale to measure the impact of life
events in 163 patients with inactive IBD who had developed at least one relapse
within 2 years of study entry. Patients were followed to IBD relapse or for a
maximum of 11 months. IBD relapse occurred in 51 patients (32.9%). Multivariate
Cox regression analysis showed that the number of life events was not associated
with IBD relapse. In addition, the emotional impact of stressful events was not
associated with an increased risk of relapse. These results suggest that
stressful life events do not trigger exacerbations of IBD. (Vidal A, et al.
Am J Gastroenterol. 2006 [Epub ahead of print].)
Laboratory markers. Vermeire and associates reviewed the usefulness of
laboratory markers for diagnosis, disease activity assessment, and therapeutic
monitoring in patients with IBD. They concluded that laboratory markers can be
useful and should be part of the management of patients with IBD. However, until
more data are available, laboratory markers should be used as an additive tool
to clinical observation and physical examination. (Vermeire S, et al. Gut.
2006;55:426–431.)
Reviews
European consensus-based guidelines for the diagnosis and management of CD have
been published in a recent supplement of Gut (March 2006) and provide an
excellent evidence-based review of treatment. (Stange EF, et al. Gut.
2006;55[suppl 1]: i1–15; Travis SP, et al. Gut. 2006;55[suppl 1]:i16–35;
Caprilli R, et al. Gut. 2006;55[suppl 1]:i36–58.)
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IBD Watch®
