There's controversy brewing
in the world of Crohn's disease treatment. A pair of papers
in September's Gastroenterology disagreed concerning
the benefits of mesalamine ? a drug that ratchets down
the immune system ? in preventing the return of Crohn's
disease following intestinal resection. One study done
in Italy found no difference in recurrence rates when
another immunosuppressive drug, azathioprine, was compared
to mesalamine ? the therapeutic standard anti-inflammatory
drug in Crohn's. The Italians endorsed mesalamine because
fewer adverse effects were reported.
The second study, led by Dr Stephen
Hanauer of the University of Chicago Medical Center,
found 6-mercaptopurine (6-MP) to be superior to mesalamine.
But, justifiably or not, the latter article was trashed
in an accompanying editorial.
The multicentre Italian study was
led by Dr Sandro Ardizzone of the University Hospital
in Milan. Patients in this trial randomly got azathioprine
or mesalamine for 24 months. They were observed for
clinical relapse as defined by a Crohn's Disease Activity
Index (CDAI) score over 200 and complications requiring
surgical intervention.
The end result showed no difference
in risk of relapse between the groups, except in those
patients who had previously undergone an intestinal
resection ? in these cases azathioprine went gangbusters.
However, 22% of the folks taking azathioprine dropped
out due to adverse effects, compared to only 8% of those
taking mesalamine.
"Taking into account efficacy and
safety, mesalamine should... be considered as a first-choice
treatment in the prevention of postoperative relapse
of Crohn's disease," concluded the authors.
The five-centre American study
looked at 131 Crohn's patients who randomly received
6-MP, mesalamine or a placebo. After 24 months, the
proportion of patients who had suffered a clinical reoccurrence
as determined by life-table analysis was a sky-high
77% in the placebo crowd. Those taking mesalamine (58%)
and 6-MP (50%) faired much better.
When Crohn's relapse was endoscopically
determined, the rates were 64% for placebo, 63% for
mesalamine and a rock-bottom 43% for 6-MP. Dr Hanauer
and his colleagues concluded that "[6-MP] (but not mesalamine)
was more effective than placebo."
In an accompanying editorial, Drs
William Sandborn of the Mayo Clinic in Rochester, Minnesota,
and Brian Feagan of the University of Western Ontario
singled out Dr Hanauer's study for criticism. They pointed
to the discrepancy between the clinical relapse rate
(77%) found in the placebo group and the rate after
endoscopy (64%) and argued that it "likely reflects
the lack of a valid assessment of disease activity [and]
suggests that the clinical recurrence rates should be
interpreted with caution."
"The clinical recurrence rate was
based on the individual investigators' impressions of
the patient's status and was blinded to the endoscopic
findings," responded Dr Hanauer. "Some patients who
developed clinical recurrence [symptoms] did not undergo
endoscopy. We did not use a validated clinical score
such as CDAI as this has not previously been reproduced
or validated in postoperative studies."
The editorial's final statement
was that "the investigators' [conclusions are] not supported
by robust data." But Dr Hanauer defended his paper saying,
"The data is what it is."
"We believe based on this, as do
the majority of the readers, that there are benefits
from [6-MP] but I agree with the editorialists that
larger, dose ranging trials are needed," Dr Hanauer
conceded. "Unfortunately, these trials are extremely
expensive, difficult to enroll and will take another
five years, at best, to design and complete. We as physicians
need to combine our clinical trial data (as good or
bad as it is) with our clinical experience to treat
patients." As a final parting shot he added, "Unfortunately,
the editorialists would prefer to be therapeutic nihilists.
That's not what the majority of clinicians do or patients
prefer."
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