Docs have been treating Crohn's
disease the wrong way around, according to a study in
the February 22 issue of The Lancet. Forget the
"step-up" approach, suggest the Canadian and European
researchers; lay on the infliximab from the outset and
get your patients in remission faster.
"The conventional approach uses
corticosteroids as initial therapy, then if that fails,
move up the ladder to immunosuppressants, then finally
add the drug infliximab," says study author Dr Brian
Feagan, an epidemiologist at the University of Western
Ontario in London, ON.
Infliximab, a tumour-necrosis factor
(TNF) antagonist, strikes at the inflammatory response
which triggers the disease. Although it's proven effective,
the drug currently sits on the bottom rung in the treatment
of the gastrointestinal chronic inflammatory disorder.
Steroids, which control Crohn's disease symptoms like
abdominal pain and bloody diarrhea, are favoured.
"But that therapy approach is not
evidence-based," reveals Dr Feagan. So he and fellow
researchers took a cue from a recent study on rheumatoid
arthritis, another chronic inflammatory disease, that
showed that the opposite, top-down approach was safer
and more effective.
BOTTOMS
UP
The Lancet study randomized 133 patients to receive
either combined immune-suppressing drug with intermittent
infliximab or conventional treatment — meaning
corticosteroids, followed by immunosuppressants and
finally infliximab. All patients had been only recently
diagnosed with Crohn's and hadn't been on steroids or
any of the other drugs used.
Within six months, 60% of the combined
therapy group were in remission, compared to only 36%
of the conventional treatment group. What's even better
is that the combo group never needed corticosteroids,
which are associated with a greater risk of mortality,
or surgery, as is sometimes necessary with advanced
disease.
CHANGING
PARADIGMS
Despite the promising results, there are hurdles to
overcome before the top-down approach makes it to clinical
practice — chief among them is infliximab's cost.
The drug is much more expensive than steroids and though
it's approved in Canada for treatment of Crohn's, most
provinces won't cover it unless all other options have
been exhausted.
But drug acquisition cost is not
an accurate way to judge a therapy, argues Dr Feagan.
"You have to look at the cost of not being in remission.
These patients end up on several drugs or worse, in
the hospital," he says.
Another concern is the fact that
the study's data "are not sufficient to assess the frequency
of serious infections, cancers and other adverse events,"
writes Mayo Clinic gastroenterologist William J Sandborn,
in an accompanying editorial. He points to a larger,
ongoing trial which is looking at the safety of this
approach. If those results — coming out later this
year — confirm Dr Feagan's and his colleagues',
then "the treatment algorithm for patients with Crohn's
disease will change," he adds.
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