Personalized medicine — tailoring
treatments to a patient's genetic make-up — made
a huge leap towards mainstream practice on August 16.
That's when the FDA announced the blood thinner warfarin
will now include genetic testing information on its
label. It should help docs figure out much faster the
right dose to prescribe, says the FDA.
Two genes drastically change the
way a patient responds to this drug. The first one,
VKORC1, makes the blood-clotting protein that's blocked
by warfarin, while the second, CYP2C9, makes the enzyme
that breaks down warfarin in the body. Any change in
their expression alters warfarin's concentration in
the blood.
And that could make the difference
between life and death. Warfarin is one of those drugs
with a 'narrow therapeutic index', so just a little
too much in the bloodstream can lead to strokes, while
a slightly lower concentration might cause a hemorrhage,
explains Dr Amalia M Issa, director of the Personalized
Medicine and Targeted Therapeutics Program at the University
of Houston.
Dr Issa (no relation to your reporter)
is very excited by the FDA's decision. "Personalized
medicine will likely transform the relationship between
the physicians and the pharmaceutical industry and the
way the pharmaceutical industry relates to the public,"
she told NRM by email.
TRIAL
AND ERROR
Until now, finding the right warfarin dose was a matter
of trial and error. Doctors check the blood's ability
to clot with different doses, using the prothrombin
time (PT) test, until they find the best one for their
patients. But the process could take weeks, leaving
the patients at risk of getting blood clots.
Enter the new one-stop dosing formula.
Researchers at the Washington University in St Louis
have come up with an algorithm that quickly estimates
a warfarin dose — while factoring in the genetic
differences. Their study appears in the September 1
issue of Blood.
Docs can use the formula online
(www.warfarindosing.org) and fill out their patient's
clinical info to get an initial estimate, while waiting
for the gene test results. Once those are in —
results are usually back in two to three days —
docs can plug in the results for a customized dose.
This should put an end to repeat visits, testing and
re-testing.
BUMPS
IN THE ROAD
But don't expect this trend to spread quickly to other
meds. "Currently, it is simply too expensive to do DNA
testing prior to prescribing drugs for all patients
and all conditions," says Dr Issa. Genotyping before
prescribing meds is already happening in some fields,
like cancer therapies, she notes. It's simply a matter
of deciding whether the genetic test would make a big
impact on the therapy — and is therefore worth
the expense — then doing it.
In the case of warfarin, the test
could save the healthcare system a bundle. The drug
sends more than 43,000 people to the emergency room
each year in the US and causes 85,000 serious bleeding
events and 17,000 strokes, according to an AEI-Brookings
Joint Center for Regulatory Studies study from November
2006 (which the FDA used to make its decision). Despite
its hefty price tag (up to $500 US) genetic testing
for warfarin could save the US $1.1 billion annually,
the thinktank estimates.
Familiarity with these tests is
another hurdle for the family physician to jump. "Increased
vigilance and knowledge is required to correctly interpret
lab results and explain them to patients," says Dr Issa.
That means learning more about pharmacogenomics —
which predicts a patient's response to drugs based on
their genetics — either through CME or other methods,
she adds.
An array of new genetic tests are
coming soon to a clinic near you. Clinicians will present
several new devices designed to fine-tune treatments
based on genetics — from an acoustic sensor for
cancer biomarkers to a sensitive blood test for early-stage
liver cancer — at the American Association for
Cancer Research conference starting September 17 in
Atlanta.
"Genomic technologies are being
improved all the time," says Dr Issa. She expects the
tools of the future will allow scientists to quickly
and inexpensively sequence entire human genomes —
pushing personalized medicine firmly into the family
practitioner's sphere.
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