Children's Hospitals Today - Spring 2017 - 20

FEATURE / GENETICS

A

little boy who was otherwise healthy died after
surgery in Canada when he was just 2 years old.
The New England Journal of Medicine reported this
boy's case back in 2009: He received a codeine dose in the
recommended range, but an autopsy revealed that morphine
(a product of codeine metabolism) built up to toxic levels
in his blood and likely depressed his breathing. Genetic
profiling revealed he was an "ultra-rapid codeine metabolizer,"
meaning his liver converted codeine to morphine in higher
than normal amounts. This was due to a genetic variation in
an enzyme called CYP2D6-an enzyme that plays a role in
the metabolism of numerous drugs. This raises the question:
What if this patient's health care team knew about his genetic
variation before they prescribed the drug?
Enter pharmacogenomics. An emerging area of genetic
testing that some experts call the latest in personalized
medicine, pharmacogenomics is the study of how all genes
(the genome) influence drug response. "Much like a director
in a play or movie, genes give instructions to other parts
of the body," says Shannon Manzi, Pharm.D., director of
Clinical Pharmacogenomics Services at Boston Children's
Hospital. One of the things genes direct is the production
of enzymes that are required to break down or metabolize

Adverse drug events cause
26,500 deaths in children
each year in the U.S. alone.

Source: Canadian Pharmacogenomics Network for Drug Safety

the drugs a person takes. Enzymes influence how effective
a drug might be for someone and how likely he or she is to
experience side effects.
And that is one of the benefits pharmacogenomics brings
to pediatrics-reducing adverse drug events and improving
patient safety. The CDC says one in 250 Americans,
including children, seeks emergency care each year due to
an adverse drug event, and 27 percent of those visits require
hospitalization. Adverse drug events cause 26,500 deaths in
children each year in the U.S.
And experts say pharmacogenomics doesn't end
with reducing adverse events. "This testing can impact
outcomes-for length of stay, the cost of care and getting the
patient to an effective dose sooner," says Laura B. Ramsey,
Ph.D., assistant professor, Department of Pediatrics,
University of Cincinnati College of Medicine, and co-director
of Genetics Pharmacology Service at Cincinnati Children's
Hospital Medical Center.

20

CHILDREN'S HOSPITAL S TODAY Spring 2017

The work in action
Manzi and the team at Boston Children's are doubling
down on their work-the hospital has two separate arms of
Clinical Pharmacogenomics Services. On the research arm,
Manzi leads InforMEDKids, a study at Boston Children's in
partnership with the Medical College of Wisconsin (MCW)
and the Children's Hospital of Wisconsin Research Institute.
The study enrolled 650 patients from the hospital's epilepsy,
end-stage renal and inflammatory bowel disease programs
and the anticoagulation clinic within cardiology. The goal:
Use genetic information to understand children's reactions
to medications, ultimately helping clinicians select a more
individualized therapy for patients. In the end, this makes
medications safer and more effective.
Since 2012, Boston Children's has also offered targeted
pharmacogenomic clinical testing at the hospital and is
putting results into the electronic medical record. The hospital
started an outpatient service in 2014-one of only two in the
U.S. at the time. Today, the outpatient clinic sees children and
adults who have experienced adverse drug reactions or have
a history of non-response, says Manzi, who saw first-hand the
difference this testing can make for patients.
"We have a lot of stories of patients who did well once they
were placed on a drug that was more appropriate for them,"she
says. "Patients and families thank us for explaining what was
happening because multiple providers had trouble explaining
why they weren't responding to a medication-and in fact, it
was in their genes."

Standardizing testing
About 1,300 miles south of the team in Boston, a clinical trial
is taking place at St. Jude Children's Research Hospital in
Memphis. More than 3,700 St. Jude patients are enrolled in
the trial, called PG4KDS, with each being tested for hundreds
of gene variations that might be important for drug use. The
study selectively moves test results for a few genes into the
electronic medical record if the evidence strongly shows the
result can help in better prescribing of drugs for patients.
The main purpose of the trial: to make pharmacogenetic
test results easily available to St. Jude clinicians to inform
prescribing-all with the goal of making this a part of
standard care, according to Mary V. Relling, Pharm.D., chair
of the Pharmaceutical Sciences Department at St. Jude's,
and a member of the Steering Committee for the Clinical
Pharmacogenetics Implementation Consortium (CPIC). CPIC
is an international organization that creates guidelines
designed to help clinicians understand how available genetic
test results should be used to optimize drug therapy, rather
than whether tests should be ordered.
"At St. Jude's, we're looking at how frequently clinicians
use test results to alter prescribing," says Relling. "And how



Table of Contents for the Digital Edition of Children's Hospitals Today - Spring 2017

Contents
Children's Hospitals Today - Spring 2017 - Cover1
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Children's Hospitals Today - Spring 2017 - Contents
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