Implementing pharmacogenetics with CIPHER™

Personalized Medicine Program

Property of PGxl Laboratories

Kristen K. Reynolds, PhDVP Laboratory Operations11-20-14

Polypharmacy

Diabetes

Hyperlipidemia

Coronary Artery Disease

HypertensionThrombosisStroke

Depression

Psychosis

ADHD

Arrhythmia

ChronicPain

CIPHER manages the whole patient

Property of PGxl Laboratories

CIPHER interpretive support: Drug-Gene Pilot• Enhanced interpretive report format incorporating patient’s current med list

Drug-Drug InteractionsDRUG-DRUG INTERACTIONS:

ASPIRIN- PAROXETINE may result in an increased risk of bleeding.

ASPIRIN- CARVEDILOL or FUROSEMIDE may result in decreased diuretic and/or antihypertensive efficacy.

ASPIRIN- LOSARTAN may result in decreased antihypertensive effects and an increased risk of renal impairment.

CARVEDILOL- CLONIDINE result in increased risk of sinus bradycardia; exaggerated clonidine withdrawal response (acute hypertension).

LEVOTHYROXINE- PAROXETINE may result in increased levothyroxine requirements.

Property of PGxl Laboratories

Medications not metabolized or otherwise not accounted for in current genetic testing profile:ASPIRINCARBIDOPA/LEVODOPACLONIDINE CLOTRIMAZOLEFUROSEMIDELEVOTHYROXINELYRICASULFASALAZINE

Drug-Gene Pilot Stats (Feb-Sept 2014)General Cohort StatisticsPhysicians participating (GP, psychiatry, cardiology, pain management, gerontology)

27

Patients included (Feb-Sept 2014) 703

Total medications 8090Total drug-drug interactions found (excluding minor) 3113

Total meds with a genetic link 2955psychotropics 28%

cardiovascular 32%analgesics 20%

Other (allergy/asthma, cough, nausea, etc) 20%Avg number meds/patient 12Avg meds/patient with a genetic link 4

44% of medications with a potential gene link had a variant genotype identifying a Drug-Gene Conflict

Minor Moderate Major Contraindicated0

10

20

30

40

50

60

13%

52%

20%15%

% o

f med

icat

ions

wit

h co

nfli

ct

87%

PRODRUG OPIOIDS

43%

43% of opioids had CYP2D6 contraindication

SSRI ANTIDEPRESSANTS

single gene conflict

CYP and SLC6A4 conflict

40%

47%

87% of SSRIs had one or more gene conflicts

CARDIOVASCULAR MEDICATIONS

Statins

Losartan

Beta-blockers

Warfarin

Clopidogrel

0 10 20 30 40 50 60 70 80

Rosuvastatin 18% Simvastatin 23%

33%

49%

35%

63%

Atorvastatin 43%

% of medications with gene conflict

Drug-Gene Pilot feedback surveysQuestions(511 patients to date)

% of the cases

General comments

Overall % of patients for whom decisions changed based on report

52% • User friendly; easier to understand; like the colored symbols and alternative meds to consider

• Useful antidepressants, antipsychotics, anticoagulants, opioids

• “Drug-drug interactions were an eye-opening experience”

• “Overall reduction in total Rx meds was significant, 15-25%”

Used drug-drug interaction section 65%Switched a medication 57.5%Added or D/C medication without switch

50%

Avoided an entire class 52.5%Focused on an entire class 47.5%Adjusted dose of current medication 50%Made no regimen changes at all 45%Saw improvements in outcomes and/or patient satisfaction

67.5%

Summary• Many factors influence drug safety and efficacy

• CIPHER identifies significant risks across medication classes

• Genotyping a patient for a single indication, drug, or gene is unlikely to reveal the patient’s true risk burden based on their co-morbidities and polypharmacy

• Panel-based approach with drug-gene and drug-drug interactions improves sensitivity

– ID high-risk drugs, safer doses and/or better alternatives– different decisions 52% of the time resulting in improved outcomes and

satisfaction in 67% of cases

Do you have 1 or of these goals?

What is the cost of not havingPersonalized Medicine Program?

What are initiatives are you pursuing to reach these goals?

What would success look like for each of these goals?

What would achieving 1 or more of these goals mean?

Personalized Medicine Program Outcome Goals

Reduce Risk of ADRs

Reduce Cost of ADRs

Improve odds of reaching

therapeutic goals

Reach therapeutic goals

faster

Improve patient adherence to prescribers instructions

Improve patient satisfaction

Reduce regulatory

and/or legal risk

Innovative, Center of

Excellence

Decrease LOS

Decrease readmissions

Thank you!