G e n o P A T H 2 0 9 L o n g w o o d D r i v e , S W H u n t s v i l l e , A L 3 5 8 0 1 8 5 5 - G E N O P A T H w w w . g e n o p a t h . c o m

 

   

Pharmacogenomics: The Case for Provider Practice Integration

2   Pharmacogenomics:  The  Case  for  Provider  Practice  Integration    

Introduction  Personalized medicine is becoming a reality in today’s healthcare environment. The successful milestone of mapping the human genome was achieved through the Human Genome Project in 2003 and marked the beginning of a new “normal” for how we think about diagnosing, understanding, and treating diseases in the human species. This area of science is expanding to cover a wide variety of challenges and opportunities. One specific subset of the broader context of personalized medicine is Pharmacogenomics. Pharmacogenomics is the study of how genes affect a person’s response to medications. This field combines pharmacology and genomics to both develop and administer effective, safe medications and doses that are tailored to a person’s genetic makeup. Clinicians can tap into a substantial knowledge base about how certain genetic variations are predictors for how a patient will respond to a wide variety of very commonly prescribed medications for immediately relevant clinical applications today. Available insights with respect to how patients uniquely respond to common prescriptions such as statins, blood thinners, blood pressure medications, pain medications, oral diabetic meds, anti-inflammatories and heartburn medications, to name a few, offer an alternative to “trial-and-error” prescription and the sometimes harmful side effects it can yield. The imperatives to take advantage of the insights of pharmacogenomics are well justified given the challenges to our healthcare system, not to mention the costs, suffering and/or fatalities attributed to ADE’s (Adverse Drug Events). It is estimated that ADE’s add an estimated costs of $3.5B/year in the US according to the US CDC.1 Estimates also suggest that if medication issues were classified as a disease, they would represent the 3rd or 4th largest cause of death in the United States. Certain patient populations are at a greater risk of suffering from these events and as such are the most likely to benefit from this type of personalized medicine. Providers face a myriad of challenges in today’s increasingly complex healthcare environment. It is important that this type of personalized medicine be introduced to practices in a way that is beneficial to the provider practice in order to be ultimately beneficial to patients. Successful integration requires understanding of the complicated workflow requirements of the practice and a partner who provides the practice with expertise, education, support and consultation. With the right approach and partnership, the integration of this type of personalized medicine into clinical practice can begin to deliver upon the promise of enhancing patient outcomes.

                                                                                                               1  http://www.cdc.gov/medicationsafety/basics.html

 

Pharmacogenomics:  The  Case  for  Provider  Practice  Integration   3    

Why  is  Pharmacogenomics  Important?  According to the FDA (Food and Drug Administration), “Pharmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dosages.” Adverse Drug Events (ADE’s) are a serious public health problem and it is anticipated that it will likely get worse as the population in the US ages. Pharmacogenomics utilized in personalized medicine can shift the emphasis in medicine from reaction to prevention, significantly reduce trial and error prescribing, help reduce the overall costs of healthcare, and improve the quality of care and outcomes for your patients. Furthermore, adverse drug reactions are a cost leader contributing to continued escalation of expense for malpractice. Adverse Drug Reactions are prominent in malpractice payouts by providers.      

   

4   Pharmacogenomics:  The  Case  for  Provider  Practice  Integration    

Pharmacogenomics  Basics  Genetic factors are estimated to account for between 20-95% of the patient variability with respect to responses to individual medications. Although humans share about 99% of the exact same exact genetic material, it is the 1% differences that make us unique. It is also some of these differences that determine how an individual will respond to a medication. When a drug is taken, there are two main processes that occur in the body:

1) Pharmacokinetics: How a drug moves through your body and gets metabolized or “absorbed” by the body’s systems. 2) Pharmacodynamics: How a drug changes the physiology of the body as it meets its “target” (e.g. the pain, or inflammation as examples.) In the case of how these processes occur, it is the Cytochrome P450 (CYP) system of genes that include the encoding enzymes that control the metabolism of more than 70% of prescription drugs.2 The variations that naturally occur through

genetic inheritance predict whether a patient will be either a poor, intermediate, normal, or rapid/ultra-rapid metabolizer of certain medications. Medications and associated recommended dosages are typically determined based on “average” success in clinical trials. With certain enzymes in the CYP450 family, however, the variations from normal metabolism are significant across our population. Greater than 75% of patients have significant variations falling outside of “normal metabolizers.” As an example, known population variances for these three enzymes exists as noted in the table below and can have significant implications for common prescription drugs such as Plavix, Coumadin, Warfarin, certain Beta Blockers, common pain medications and anti-depressants.

                                                                                                               2  Pharmacogenomics: Increasing the Safety and Effectiveness of drug therapy; American Medical Association  

Percentages of Population By Variation of Metabolism1

Poor  Metabolizer  

Intermediate  Metabolizer  

Normal  Metabolizer  

Rapid  or  Ultra  Rapid  Metabolizer  

Met

abol

ic V

aria

tions

Pharmacogenomics:  The  Case  for  Provider  Practice  Integration   5    

Genetic tests can uncover information with respect to these enzyme variations that suggest for specific drugs what type of metabolizer an individual will be. Genetic testing assays for particular genes and enzymes can disclose very critical information with respect to the efficacy of certain drugs for the patient and the dosing levels that will be appropriate. Just one example of available insights specific to one particular medication when a patient’s genetic tests highlight particular metabolizer variations is shown below:

Clopidogrel  (pro  drug)  Efficacy  

     

Poor  Metabolizer  

Population:  3-­‐5%  Whites;  13-­‐19%  Asians;  10-­‐20%  African  Americans  

Potential  Outcomes:  

-­‐  Not  Likely  to  receive  full  beneKit;  -­‐  Increased  Risk  of  stent  thrombosis  heart  attack  or  stroke.  

Intermediate  Metabolizer  

Population:  24-­‐36%  

Potential  Outcomes:  

-­‐  May  not  receive  full  beneKit;  -­‐  Increased  risk  of  stent  thrombosis  heart  attack  or  stroke;  -­‐  Recommended  to  consider  alternative  therapy.  

Normal  Metabolizer  

Population:  43-­‐73%  

Expected  to  beneKit  from  standard  dose;  

Rapid  /  Ultra  Rapid  

Metabolizer  Population:  

5%  

Potential  Outcomes:  

-­‐  Expected  to  process  medication  more  quickly;  -­‐  Possible  increased  beneKits;  Possible  increased  risk  for  bleeding/bruising.  

* Note: People with Asian and African ancestry tend to have an increased prevalence of poor metabolizer status.

Enzymes Normal Intermediate Poor Ultra Rapid CYP2D6 48% 35% 10% 7% CYP2C9 60% >35% 2-4% N/A CYP2C19 14-44% 24-36% 2-20% 30%

6   Pharmacogenomics:  The  Case  for  Provider  Practice  Integration    

Which  Patients  Tend  to  Benefit  the  Most  From  Pharmacogenomics?  A large and diverse group of patients may benefit from a combination of pharmacogenomics and comprehensive medication reconciliation. Commonly prescribed statins, chronic pain medications, chronic beta-blockers, SSRI, or anti-arrhythmic therapy meds are known to produce responses with significant variations based on the genetic characteristics of the patient. The growing population of aging adults in the US who are living longer, but often while managing multiple chronic conditions are prime beneficiaries of this type of medicine. Patients who are over 55 years of age and are taking two or more chronic medications frequently benefit from this type of personalized medicine. Additionally, the number of individuals who are taking five or more medications are very good candidates for this type of medication management. Primary care physicians are often the ones who are called upon to work with patients who are suffering from issues such as heartburn or pain management. Medications prescribed for these situations, not generally deemed as serious as chronic conditions, can in fact have unintended consequences for the patient because of other medications and/or their genetic predispositions with respect to metabolism. For these reasons, primary care provider practices often see tremendous benefits in integration of this type of personalized medicine into their practices. Certain medications, over 120 in total, actually have been deemed to be so potentially harmful due to known issues in patients with specific genetic alleles that they are required by the U.S. FDA (United States Food and Drug Administration) to carry “black box labels,” or pharmacogenomics biomarkers information in their labels.3 Some medications commonly

                                                                                                               3  www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm  

Pharmacogenomics:  The  Case  for  Provider  Practice  Integration   7    

prescribed by cardiologists fall into this category including medications such as Coumadin ® (Warfarin) and simvastatins. Finally, as the number of medications an individual takes increases, the situations in which a combination of pharmacogenomics and comprehensive medication reconciliation can provide excellent decision support also becomes more prevalent. Genetic traits provide predictable insights into how a patient will metabolize drugs and when drugs can become inhibitors or inducers in an individual providing valuable insight for identifying potentially harmful drug-to-drug interactions or situations in which the beneficial effects of one medication are diluted or altered by other medications.

CDC research conducted in 2010 showed that 66.2% of patients between the ages of 45-64 years have taken at least (1) prescription medicine in the last 30 days. The same study suggests that 16.8% of those individuals have taken (5) or more. The numbers for individuals who have taken (5) or more prescription drugs more than doubles for the 65 years or older demographic. Genetic pathways information combined with comprehensive medication reconciliation can provide a physician with significant decision support insights for these types of patients taking multiple medications.

8   Pharmacogenomics:  The  Case  for  Provider  Practice  Integration    

The benefits to the patients who fit in the profiles shown above can be significantly life altering at times. Expenses associated with ineffective treatments can be reduced. Adverse reactions and problematic side effects can be reduced. Ultimately, the efficacy of the treatment regime can be improved, yielding better outcomes for these patients.

   

Pharmacogenomics:  The  Case  for  Provider  Practice  Integration   9    

Provider  Practice  Considerations  The decision to integrate pharmacogenomics and personalized medicine into your practice can be a very positive one. The decision can have immediate and substantial benefits for your patients inclusive of:

• Saving your patients money on ineffective medications; • Preventing your patients from experiencing avoidable unpleasant or even fatal

experiences which can be attributed to certain medications; • Improving the efficacy of their comprehensive treatment plans, thus improving

their quality of life. Guidance from clinicians who have successfully implemented these programs often begin with these basic considerations for making the transition in your practice go smoothly:

1.    Integrate  pharmacogenomics  combined  with  increased  rigor  around  basic  comprehensive  medication  reconciliation  practices.  

2.    As  much  as  possible,  work  across  the  continuum  of  providers  for  your  patients  and  include  pharmacy  in  the  process.  

3.    Embrace  a  partner  in  the  process  who  is  qualified  and  willing  to  aide  in  educating  you,  your  staff,  and  your  patients  throughout  the  process.    For more information on how your practice can implement pharmacogenomics and produce better outcomes for your patients, contact GenoPATH at 1-855-GenoPATH (1-855-436-6728) or contact us at info@genopath.com.