Opportunity for Genotype-Guided Prescribing Among Adult Patients in 11 US Health Systems

Abstract

The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence of prescribed medications with an actionable pharmacogenetic association. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene-drug pairs as "level A," for which there is sufficiently strong evidence to recommend that genetic information be used to guide drug prescribing. The opportunity to use genetic information to tailor pharmacotherapy among adult patients was determined by elucidating the exposure to CPIC level A drugs among 11 Implementing Genomics In Practice Network (IGNITE)-affiliated health systems across the US. Inpatient and/or outpatient electronic-prescribing data were collected between January 1, 2011 and December 31, 2016 for patients ≥ 18 years of age who had at least one medical encounter that was eligible for drug prescribing in a calendar year. A median of ~ 7.2 million adult patients was available for assessment of drug prescribing per year. From 2011 to 2016, the annual estimated prevalence of exposure to at least one CPIC level A drug prescribed to unique patients ranged between 15,719 (95% confidence interval (CI): 15,658-15,781) in 2011 to 17,335 (CI: 17,283-17,386) in 2016 per 100,000 patients. The estimated annual exposure to at least 2 drugs was above 7,200 per 100,000 patients in most years of the study, reaching an apex of 7,660 (CI: 7,632-7,687) per 100,000 patients in 2014. An estimated 4,748 per 100,000 prescribing events were potentially eligible for a genotype-guided intervention. Results from this study show that a significant portion of adults treated at medical institutions across the United States is exposed to medications for which genetic information, if available, should be used to guide prescribing.

Figure 1.. Annual prevalence of exposure to at least one CPIC Level A drug by site (A) and to more or more CPIC Level A medications (B).

A) Exposure (log scale) to at least one CPIC Level A drug for each site from 2011–2016. Each colored circle represents the exposure for the corresponding site. Circles are absent for years where data are not available. The size of the circle is proportional to the number of patients eligible for drug prescribing during the calendar year. The dotted colored lines are the prevalence of exposure estimated from the model fit. The mean prevalence of exposure for the entire cohort weighted by site is represented by the solid black line and weighted by encounters is represented by the dotted black line. The 95% confidence bands for the two means are represented by gray shading but may be too narrow to be observed. B) Mean site-weighted prevalence stratified by at least one, two, three or four CPIC Level A drugs from 2011–2016 plotted on a linear scale. Note that confidence intervals are represented by gray shading but may be too narrow to be observed.

Figure 2.. Annual Prevalence of Exposure Stratified by CPIC Level A Drug or Drug Class.

Mean site-weighted prevalence of exposure (log scale) to a CPIC Level A drug or drug class from 2011–2016. Analgesic includes codeine, oxycodone, tramadol; Selective serotonin reuptake inhibitors (SSRIs) includes citalopram, escitalopram, fluvoxamine, paroxetine; Anesthetic includes desflurane, isoflurane, sevoflurane, succinylcholine; Tricyclic antidepressant includes amitriptyline, nortriptyline; Other includes allopurinol, ivacaftor, rasburicase; Immunosuppressant includes azathioprine, mercaptopurine, tacrolimus, thioguanine; Anti-seizure includes carbamazepine, phenytoin; Chemotherapeutic includes capecitabine, fluorouracil, irinotecan; HIV antivirals includes abacavir, atazanavir; Hepatitis C antivirals includes peginterferon alfa-2a/2b, ribavirin.

Figure 3.. Annual prevalence of exposure to A) statins, B) anticoagulants, and C) antiplatelets.

A) Top line represents all statins with exposure to individual statins shown in the lines below. Exposure to any statin increased over time, whereas exposure to simvastatin decreased and exposure to atorvastatin increased. B) Top line represents all oral anticoagulants with exposure to individual anticoagulants shown in the lines below. Exposure to warfarin decreased over time; however, warfarin remained the most commonly prescribed anticoagulant. C) Top line represents all oral antiplatelet P2Y12 inhibitors with exposure to individual agents illustrated with the lines below. Exposure to clopidogrel remained higher than for other agents. Note that confidence intervals are represented by gray shading but may be too narrow to be observed.

Figure 4.. Cardiovascular drug exposure compared between races.

Cardiovascular CPIC Level A drug exposure and alternatives compared between African American and white. Odds ratios were converted to risk ratios.