Assessment of the clinical utility of pharmacogenomic testing on drug utilization in a high-risk patient population : an interim analysis using the upgrade registry

The potential benefits of incorporating pharmacogenomic (PGx) testing into clinical practice include minimizing adverse drug reactions (ADRs) and improving clinical outcomes based on genetic differences of individuals. Despite significant advances in bridging PGx from bench-to-bedside, there have been slower efforts to incorporate PGx testing into routine clinical practice due to the lack of robust evidence for clinical utility and convincing studies demonstrating improved health outcomes. The UPGRADE Registry, an interim, prospective, observational trial aimed at assessing several key aspects of PGx testing: 1) determining the total number of high-risk patients that had at least one drug change and its impact on patients; 2) describing the genetic polymorphisms representing populations in the US and Puerto Rico; 3) to evaluate the association between race/ethnicity and the percentage of drug changes; and 4) identifying individual factors (age, gender, co-morbidities, number of drugs, and race/ethnicity) affecting the number of drug changes implemented by practitioners. Approximately 25% of the entire cohort underwent drug changes after PGx testing results (defined as dose modifications, drug substitutions, and drug discontinuations); however, almost 50% of patients with adverse drug reactions (ADRs) with drug-drug or drug-gene interactions experienced subsequent therapeutic modifications. The ADR cohort reported herein also experienced significant decreases in the number of ADRs after PGx testing recommendations. The major subset of the UPGRADE population (95%) was characterized as experiencing a lack of drug activity (LOA); only 25% of these patients experienced any therapeutic drug modification. The UPGRADE registry confirms currently published literature that provides additional support to the distribution of polymorphic changes in drug metabolizing enzymes within the US population. There were no differences in the percentage of drug changes that occurred when comparing differing ethnicities, indicating a lack of healthcare disparity within this high-risk population. Several factors were identified as independent predictors of the number of drug changes. A positive relationship, (i.e. increasing the likelihood of drug change) was seen with number of drugs, gastrointestinal disorders, and hepatobiliary diseases. This prospective, observational, study demonstrated the potential of drug modifications in prevention of subsequent ADRs and improving LOA based on PGx testing of drug metabolizing enzymes. Additional education to clinical providers regarding the use and benefit of PGx testing is warranted based on guidance provided by our PGx testing results and a lack of subsequent drug changes.