A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care
news • May 08, 2024
Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.
Introduction
Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization and mortality worldwide in both developed and developing countries [1–6]. ADRs account for 3–6% of hospital admissions in the United States, 2.5–10.6% of admissions in Europe, and 134 million adverse events occur annually in low- and middle-income countries (LMICs) due to unsafe care in hospitals, resulting in 2.6 million deaths [1–3, 7–11]. The costs of treating ADRs in a hospital setting vary between different units, with estimates of $13,994 in a nonintensive care unit (ICU) and $19,685 in an ICU setting [10–13]. Furthermore, ADRs are also associated with decreased patient compliance with treatment, leading to a substantial worsening of the disease, mortality and increased healthcare costs [12]. The potential to reduce morbidity and mortality through increased patient safety, fewer ADRs, and cost savings due to improved drug efficacy is immense [14, 15].
Although many ADRs are preventable and often attributed to human error, others appear to be idiosyncratic and potentially influenced by genetic factors [16–18]. Almost 50% of spontaneously reported ADRs may have identifiable causes, most likely explained by genetic variability [19, 20]. The genetic predisposition to ADR is increasingly known/investigated, particularly for anticancer, cardiovascular and neuropsychiatric therapeutics [19]. Several drug-specific severe idiosyncratic adverse effects, including severe hemolysis with glucose-6-phosphate dehydrogenase (G6PD) deficiency, malignant hyperthermia, epidermal tissue necrosis (Lyell’s syndrome and Stevens-Johnson syndrome), drug reactions with eosinophilia and systemic symptoms (DRESS), thyroid diseases, porphyria, aplastic anemia, long QT syndrome, and Brugada syndrome, are now explained by genetic predisposition [21–23].
Currently, the most common method for preventing ADRs due to prescribing drugs is the trial-and-error approach [24]. Four out of five patients are likely to carry a genetic variant that could alter the efficacy of commonly prescribed drugs [4]. Optimizing drug prescribing decisions based on patient genetic data may help reduce ADRs and improve drug effectiveness [24]. Pharmacogenomics (PGx) refers to the influence of various components of the genome on drug response, while pharmacogenetics (PGx) is a subcategory of pharmacogenomics that focuses on the role of genetic variation in drug targets, transporters and metabolizing enzymes and is known to predict some of the variability in drug effectiveness and safety [24]. PGx variants strongly affect drug disposition or metabolism, significantly contributing to the adverse outcomes associated with therapies [24]. At least one drug with a clinical annotation in the Pharmacogenomics Knowl edge Base (PharmGKB) was responsible for 30% of the ADRs upon hospital admission, suggesting that some of these ADRs could have been predicted through PGx testing [10, 11]. Preemptive PGx testing refers to the practice of testing an individual’s genetic makeup before prescribing any drugs that guide the selection of drugs and dosages that are most likely to be effective and well tolerated [24, 25]. The use of PGx can optimize drug therapy by identifying patients at risk of potential drug interactions and adverse events and guiding the selection of drugs and dosages that are most likely to be effective and well tolerated [24, 25]. Therefore, this narrative review aims to explore the current evidence on preemptive pharmacogenomic testing in healthcare for the prevention of ADRs and to discuss the gaps in the literature that need to be addressed to strengthen the implementation of such testing in healthcare settings.
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