Key Pharmacogenomic Considerations for Sickle Cell Disease Patients

Abstract

Sickle cell disease (SCD), although a monogenic disease, exhibits a complex clinical phenotype that hampers optimum patient stratification and disease management, especially on hydroxyurea treatment. Moreover, theranostics, the combination of diagnostics to individualize and optimize therapeutic interventions, has not been firmly on the forefront of SCD research and clinical management to date. We suggest that if tailor-made theranostics in SCD is envisaged, pharmacogenomics is anticipated to be the way forward. Herein, we present the current key pharmacogenomic opportunities and challenges in SCD, considering population variation, ethics, and socioeconomic aspects. We focus on pharmacogenomics and pain management, genethics, and cost-effectiveness in SCD. We searched for and synthesized data from PubMed and Google Scholar, and the references from relevant articles, using the keywords "pharmacogenomics," "sickle cell disease," "hydroxyurea," "ethics," "pain management," "morphine metabolism," "opioids," "pharmacogenomics and chronic pain," "cost-effectiveness," and "economic evaluation." Only articles published in English were included. So far, when pharmacogenomics in SCD has been considered, interindividual variability in hydroxyurea response/toxicity has been of primary interest. We underscore the need to extend pharmacogenomic considerations on other therapeutic interventions currently present using a holistic patient-centric approach, and taking disease complications into account as well. Furthermore, we raise awareness toward socioeconomic, ethical, and population differences in the way sickle cell pharmacogenomics might unfold in the future. If pharmacogenomics in SCD is to be used in the clinic in an evidence-based manner, cost-effectiveness and population-specific empirical ethics data are urgently needed.

Keywords: economic evaluation; ethics; pain management; pharmacogenomics; sickle cell disease.