Socio-demographic and genetic risk factors for drug adherence and persistence: a retrospective nationwide and biobank study across 5 medication classes and 1 845 665 individuals

Low drug adherence is a major obstacle to the benefits of pharmacotherapies and it is therefore important to identify factors associated with discontinuing or being poorly adherent to a prescribed treatment regimen. Using high-quality nationwide health registry data and genome-wide genotyping, we evaluate the impact of socio-demographic and genetic risk factors on adherence and persistence for 5 common medication classes that require long-term, regular therapy (N = 1 814 591 individuals from Finnish nationwide registries, 217 005 with genetic data from Finland and Estonia). Need for social assistance and immigration status showed a notable negative effect on persistence and adherence across the examined medications (odd ratios between 0.48 and 0.82 for persistence and between 1.1% to 4.3% decrease in adherence) while demographic and health factors showed comparably modest or inconsistent effects. A genome-wide scan did not identify genetic variants associated with the two phenotypes, while some pharmacogenes (i.e. CYP2C9 and SLCO1B1 ) were modestly associated with persistence, but not with adherence. We observed significant genetic correlations between medication adherence and participation in research studies. Overall, our findings suggest that socio-economically disadvantaged groups would benefit from targeted interventions to improve the dispensing and uptake of pharmacological treatments.