Effect Modification by Social Determinants of Pharmacogenetic Medication Interactions on 90-Day Hospital Readmissions within an Integrated U.S. Healthcare System

Abstract

The present study builds on our prior work that demonstrated an association between pharmacogenetic interactions and 90-day readmission. In a substantially larger, more diverse study population of 19,999 adults tracked from 2010 through 2020 who underwent testing with a 13-gene pharmacogenetic panel, we included additional covariates to evaluate aggregate contribution of social determinants and medical comorbidity with the presence of identified gene-x-drug interactions to moderate 90-day hospital readmission (primary outcome). Univariate logistic regression analyses demonstrated that strongest associations with 90 day hospital readmissions were the number of medications prescribed within 30 days of a first hospital admission that had Clinical Pharmacogenomics Implementation Consortium (CPIC) guidance (CPIC medications) (5+ CPIC medications, odds ratio (OR) = 7.66, 95% confidence interval 5.45–10.77) (p < 0.0001), major comorbidities (5+ comorbidities, OR 3.36, 2.61–4.32) (p < 0.0001), age (65 + years, OR = 2.35, 1.77–3.12) (p < 0.0001), unemployment (OR = 2.19, 1.88–2.64) (p < 0.0001), Black/African-American race (OR 2.12, 1.47–3.07) (p < 0.0001), median household income (OR = 1.63, 1.03–2.58) (p = 0.035), male gender (OR = 1.47, 1.21–1.80) (p = 0.0001), and one or more gene-x-drug interaction (defined as a prescribed CPIC medication for a patient with a corresponding actionable pharmacogenetic variant) (OR = 1.41, 1.18–1.70). Health insurance was not associated with risk of 90-day readmission. Race, income, employment status, and gene-x-drug interactions were robust in a multivariable logistic regression model. The odds of 90-day readmission for patients with one or more identified gene-x-drug interactions after adjustment for these covariates was attenuated by 10% (OR = 1.31, 1.08–1.59) (p = 0.006). Although the interaction between race and gene-x-drug interactions was not statistically significant, White patients were more likely to have a gene-x-drug interaction (35.2%) than Black/African-American patients (25.9%) who were not readmitted (p < 0.0001). These results highlight the major contribution of social determinants and medical complexity to risk for hospital readmission, and that these determinants may modify the effect of gene-x-drug interactions on rehospitalization risk.

Personalized medicine in a community health system: the NorthShore experience

“…After adjustment for comorbidities and other covariates, the odds of readmission were increased by more than 30% for patients with one or more CPIC PGx interactions (OR = 1.32, 95% CI 1.02-1.73) (p = 0.04) (David et al, 2021b). In a follow-up evaluation with roughly twice the sample size, led by Saulsberry and the PMED team, we replicated these findings and also showed that social determinants of health (including race, employment status, and income) were the major drivers of hospital readmission (Saulsberry et al, 2022). In fact, the odds of 90-day readmission for patients with one or more identified gene-drug interactions after adjustment for robust SDOH and other covariates was attenuated by 10% (OR = 1.31, 1.08-1.59) (p = 0.006).…”