Prevalence and implications of cytochrome P450 substrates in Massachusetts hospital discharges

Abstract

The cytochrome P450 (CYP450) system of drug-metabolizing enzymes may contribute to individual variation in drug response. We examined prevalence of CYP450 substrates at hospital discharge for patients in two cohorts: insurance claims of Massachusetts residents and the medical records of two academic medical centers. The claims cohort included 47 473 individuals (38.2%) treated with at least one CYP450 2D6, 2C19, 3A4 or 1A2 substrate. The electronic medical records cohort included 45 905 individuals (57.4%) treated with at least one substrate. In adjusted models, substrates of CYP450 2D6 and 2C19 were associated with greater risk for 90-day readmission in both cohorts (odds ratios of 1.104 and 1.128 (P<0.001), respectively). Presence of any CYP450 substrate was associated with increased monthly medical costs (+$397, P<0.003). These analyses of more than 300 000 admissions using two different cohorts and data types indicate that CYP450 substrates are associated with greater readmission rates and greater health-care cost.

Pharmacogenetic testing among patients with mood and anxiety disorders is associated with decreased utilization and cost: A propensity-score matched study

“…Finally, we cannot distinguish test-specific effects from expectancy or placebo-like effects: tested individuals would be likely to anticipate benefit of test-guided treatment. Prior work suggested that pharmacogenetic testing with this assay increased adherence, but the present data did not allow us to examine the extent to which benefits may be mediated by improved adherence (McCoy et al, 2017). On the other hand, the reduction of 'hard' utilization outcomes, rather than, for example, clinician-assessed severity, suggests that placebo effects or improvement in adherence would need to be substantial.…”

“…Prior work suggested that pharmacogenetic testing with this assay increased adherence, but the present data did not allow us to examine the extent to which benefits may be mediated by improved adherence(McCoy et al, 2017). On the other hand, it is possible that clinicians order the test for less ill patients, while there is no evidence that this is the case based on cost prior to testing, if it were not addressed by propensity score matching this could falsely inflate the observed benefit.Second, the present study does not allow direct measurement of clinical efficacy and quality of life using standardized instruments or scales, another potential source of confounding.…”

“…A recent analysis of health care costs associated with CYP450 substrate prescription in the state of Massachusetts suggested a potential mechanism that may contribute at least in part to this benefit (McCoy et al, 2017). That study found that CYP450 substrate medications are associated with $397/month increase in health care costs and (in two cohorts) a 10-13% increase in odds of 90-day hospital readmission (McCoy et al, 2017).…”

“…A recent analysis of health care costs associated with CYP450 substrate prescription in the state of Massachusetts suggested a potential mechanism that may contribute at least in part to this benefit (McCoy et al, 2017). That study found that CYP450 substrate medications are associated with $397/month increase in health care costs and (in two cohorts) a 10-13% increase in odds of 90-day hospital readmission (McCoy et al, 2017). Similarly, a small study among antidepressant-treated patients undergoing pharmacogenomic testing specifically indicated greater utilization (in terms of number of visits) among individuals with possible gene-drug interactions (Winner, Allen, Altar, & Spahic-Mihajlovic, 2013).…”

Randomized, controlled, participant‐ and rater‐blind trial of pharmacogenomic test‐guided treatment versus treatment as usual for major depressive disorder

“…Cohort studies using claims data or electronic health records found that treatment with medications metabolized through the cytochrome P450 system was associated with greater medical cost and readmission, after accounting for differences in comorbidity, suggesting an opportunity to reduce cost by measuring this variation (McCoy, Castro, Cagan, Roberson, & Perlis, 2017). Naturalistic cost‐effectiveness studies likewise suggest that testing for common genetic variation may be associated with improved treatment outcomes.…”