Using genetic polymorphism as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients

S. Vegter, F.L. Muntinghe, M. Verduijn, E.W. Boeschoten, F.W. Dekker, G. Navis, M.J. Postma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: Pharmacological interventions that are of benefit in non-dialysis populations have thus far been disappointing in dialysis patients. Since clinical trials are expensive and time-consuming, adjunct strategies are needed to support decision making in prioritization of tracks for drug development. Genetic association studies may provide such a strategy when a genotype is associated with a well-defined molecular and functional phenotype. Previously an association with better survival was found in incident dialysis patients with systemic inflammation and a deletion variant of the CC-chemokine receptor 5 (CCR5δ32). Thus, we hypothesized that pharmacological CCR5 blockade could protect against inflammation associated mortality and estimated if such a treatment would be cost-effective. METHODS: Ascreen-and-treat strategy was modelled in which patients were screened for the CCR5δ32 polymorphism and patients with the wild-type genotype and high inflammation status were treated with CCR5 antagonists. a decision-analytic Markov model was used. Costs, utilities and clinical data on the association between CCR5 polymorphisms and mortality were all gathered from a single prospectively followed dialysis cohort (NECOSAD, n = 413). Univariate and probabilistic sensitivity analyses were performed. RESULTS: Pharmacological CCR5 blockade in patients with CCR5 wild-type and high inflammation status decreased mortality (RR = 0.61) and improved the probability of renal transplantation (RR = 2.41). The cost-effectiveness of the screenand- treat strategy was €18,557 per life-year gained and €21,896 per quality-adjusted life-year (QALY) gained. The main drivers of the cost-effectiveness were the costs of pharmacological CCR5 blockade and the reduction in relative risk of mortality. Threshold analyses were performed for these two parameters. CONCLUSIONS: Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potential cost-effective genetic screen-and-treat program. This study illustrates the potential of genetic association studies in drug-development programs, as a new source of Mendelian randomized evidence from an observational setting.
Original languageEnglish
Pages (from-to)477-478
Number of pages2
JournalValue in Health
Volume13
Issue number7
Publication statusPublished - 1-Nov-2010

Keywords

  • receptor
  • beta chemokine
  • chemokine receptor
  • hemodialysis patient
  • cost effectiveness analysis
  • genetic polymorphism
  • mortality
  • inflammation
  • human
  • patient
  • drug development
  • genetic association
  • genotype
  • wild type
  • dialysis
  • sensitivity analysis
  • quality adjusted life year
  • kidney transplantation
  • risk factor
  • population
  • clinical trial (topic)
  • decision making
  • phenotype
  • survival
  • model
  • clinical study

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