P1600Cost-effectiveness analysis of genetic cascade screening in arrhythmogenic cardiomyopathy

Abstract

Background: Arrhythmogenic cardiomyopathy (AC) is an autosomal dominant inherited disease with incomplete penetrance and variable expression, and an important cause of sudden cardiac death in young adults. In the absence of genetic diagnosis, long-term follow-up of all first degree relatives is mandatory. Although the reported yield of the genetic test in AC probands is 50-60%, there is scarce data on the economic impact of the genetic cascade screening strategy. Objectives: To study the cost-effectiveness of the genetic cascade strategy in AC families. Methods: 151 patients from 41 families were consecutively enrolled in a Spanish referral Inherited Heart Disease centre. The cost of the genetic testing in each family was calculated adding the price of the proband study (NGS panel, €1380 in 2015) and cascade genetic screening (€200 each patient). The estimated price of the clinical work-up and follow-up of relatives without causal mutations who were discharge after genetic testing computed as cost-savings (diagnostic workup costs €819; follow-up visit costs €236/each). Incremental cost was the difference between the cost of genetic testing and the cost-savings generated by the genetic results. We also calculated the number of patients in each family who obtained benefit from the information provided by the genetic test. Results: We found 19 pathogenic mutations in 20 probands (detection rate = 49%), and 13 variants of unknown significance among the five main desmosomic genes (PKP2, DSP, DSG2, DSC2 and JUP). Among relatives, 12 had AC, 10 borderline diagnosis and 25 were carriers of mutation. 22 non-carriers could be discharge. The total incremental cost of the genetic cascade strategy was €12,514 (41 probands and 68 relatives genotyped) and 69 individuals benefit specifically from genetic results information. The incremental cost per causal mutation is €626 and the cost-per-patient benefit is €181 (Figure 1, red dot). Simulation studies showed that this strategy would be cost-saving if the price of the proband's genetic test was below €1074. The number of mayor diagnostic criteria in the proband (excluding genetics), and the number of children at risk (<14 years old) were independent predictors of the cost-effectiveness ratio in each family (p<0.011 for both). Conclusion: Genetic cascade strategy for familial screening in AC is costeffective with a willingness to pay of €181 per patient benefit. The relationship between the incremental cost and benefits in each family depends on the phenotype of the proband and the number of pediatric relatives. (Figure Presented).