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MON-009 The Impact of Biomarker Screening and Cascade Genetic Testing on the Cost-Effectiveness of MODY Genetic Testing

Abstract Maturity onset diabetes of the young (MODY) is an autosomal dominant form of monogenic diabetes that is often misdiagnosed as type 1 diabetes (T1D) or type 2 diabetes (T2D). The most common MODY types are due to heterozygous mutations in the HNF1A, HNF4A, or GCK genes. Sulfonylureas are the first line treatment for HNF1A-/HNF4A-MODY, with stable or improved glycemic control compared to insulin (1). GCK-MODY, which manifests as stable hyperglycemia with no significant long-term complications, requires no treatment (2). Although early diagnosis leads to significant economic and quality of life benefits for patients with MODY, past cost-effectiveness studies have found that population-wide MODY genetic testing is not cost-effective due in part to low MODY prevalence (3). We sought to assess the combined effect of 1) biomarker screening to target genetic testing towards patients at high risk for MODY and 2) the addition of cascade genetic testing for first-degree relatives of affected probands on the cost-effectiveness of MODY genetic testing. We used simulation models of distinct forms of diabetes (HNF1A/HNF4, GCK, T1D, T2D) to forecast the clinical and economic consequences of this genetic testing strategy in pediatric patients over a 30-year horizon. In the testing arm, patients with HNF1A-/HNF4A-MODY switched to sulfonylureas, which was associated with a 1.0% reduction in HbA1c leading to lower rates of micro- and macrovascular complications. GCK-MODY patients switched to no treatment, without change in HbA1c. Patients with T1D or T2D experienced no change in care or outcomes in the testing arm. Study outcomes included costs, quality-adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER) (USD/QALY). Cost-effectiveness was defined as ICER less than $50,000 (typical threshold). Applying biomarker screening increased average quality of life (+0.0057 QALY) but also increased costs (+$280) in the testing arm relative to the control arm, yielding an ICER of $49,365. Adding cascade genetic testing increased quality of life (+0.0084 QALY) and lowered costs (-$268). Thus, applying biomarker screening to the MODY genetic testing strategy was cost-effective, and cascade genetic testing made the strategy cost-saving. National implementation of this strategy could improve the lives of patients with MODY while saving society money, which is a rare feat in personalized medicine. Reference: (1) Fajans and Brown, Diabetes Care, 1993;16(9):1254-1261. (2) Velho et al., Diabetologia, 1997;40(2):217-224. (3) Naylor et al., Diabetes Care, 2014;37(1):202-209. Sources of Research Support: Institutional Grant; The National Institute of Diabetes and Digestive and Kidney Diseases (P30, K24, K23, and R01)