Estimated annual direct medical costs of manifestations among patients with activated phosphoinositide 3-kinase delta syndrome.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disease associated with heterogeneous manifestations, including recurrent infections, lymphoproliferation, and autoimmunity. This analysis sought to estimate the mean annual direct medical costs of manifestations associated with APDS. A burden-of-illness cost calculator was developed based on survey responses from the US clinical experts, published evidence, and the US cost sources (2023). Results from the survey provided estimates of mean annual prevalence of various manifestations associated with APDS and the mean number of times patients experienced recurrent manifestations in a year. In the base case analysis, the annual mean cost of manifestations associated with APDS per patient in the US was estimated to be $116,387 (range, $10,711-$417,455) with gastrointestinal-, infection-, and hematology-related manifestations being the largest contributing factors. The weighted average scenario analysis resulted in similar estimates of mean annual manifestation costs as the base case analysis. To our knowledge, our study is the first to provide estimates of annual prevalence of manifestations associated with APDS and to estimate the annual direct medical costs for patients with APDS in the US. The high mean annual cost associated with APDS contributes to the economic burden of patients and health care payers. Patients with APDS often require off-label, symptomatic treatments for various manifestations that do not target the root cause of the disorder. These treatments are associated with high costs that may not control symptoms. This analysis provides valuable support for discussions about resource utilization and the economic burden of APDS.