OBJECTIVES:

To our knowledge, the economic burden of activated PI3K delta syndrome (APDS) is not well characterized. We designed a cost model to estimate the annual direct medical costs associated with APDS.

METHODS:

A conceptual model was developed, summarizing both APDS-associated manifestations and medications to treat APDS. Annual rates of manifestations and treatment use were estimated based on interim survey responses from experts currently treating patients diagnosed with APDS and assumed to be treated. Survey responses were weighted based on the number of patients with APDS treated by each respondent. To estimate costs for each manifestation and treatment, a targeted literature review was conducted. All costs were inflated to 2022 US dollars via the medical inflation index. The model used these values to estimate average annual direct medical costs based on the minimum and maximum manifestation and treatment rates reported in the surveys.

RESULTS:

The total estimated average annual cost among patients with APDS ranged from $83,057 to $793,620. The estimated annual cost of manifestations of APDS ranged from $12,242 to $322,939. Infections, hematologic pathology, and malignancy were the greatest drivers of costs due to annual APDS-associated manifestations. The estimated average annual treatment cost of APDS was $70,814 to $470,681. Immunoglobulin replacement therapy and hematopoietic stem cell transplantation were the greatest contributors to annual treatment cost, adding $37,963 to $94,907 and $23,143 to $289,293, respectively, to the average annual cost of care for patients with APDS.

CONCLUSIONS:

Activated PI3K delta syndrome is a rare disease with no approved treatments. Patients with APDS experience a range of manifestations requiring various treatment use that as a whole lead to high costs. The wide range of costs reflects the underlying heterogeneity of the disease. The occurrence of manifestations despite off-label treatments underscores the need for new, effective, and safe treatments for APDS.