Senior Director, Epidemiology Alexion, AstraZeneca Rare Disease Boston, United States
Background: Hypophosphatasia (HPP) is a rare, hereditary metabolic disorder characterized by low tissue-nonspecific alkaline phosphatase (ALP) activity due to variants in the ALPL gene. While the diagnosed prevalence of perinatal/infantile onset HPP has been previously reported in the literature, the diagnosed prevalence of HPP overall is unknown.
Objectives: We sought to characterize the epidemiology of HPP, specifically the diagnosed prevalence and patient demographics, by performing a real-world analysis of a large electronic health record database in the US.
Methods: A population-based study was conducted using the ClarivateTM electronic health records database covering over 124 million lives, and includes records going as far back as 2011. Given a lack of ICD codes specific to HPP, this study relied on SNOMED CT codes, progress notes, and prescription(s) for asfotase alfa (Strensiq®), an enzyme replacement therapy that in the US is approved for the treatment of pediatric-onset HPP. Patients were required to have had two or more diagnoses for HPP (parent code for HPP 190859005 and associated child codes, or positive mention of HPP in the notes) ≥ 30 days apart, with at least one diagnosis on or before the prevalent year of interest; or at least one prescription for asfotase alfa on or before the prevalent year of interest. Patients were considered as prevalent in the calendar year of interest as long as the patient was observable in the data. Annual prevalence, inclusive of all HPP onset types, was calculated between 2018 and 2021, with adjustments in 2020 and 2021 for COVID-19 impacts on healthcare utilization.
Results: Between 2018 and 2021, an average of 577 prevalent HPP patients were identified in the electronic health records per year, yielding an average annual prevalence of 1.42 per 100,000 population. Females represented approximately 60% of the prevalent patients per year. Pediatric patients < 18 years accounted for approximately 19% of the prevalent patients per year, and adults ≥ 18 years approximately 81%, with the 35-to-49-year age group accounting for the largest portion of prevalent patients (~30% each year). Notably, the proportion of patients in the 65+ year age group increased from 18% in 2018 to 24% in 2021.
Conclusions: To the best of our knowledge, these findings provide the first population-based estimate of the diagnosed prevalence of HPP in the United States and points to the rarity of the disease. As diagnostic delay and misdiagnosis of HPP may occur, total prevalence of HPP may be higher than observed. Additional studies are needed to further quantify the prevalence of HPP and trends over time.
