Change in fracture rate and healthcare resource utilization among patients with hypophosphatasia following initiation of asfotase alfa: a retrospective US claims database analysis

Hypophosphatasia (HPP) is a rare, inherited, systemic disease characterized by skeletal and systemic manifestations. Asfotase alfa (AA) is the only US Food and Drug Administration-approved treatment for perinatal/infantile- and juvenile-onset HPP. Real-world data are scarce on fracture rates and healthcare resource utilization (HCRU) in patients treated with AA. This retrospective, observational study evaluated fracture-related outcomes and HCRU in patients with HPP treated with AA from January 2016 to December 2022 using the US Medicare Fee-for-Service and Inovalon Medical Outcomes Research for Effectiveness and Economics closed claims databases. Patients (≥2 yr of age) treated with AA (≥1 pharmacy claim for AA between January 2017 and December 2021 [identification period]) and ≥12 mo of continuous enrollment with medical and pharmacy coverage pre- and post-AA initiation were included. Clinical outcomes (change in fractures, types of fractures, and fracture event rates) and HCRU were assessed. Statistical analyses were performed to compare outcomes before and after initiation of AA. One hundred forty-nine patients (65.1% females, 69.1% adults; mean age, 39.6 yr) met the inclusion criteria. The proportion of patients experiencing fractures in the 12 mo following AA initiation significantly decreased compared to the 12 mo prior to treatment (18.1% vs 8.1%; <i>p</i> = .004). The mean fracture rate per patient per year nominally decreased post-AA initiation (0.24 vs 0.14; <i>p</i> = .096). The decrease was significant in fragility fracture rates (0.08 vs 0.02; <i>p</i> = .019). Most prescribed concomitant drugs at baseline were opioid analgesics (36.9%), nonopioid analgesics (34.2%), and antidepressants (34.9%). At baseline, 38.2% of patients were continuously using opioids and 21.8% were using high-dose opioids. Asfotase alfa initiation was associated with a statistically significant reduction in the proportion of patients experiencing fractures and fragility fracture rates, underscoring its potential therapeutic benefits.