SUN-529 Burden of Illness in Adults with Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry

Abstract

Background: Hypophosphatasia (HPP) is a rare, systemic, metabolic disease caused by tissue-nonspecific alkaline phosphatase deficiency, characterized by poor skeletal mineralization, muscle weakness and ambulatory difficulties. Limited data are available on the burden of illness in adults with HPP. Methods: Data from the Global HPP Patient Registry were used to identify adults (≥ 18 years old) who had a diagnosis of HPP (confirmed by low serum alkaline phosphatase activity for age and sex and/or an ALPL pathogenic variant) and who had never been treated with asfotase alfa (AA). The following components of disease burden were assessed in these patients: occurrence of clinical HPP manifestations, number of body systems affected by HPP manifestations, number of fractures/pseudofractures and use of pain medication. Patient-reported pain (assessed by the Brief Pain Inventory Short Form [BPI-SF]; scale 0 to 10; higher scores represent higher levels of pain), disability (assessed by the Health Assessment Questionnaire Disability Index [HAQ-DI]; scale 0 to 3; higher scores represent more severe disability) and quality of life (QoL; assessed by the 36-item Short-Form Health Survey version 2 [SF-36v2]; scale 0 to 100; higher scores indicate better QoL) were analyzed in relation to the number of HPP manifestations experienced. Results: Of the 218 adult patients (74% female) included in this analysis, mean (standard deviation [SD]) age at HPP diagnosis was 41.0 (18.8) years. Most patients had adult-onset (50%) or pediatric-onset (38%) HPP (33% and 5% of patients had juvenile- or infantile-onset HPP, respectively); age of onset was unknown for 12% of patients. The most common clinical HPP manifestations were chronic bone pain (60% of patients), generalized body pain (41%), and recurrent and poorly healing fractures (33%); 58% of patients had at least one fracture/pseudofracture (mean [SD] = 2.8 [2.6] per patient). Most patients (52%) had at least five clinical HPP manifestations, and 34% had manifestations in at least five body systems. Use of pain medication was reported in 41% of patients, 48% of whom were receiving opioids. Median self-reported pain scores on the BPI-SF were 3.6 (0-9.5) for pain severity and 3.1 (0-9.4) for pain interference in daily activities. Mean (SD) disability measured on the HAQ-DI was 0.5 (0.6). The mean (SD) physical component summary score of the SF-36v2 was 41.8 (10.8) and the mean (SD) mental component summary score was 45.6 (10.1); both scores were lower than the mean among the general population (50.0). There were significant correlations between greater numbers of HPP manifestations experienced and poorer scores on the BPI-SF, HAQ-DI and SF-36v2 (all p < 0.05). Conclusion: Adults with HPP who have never been treated with AA often experience pain and have a substantial burden of illness which can impact patient-reported QoL.