Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry

Abstract

Background: Hypophosphatasia (HPP) is a rare inherited disease caused by deficient activity of tissue-nonspecific alkaline phosphatase. Many adults with HPP have a high burden of disease, experiencing chronic pain, fatigue, limited mobility, and dental issues, contributing to decreased health-related quality of life (HRQoL). HPP may be treated with the enzyme replacement therapy asfotase alfa though real-world data in adults are limited. This analysis was conducted to assess the clinical effectiveness of asfotase alfa among adults in the Global HPP Registry.

Methods: The Global HPP Registry is an observational, prospective, multinational study. Adults ≥ 18 years of age were included in this analysis if they had serum alkaline phosphatase (ALP) activity below the age- and sex-adjusted reference ranges, and/or ALPL variant(s), and received asfotase alfa for ≥ 6 months. Mobility was assessed with the 6-Minute Walk Test (6MWT), and patient-reported outcomes tools were used to assess pain (Brief Pain Inventory-Short Form), quality of life (36-item Short Form Health Survey, version 2 [SF-36v2]), and disability (Health Assessment Questionnaire-Disability Index) at multiple time points from baseline through Month 36. Data were collected as per usual standard of care; patients may not have contributed data at all time points.

Results: A total of 190 patients met the inclusion criteria. For patients with ≥ 1 follow-up measurement, the mean distance achieved on 6MWT increased from 404 m (range 60-632 m) at baseline (n = 31) to 484 m at Month 12 (range 240-739 m; n = 18) and remained above baseline through Month 36 (n = 7). Improvements in mean self-reported pain severity scores ranged from - 0.72 (95% CI: - 1.23, - 0.21; n = 38) to - 1.13 (95% CI: - 1.76, - 0.51; n = 26) and were observed at all time points. Improvements in the Physical Component Summary score of SF-36v2 were achieved by Month 6 and sustained throughout follow-up. There was a trend toward improvement in the Mental Component Summary score of SF-36v2 at most time points, with considerable fluctuations from Months 12 (n = 28) through 36 (n = 21). The most frequent adverse events were injection site reactions.

Conclusions: Adults with HPP who received asfotase alfa for ≥ 6 months experienced improvements in mobility, physical function, and HRQoL, which were maintained over 3 years of follow-up.

Registration: NCT02306720; EUPAS13514.

Fig. 1

Study population. ALP, alkaline phosphatase; LLN, lower limit of normal

Fig. 2

Cross-sectional analysis of 6MWT over time. (A) Total distance walked; (B) Percent predicted. 6MWT, 6-Minute Walk Test; Nobs, number of observations

Fig. 3

Cross-sectional analysis of self-reported pain measured with BPI-SF over time. (A) Pain severity; (B) Pain interference; and (C) Worst pain in past 24 h. BPI-SF, Brief Pain Inventory–Short Form; Nobs, number of observations

Fig. 4

Cross-sectional analysis of quality of life measured with SF-36v2 over 36 months. (A) RADAR plot showing mean PCS score and its component domains; (B) RADAR plot showing mean MCS score and its component domains. MCS, Mental Component Summary; PCS, Physical Component Summary; SF-36v2, 36-item Short Form Health Survey, version 2

Fig. 5

Cross-sectional analysis of disability measured with HAQ-DI over time. HAQ-DI, Health Assessment Questionnaire–Disability Index; Nobs, number of observations