Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry.
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
08 Mar 2024
08 Mar 2024
Historique:
received:
12
09
2023
accepted:
19
01
2024
medline:
9
3
2024
pubmed:
9
3
2024
entrez:
8
3
2024
Statut:
epublish
Résumé
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. 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. 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. 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. NCT02306720; EUPAS13514.
Sections du résumé
BACKGROUND
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
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
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
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
BACKGROUND
NCT02306720; EUPAS13514.
Identifiants
pubmed: 38459585
doi: 10.1186/s13023-024-03048-6
pii: 10.1186/s13023-024-03048-6
doi:
Banques de données
ClinicalTrials.gov
['NCT02306720']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109Informations de copyright
© 2024. The Author(s).
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