Physical Function and Health-Related Quality of Life in Adults Treated With Asfotase Alfa for Pediatric-Onset Hypophosphatasia.

Hypophosphatasia (HPP) is a rare, inherited, metabolic disease characterized by tissue-nonspecific alkaline phosphatase deficiency resulting in musculoskeletal and systemic clinical manifestations. This observational study evaluated the effectiveness of enzyme replacement therapy with asfotase alfa on physical function and health-related quality of life (HRQoL) among adults with pediatric-onset HPP who received asfotase alfa for 12 months at a single center (ClinicalTrial.gov no.: NCT03418389). Primary outcomes evaluated physical function with the 6-minute walk test (6MWT), timed up-and-go (TUG) test, Short Physical Performance Battery (SPPB), and handheld dynamometry (HHD). Secondary outcome measures included the Lower Extremity Functional Scale (LEFS), pain prevalence/intensity, and pain medication use; HRQoL was evaluated using the 36-Item Short-Form Health Survey version 2 (SF-36v2). Safety data were collected throughout the study. All 14 patients (11 women) had compound heterozygous gene mutations and ≥1 HPP bone manifestation, including history of ≥1 fracture. Mean (min, max) age was 51 (19 to 78) years. From baseline to 12 months of treatment, median 6MWT distance increased from 267 m to 320 m ( = 13; = 0.023); median TUG test time improved from 14.4 s to 11.3 s ( = 9; = 0.008). Specific components of the SPPB also improved significantly: median 4-m gait speed increased from 0.8 m/s to 1.1 m/s ( = 10; = 0.007) and median repeated chair-rise time improved from 22 s to 13 s ( = 9; = 0.008). LEFS score improved from 24 points to 53 points ( = 10; = 0.002). Improvements in HHD were not clinically significant. SF-36v2 Physical Component Score (PCS) improved after 12 months of treatment ( = 9; = 0.010). Pain level did not change significantly from baseline to 12 months of treatment. There were significant improvements on chair-rise time and SF-36v2 PCS by 3 months, and on TUG test time after 6 months. No new safety signals were identified. These results show the real-world effectiveness of asfotase alfa in improving physical functioning and HRQoL in adults with pediatric-onset HPP. © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.