Endocrine Abstracts

Hypophosphatasia (HPP) is a rare, inherited, metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. A heterogeneous presentation in adults includes musculoskeletal symptoms, impaired physical function, and reduced health-related quality of life (HRQoL). Asfotase alfa is the only approved treatment for pediatric-onset HPP. We evaluated, in a real-world setting, the long-term effectiveness of asfotase alfa on physical function and HRQoL among adults with pediatric-onset HPP (NCT03418389). Data were analyzed from adults who had pediatric-onset HPP, were aged >18 years, and received care at the Orthopedic Institute of the Julius-Maximilians-University of Würzburg. They had received asfotase alfa for ≥ 24 months. Physical function evaluation included the 6-Minute Walk Test (6MWT), Timed Up-and-Go (TUG) test, Lower Extremity Functional Scale (LEFS), and Short Physical Performance Battery (SPPB). HRQoL was assessed with the 36-item Short-Form Health Survey, version 2 (SF-36v2); prevalence and intensity of pain were evaluated. Safety data were collected throughout the study. The study included 14 (11 women, 3 men) patients, with a median (min, max) age of 53 (20, 78) years for women and 46 (19, 57) years for men at asfotase alfatreatment initiation. All 14 patients had compound heterozygous ALPL gene variants, ≥ 1 HPP bone manifestation, and history of ≥ 1 fracture. We previously reported on the score changes for each tool from baseline to 12 months; here we report changes from 12–24 months. Improvements on treatment were observed over the first 12 months and maintained over another 12 months. Median (min, max) distance, according to 6MWT, was similar at 12 (320 [0, 605] m) and 24 (316 [60, 600] m) months (n = 13; P = 0.115). A slight increase in median time to complete the TUG test from 11.3s–13.75s was not statistically significant (n = 7; P = 0.382). Specific SPPB component results were stable. Slight decreases seen in median 4m usual gait speed from 1.12 m/s–1.02 m/s (n = 9; P = 0.61) and in median repeated chair rise time from 12.53 s–12.48 s (n = 8; P = 0.398) were not statistically significant. Improvements in LEFS (n = 10) and SF-36v2 Physical Component Summary (n = 9) scores were observed early at 3 and 6 months and remained stable over 24 months. Changes in pain level (n = 5) were variable between 12 and 24 months. No new safety signals were identified. These data suggest adults who have pediatric-onset HPP treated with asfotase alfa in real-world settings have marked improvements in clinical and functional outcomes, which were observed early and sustained over 24 months of treatment.