Abstract
Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal, telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 mo. PROs-Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]-were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 yr [SD: 15.4]; 80% female; 94% White), 49 were evaluable at 3 mo, 44 at 6 mo, and 29 at 12 mo. By month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs 5.8 [P < .0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs 43.0 [P = .001]; anxiety: 57.5 vs 51.5 [P = .0011]; fatigue: 63.3 vs 55.3 [P < .0001]; sleep disturbances: 58.8 vs 54.3 [P = .0099]; ability to participate in social roles and activities: 42.6 vs 47.7 [P = .0012]; and pain interference: 63.8 vs 58.4 [P = .001]), and RAPID3 domain scores (functional status: 2.7 vs 1.1 [P < .0001]; pain tolerance: 6.0 vs 3.2 [P < .0001]; and global health estimate: 5.1 vs 2.7 [P < .0001]). Improvements persisted at month 12. Patients also showed improvements in WPAI:SHP domain scores at month 6 (presenteeism: 39.6% vs 14.1% [P < .0001] and work productivity loss: 41.9% vs 14.1% [P < .0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.