Dahir Kathryn M, Ing Steven W, Deal Chad, Messali Andrew, Bates Toby, Rush Eric T
Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
Division of Endocrinology, Diabetes, and Metabolism, Wexner Medical Center, Ohio State University, Columbus, OH 43210, United States.
JBMR Plus. 2024 May 7;8(8):ziae062. doi: 10.1093/jbmrpl/ziae062. eCollection 2024 Aug.
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 [ .0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs 43.0 [ .001]; anxiety: 57.5 vs 51.5 [ .0011]; fatigue: 63.3 vs 55.3 [ .0001]; sleep disturbances: 58.8 vs 54.3 [ .0099]; ability to participate in social roles and activities: 42.6 vs 47.7 [ .0012]; and pain interference: 63.8 vs 58.4 [ .001]), and RAPID3 domain scores (functional status: 2.7 vs 1.1 [ .0001]; pain tolerance: 6.0 vs 3.2 [ .0001]; and global health estimate: 5.1 vs 2.7 [ .0001]). Improvements persisted at month 12. Patients also showed improvements in WPAI:SHP domain scores at month 6 (presenteeism: 39.6% vs 14.1% [ .0001] and work productivity loss: 41.9% vs 14.1% [ .0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.
低磷酸酯酶症（HPP）是一种罕见的遗传性代谢紊乱疾病，由组织非特异性碱性磷酸酶活性不足引起。本研究评估了阿法骨化醇治疗对儿童期发病的成人HPP患者报告结局（PROs）的影响。对纳入患者支持项目的符合条件的个体进行了一项基于电话的纵向调查。在研究开始时（阿法骨化醇开始治疗前）以及3、6和12个月后进行访谈。在每个时间点评估PROs——患者健康问卷-9 [PHQ-9]、工作生产力和活动障碍问卷：特定健康问题 [WPAI:SHP]、患者报告结局测量信息系统29 [PROMIS-29] 和患者指数数据常规评估3 [RAPID3]。进行了适当的统计测试以评估分数变化。在50名登记患者中（平均年龄：46岁 [标准差：15.4]；80%为女性；94%为白人），49名在3个月时可评估，44名在6个月时可评估，29名在12个月时可评估。到第3个月时，PHQ-9分数（10.6对5.8 [P = 0.0001]）、PROMIS-29领域分数（总体身体功能：38.0对43.0 [P = 0.001]；焦虑：57.5对51.5 [P = 0.0011]；疲劳：63.3对55.3 [P = 0.0001]；睡眠障碍：58.8对54.3 [P = 0.0099]；参与社会角色和活动的能力：42.6对47.7 [P = 0.0012]；以及疼痛干扰：63.8对58.4 [P = 0.001]）和RAPID3领域分数（功能状态：2.7对1.1 [P = 0.0001]；疼痛耐受性：6.0对3.2 [P = 0.0001]；以及总体健康评估：5.1对2.7 [P = 0.0001]）与基线相比有统计学显著改善。在第12个月时改善持续存在。患者在第6个月时WPAI:SHP领域分数也有改善（出勤主义：39.6%对14.1% [P = 0.0001] 和工作生产力损失：41.9%对14.1% [P = 0.0001]）。阿法骨化醇治疗与多个领域的生活质量改善相关。
