Rodriguez Santana Idaira, Frank Samuel, Doherty Maria, Willock Rosa, Hamilton Jamie, Hubberstey Hayley, Stanley Cath, Vetter Louise, Winkelmann Michaela, Dolmetsch Ricardo E, Li Nanxin, Ratsch Sarah, Ali Talaha M
HCD Economics (IRS, MD, RW); Harvard Medical School/Beth Israel Deaconess Medical Center (SF); CHDI Foundation (JH); Huntington's Disease Youth Organization (HDYO) (HH); Huntington's Disease Association (CS); Huntington's Disease Society of America (LV); Deutsche Huntington-Hilfe e.V (MW); and UniQure (RED, NL, SR, TMA), Inc, Lexington, MA.
Neurol Clin Pract. 2022 Dec;12(6):e172-e180. doi: 10.1212/CPJ.0000000000200095.
Huntington disease (HD) is a rare, inherited, and highly complex neurodegenerative disorder with no currently approved disease-modifying treatments. We investigated the effect of HD on health-related quality of life and other patient-reported outcomes in the Huntington's Disease Burden of Illness (HDBOI) study.
The HDBOI study is a retrospective, cross-sectional study conducted between September 2020 and May 2021 in France, Germany, Italy, Spain, the United Kingdom, and the United States. People with symptomatic onset HD (PwHD) were recruited by their HD-treating physicians and categorized as early (ES), mid (MS), or advanced stage (AS) HD. Physicians provided sociodemographic and clinical information from the participant's medical records in electronic case report forms (eCRF); participants or their proxies completed online Patient Public Involvement Engagement questionnaires (PPIE-P). Patient-reported outcomes included the 5-level EQ-5D version (EQ-5D-5L), Short-Form-(SF)-36 v2 (and SF-6-Dimension [SF-6D] utility), Huntington Quality of Life Instrument (H-QoL-I), and the Work Productivity and Activity Impairment Specific Health Problem. All outcomes were summarized using descriptive statistics, and differences between disease stages were assessed by Kruskal-Wallis tests.
A total of 2,094 PwHD were enrolled with completed eCRFs (100%) and PPIE-P forms (n = 482, 23%). Participants' mean age was 47.3 years; they were generally evenly distributed across countries, with the majority being ES (40%) followed by MS (33%) and LS (26%). The mean EQ-5D-5L (n = 336) utility score was 0.59 (SD, 0.27), with the highest mean utility scores [SD] in ES (0.72 [0.22]) followed by MS (0.62 [0.18]) and AS (0.37 [0.30]), < 0.001. The mean SF-6D score (n = 482) was 0.57 (SD, 0.10), with mean values decreasing with advanced disease (ES, 0.61; MS, 0.56; AS, 0.50, < 0.001). H-QoL-I mean scores (n = 482) also worsened with more advanced disease, from 0.58 for ES to 0.49 for MS and 0.37 for AS, < 0.001. Impairment in daily activities and in work productivity also increased with more advanced disease. Overall proxy respondents reported on average worse outcomes than PwHD (self-reported) across all outcomes and disease stages suggesting a possible unawareness of deficits by PwHD.
The HDBOI study provides new insights into the characteristics and humanistic burden of PwHD and offers a meaningful contribution to this underserved research area.
亨廷顿病（HD）是一种罕见的、遗传性的且高度复杂的神经退行性疾病，目前尚无获批的疾病修饰治疗方法。在亨廷顿病疾病负担（HDBOI）研究中，我们调查了HD对健康相关生活质量及其他患者报告结局的影响。
HDBOI研究是一项回顾性横断面研究，于2020年9月至2021年5月在法国、德国、意大利、西班牙、英国和美国开展。有症状性HD发作的患者（PwHD）由其HD治疗医生招募，并分为早期（ES）、中期（MS）或晚期（AS）HD。医生通过电子病例报告表（eCRF）从参与者的病历中提供社会人口学和临床信息；参与者或其代理人完成在线患者公众参与问卷（PPIE-P）。患者报告的结局包括5级EQ-5D版本（EQ-5D-5L）、简明健康调查简表（SF-36）v2（以及SF-6维度[SF-6D]效用）、亨廷顿生活质量量表（H-QoL-I）以及工作效率和活动障碍特定健康问题。所有结局均使用描述性统计进行总结，并通过Kruskal-Wallis检验评估疾病阶段之间的差异。
共纳入2094例PwHD，其eCRF均已完成（100%），PPIE-P表格也已完成（n = 482，23%）。参与者的平均年龄为47.3岁；他们在各国的分布总体较为均匀，大多数为ES（40%），其次是MS（33%）和LS（26%）。EQ-5D-5L（n = 336）效用评分的平均值为0.59（标准差，0.27），ES组的平均效用评分最高[标准差]（0.72[0.22]），其次是MS组（0.62[0.18]）和AS组（0.37[0.30]），P < 0.001。SF-6D评分（n = 482）的平均值为0.57（标准差，0.10），其平均值随着疾病进展而降低（ES组为0.61；MS组为0.56；AS组为0.50，P < 0.001）。H-QoL-I评分的平均值（n = 482）也随着疾病进展而恶化，从ES组的0.58降至MS组的0.49和AS组的0.37，P < 0.001。日常活动和工作效率的损害也随着疾病进展而增加。总体而言，代理人报告的所有结局和疾病阶段的结果平均比PwHD（自我报告）更差，这表明PwHD可能未意识到自身的缺陷。
HDBOI研究为PwHD的特征和人文负担提供了新的见解，并为这个研究不足的领域做出了有意义的贡献。
