患有莫尔基奥A综合征的成年亚群的临床结局：艾洛硫酸酯酶α长期扩展研究的结果
Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa.
作者信息
Hughes D, Giugliani R, Guffon N, Jones S A, Mengel K E, Parini R, Matousek R, Hawley S M, Quartel A
机构信息
Royal Free London NHS Foundation Trust and University College London, London, UK.
Medical Genetics Service, Hospital de Clínicas de Porto Alegre and Department of Genetics/Universidade Federal do Rio Grande do Sul and Instituto Nacional de Genética Médica Populacional, Porto Alegre, Brazil.
出版信息
Orphanet J Rare Dis. 2017 May 23;12(1):98. doi: 10.1186/s13023-017-0634-0.
BACKGROUND
This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions). No MorCAP patients underwent orthopedic surgical procedures during the relevant time period. Endurance was assessed by the 6-min walk test (6MWT) and 3-min stair climb test (3MSCT). Activities of daily living (ADLs) were assessed by the MPS Health Assessment Questionnaire (MPS HAQ).
RESULTS
Least squares (LS) mean (SE) 6MWT distances increased by 34.9 (11.7) m (MPP) and 30.5 (10.8) m (ITT) by week 120; LS mean (SE) change in 3MSCT at week 120 was 6.7 (1.8) stairs/min (MPP) and 5.9 (1.7) stairs/min (ITT). MorCAP patients showed no improvement in 6MWT distance or 3MSCT over a similar period of time. Pulmonary function measures remained unchanged in both MOR-005 and MorCAP adults. All MPS HAQ domain scores improved in MOR-005 adults, whereas MorCAP adults had unchanged caregiver assistance and mobility outcomes and worsened self-care outcomes.
CONCLUSIONS
Long-term ERT in adult patients with Morquio A was associated with increased endurance and improvement in performance of ADLs.
TRIAL REGISTRATION
Trial Registration NCT01415427 . Name of registry: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). Registered 8 August 2011, retrospectively registered.
背景
这项事后亚组分析研究了接受艾洛硫酸酯酶α酶替代疗法（ERT）120周的成年莫氏综合征A（黏多糖贮积症IVA）患者的治疗结果。在一项艾洛硫酸酯酶α的开放标签长期扩展研究（根据方案修正[MPP]，n = 32；意向性治疗[ITT]，n = 37；MOR - 005；NCT01415427）中评估的≥18岁患者与来自莫氏综合征A自然史研究（n = 10；MorCAP；NCT00787995）的≥18岁未治疗人群进行了比较，后者有2年的随访。MOR - 005的MPP人群排除了接受过骨科手术或不符合研究方案的患者（定义为错过≥20%的ERT输注）。在相关时间段内，没有MorCAP患者接受骨科手术。通过6分钟步行试验（6MWT）和3分钟爬楼梯试验（3MSCT）评估耐力。通过黏多糖贮积症健康评估问卷（MPS HAQ）评估日常生活活动（ADL）。
结果
到第120周时，最小二乘（LS）均值（SE）的6MWT距离在MPP组增加了34.9（11.7）米，在ITT组增加了30.（10.8）米；第120周时3MSCT的LS均值（SE）变化在MPP组为6.7（1.8）级楼梯/分钟，在ITT组为5.9（1.7）级楼梯/分钟。在相似时间段内，MorCAP患者的6MWT距离或3MSCT没有改善。MOR - 005组和MorCAP组的成年患者肺功能指标均保持不变。MOR - 005组成年患者的所有MPS HAQ领域得分均有所改善，而MorCAP组成年患者的照料者协助和活动能力结果未变，自我照料结果恶化。
结论
成年莫氏综合征A患者的长期ERT与耐力增加和ADL表现改善相关。
试验注册
试验注册号NCT01415427。注册机构名称：BMN 110治疗黏多糖贮积症IVA（莫氏综合征A）患者的长期疗效和安全性扩展研究。2011年8月8日注册，追溯注册。
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