Abstract：
OBJECTIVE: Eteplirsen, approved in the US for patients with Duchenne muscular dystrophy (DMD) with exon 51 skip-amenable variants, is associated with attenuated ambulatory/pulmonary decline versus DMD natural history (NH). We report overall survival in a US cohort receiving eteplirsen and contextualize these outcomes versus DMD NH.
METHODS: US patients with DMD receiving eteplirsen were followed through a patient support program, with data collected on ages at eteplirsen initiation and death/end of follow-up. Individual DMD NH data were extracted by digitizing Kaplan-Meier (KM) curves from published systematic and targeted literature reviews. Overall survival age was analyzed using KM curves and contextualized with DMD NH survival curves; subanalyses considered age groups and duration of eteplirsen exposure. Overall survival time from treatment initiation was also evaluated.
RESULTS: A total of 579 eteplirsen-treated patients were included. During a total follow-up of 2119 person-years, median survival age was 32.8 years. DMD NH survival curves extracted from four publications (follow-up for 1224 DMD NH controls) showed overall pooled median survival age of 27.4 years. Eteplirsen-treated patients had significantly longer survival from treatment initiation versus age-matched controls (age-adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.98; p < .05). Longer treatment exposure was associated with improved survival (HR, 0.15; 95% CI, 0.05-0.41; p < .001). Comparisons using different DMD NH cohorts to address common risks of bias yielded consistent findings.
CONCLUSIONS: Data suggest eteplirsen may prolong survival in patients with DMD across a wide age range. As more data become available, the impact of eteplirsen on survival will be further elucidated.
METHODS: US patients with DMD receiving eteplirsen were followed through a patient support program, with data collected on ages at eteplirsen initiation and death/end of follow-up. Individual DMD NH data were extracted by digitizing Kaplan-Meier (KM) curves from published systematic and targeted literature reviews. Overall survival age was analyzed using KM curves and contextualized with DMD NH survival curves; subanalyses considered age groups and duration of eteplirsen exposure. Overall survival time from treatment initiation was also evaluated.
RESULTS: A total of 579 eteplirsen-treated patients were included. During a total follow-up of 2119 person-years, median survival age was 32.8 years. DMD NH survival curves extracted from four publications (follow-up for 1224 DMD NH controls) showed overall pooled median survival age of 27.4 years. Eteplirsen-treated patients had significantly longer survival from treatment initiation versus age-matched controls (age-adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.98; p < .05). Longer treatment exposure was associated with improved survival (HR, 0.15; 95% CI, 0.05-0.41; p < .001). Comparisons using different DMD NH cohorts to address common risks of bias yielded consistent findings.
CONCLUSIONS: Data suggest eteplirsen may prolong survival in patients with DMD across a wide age range. As more data become available, the impact of eteplirsen on survival will be further elucidated.
摘要：
目标：Eteplirsen，在美国批准用于杜兴氏肌营养不良症（DMD）患者，其外显子51可跳跃变异，与DMD自然史（NH）相比，与减弱的卧床/肺下降有关。我们报告了接受eteplirsen的美国队列的总体生存率，并将这些结果与DMDNH进行了背景分析。
方法：接受eteplirsen的美国DMD患者通过患者支持计划进行随访，收集了eteplirsen开始和死亡/随访结束时的年龄数据。通过将Kaplan-Meier（KM）曲线数字化，从已发表的系统和有针对性的文献综述中提取各个DMDNH数据。使用KM曲线分析总生存年龄，并结合DMDNH生存曲线进行分析；亚分析考虑了年龄组和eteplirsen暴露的持续时间。还评估了从治疗开始的总生存时间。
结果：共纳入579例接受eteplirsen治疗的患者。在总共2119人年的随访中，中位生存年龄为32.8岁.从四个出版物(1224个DMDNH对照的随访)中提取的DMDNH存活曲线显示总体合并中位生存年龄为27.4岁。与年龄匹配的对照相比，Eteplirsen治疗的患者从治疗开始的生存期明显更长（年龄调整后的风险比[HR]，0.65；95%置信区间[CI]，0.44-0.98；p<0.05）。更长的治疗暴露与提高生存率相关(HR，0.15；95%CI，0.05-0.41；p<.001）。使用不同的DMDNH队列进行比较，以解决偏见的常见风险，得出一致的结论。
结论：数据表明eteplirsen可以延长DMD患者的生存期。随着更多的数据可用，eteplirsen对生存的影响将进一步阐明.
方法：接受eteplirsen的美国DMD患者通过患者支持计划进行随访，收集了eteplirsen开始和死亡/随访结束时的年龄数据。通过将Kaplan-Meier（KM）曲线数字化，从已发表的系统和有针对性的文献综述中提取各个DMDNH数据。使用KM曲线分析总生存年龄，并结合DMDNH生存曲线进行分析；亚分析考虑了年龄组和eteplirsen暴露的持续时间。还评估了从治疗开始的总生存时间。
结果：共纳入579例接受eteplirsen治疗的患者。在总共2119人年的随访中，中位生存年龄为32.8岁.从四个出版物(1224个DMDNH对照的随访)中提取的DMDNH存活曲线显示总体合并中位生存年龄为27.4岁。与年龄匹配的对照相比，Eteplirsen治疗的患者从治疗开始的生存期明显更长（年龄调整后的风险比[HR]，0.65；95%置信区间[CI]，0.44-0.98；p<0.05）。更长的治疗暴露与提高生存率相关(HR，0.15；95%CI，0.05-0.41；p<.001）。使用不同的DMDNH队列进行比较，以解决偏见的常见风险，得出一致的结论。
结论：数据表明eteplirsen可以延长DMD患者的生存期。随着更多的数据可用，eteplirsen对生存的影响将进一步阐明.
