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Abstract：
OBJECTIVE: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).
METHODS: Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.
RESULTS: As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.
CONCLUSIONS: Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
METHODS: Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.
RESULTS: As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.
CONCLUSIONS: Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
摘要：
目标：注册管理机构和国际卓越数据库（STRIDE）的战略定位正在进行中，国际,在临床实践中，具有无义突变Duchenne肌营养不良症（nmDMD）的个体在现实世界中使用ataluren的多中心注册。这份更新的中期报告(数据截止日期：2022年1月31日)，描述了STRIDE患者特征和ataluren安全数据，以及在国际神经肌肉研究小组（CINRG）Duchenne自然史研究（DNHS）中，ATALREN+标准护理（SoC）在STRIDE中的有效性与仅SoC的有效性。
方法：患者从入组后随访至少5年或直至研究退出。进行倾向评分匹配以识别在确定的疾病进展预测因子方面具有可比性的STRIDE和CINRGDNHS患者。
结果：截至2022年1月31日，共有来自14个国家的307名患者入选。首次症状和基因诊断时的平均（标准偏差[SD]）年龄分别为2.9（1.7）岁和4.5（3.7）岁，分别。Ataluren暴露的平均持续时间（SD）为1671（56.8）天。Ataluren具有良好的安全性；大多数因治疗引起的不良事件为轻度或中度，与ataluren无关。Kaplan-Meier分析表明，ataluren加上SoC显着延迟了4年的步行丧失年龄（p<0.0001）和下降到％-预测的强迫肺活量<60％和<50％的年龄1.8年（p=0.0021）和2.3年（p=0.0207），分别,与单独的SoC相比。
结论：长期，ataluren加SoC的真实世界治疗延迟了nmDMD患者的几个疾病进展里程碑。NCT02369731；注册日期：2015年2月24日。
方法：患者从入组后随访至少5年或直至研究退出。进行倾向评分匹配以识别在确定的疾病进展预测因子方面具有可比性的STRIDE和CINRGDNHS患者。
结果：截至2022年1月31日，共有来自14个国家的307名患者入选。首次症状和基因诊断时的平均（标准偏差[SD]）年龄分别为2.9（1.7）岁和4.5（3.7）岁，分别。Ataluren暴露的平均持续时间（SD）为1671（56.8）天。Ataluren具有良好的安全性；大多数因治疗引起的不良事件为轻度或中度，与ataluren无关。Kaplan-Meier分析表明，ataluren加上SoC显着延迟了4年的步行丧失年龄（p<0.0001）和下降到％-预测的强迫肺活量<60％和<50％的年龄1.8年（p=0.0021）和2.3年（p=0.0207），分别,与单独的SoC相比。
结论：长期，ataluren加SoC的真实世界治疗延迟了nmDMD患者的几个疾病进展里程碑。NCT02369731；注册日期：2015年2月24日。
