Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5C1, Canada.
University of Kansas Medical Center, Kansas City, KS 66160, USA.
J Comp Eff Res. 2020 Oct;9(14):973-984. doi: 10.2217/cer-2020-0095. Epub 2020 Aug 27.
Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] ≥300-<400 or <400 m). Meta-analyses examined 6MWD change from baseline to week 48. Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2-34.1) m, p = 0.0473; ≥300-<400 m (n = 143), +43.9 (18.2-69.6) m, p = 0.0008; <400 m (n = 216), +27.7 (6.4-49.0) m, p = 0.0109. These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD ≥300-<400 m (the ambulatory transition phase), thereby informing future trial design.
评估非终止密码子突变型杜氏肌营养不良症（nmDMD）患者中氨苯砜的总体疗效证据。将两项完成的氨苯砜治疗 nmDMD 的随机对照试验（ClinicalTrials.gov：NCT00592553；NCT01826487）的数据合并，以评估意向治疗（ITT）人群和两个患者亚组（基线 6 分钟步行距离[6MWD]≥300-<400 或 <400 m）。Meta 分析检测了从基线到 48 周时的 6MWD 变化。在所有三项 Meta 分析中，氨苯砜与安慰剂相比，6MWD 变化均有统计学意义的差异。最小二乘均数差值（95%CI）：ITT（n=342），+17.2（0.2-34.1）m，p=0.0473；≥300-<400 m（n=143），+43.9（18.2-69.6）m，p=0.0008；<400 m（n=216），+27.7（6.4-49.0）m，p=0.0109。这些 Meta 分析支持了氨苯砜在 48 周内相对于安慰剂减缓 nmDMD 患者疾病进展的先前证据。在基线 6MWD≥300-<400 m 的患者中（运动能力过渡阶段），治疗获益最为明显，这为未来的临床试验设计提供了信息。
