Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
Merck KGaA, Darmstadt, Germany.
Eur J Neurol. 2022 Jul;29(7):2144-2147. doi: 10.1111/ene.15316. Epub 2022 Mar 15.
The aim was to show the application of the prevalence estimator of Expanded Disability Status Scale (EDSS) improvement over time in patients treated with cladribine tablets in the phase III CLARITY/CLARITY extension trials.
Relapsing-remitting multiple sclerosis patients who entered the CLARITY extension study were evaluated. Patients originally randomized in CLARITY to cladribine tablets 3.5 mg/kg and placebo in CLARITY extension (early cladribine [EC]) were compared to patients originally randomized to placebo and then assigned to cladribine tablets 3.5 mg/kg (delayed cladribine [DC]). The EC group was compared to the DC group on the prevalence of EDSS improvement over time and on the cumulative incidence of EDSS improvement. Prevalence of improvement was assessed by a new approach based on the difference of Kaplan-Meier estimators, whilst the incidence of improvement was assessed by standard Kaplan-Meier curves.
A total of 98 patients in the EC group and 244 patients in the DC group were compared. Patients in the EC group showed a significantly higher (p = 0.011) prevalence of improvement at year 2 (EC 21.3%, 95% confidence interval [CI] 13.6-29.3; DC 8.9%, 95% CI 5.5-12.8) and at year 5 (EC 15.7%, 95% CI 8.2-23.7; DC 8.3%, 95% CI 4.5-12.4). The cumulative incidence of improvement was also significantly different (hazard ratio 1.82, 95% CI 1.13-2.94, p = 0.013).
Assessment of the prevalence of EDSS improvement is an alternative outcome to assess if a treatment induces and maintains an improvement over the long term. This estimator was found to be more powerful than the cumulative incidence of improvement to detect a treatment effect of cladribine versus placebo over 5 years.
本研究旨在展示在 CLARITY/CLARITY 扩展试验中接受克拉屈滨片治疗的患者中，随时间推移扩展残疾状况量表（EDSS）改善的发生率估计的应用。
评估进入 CLARITY 扩展研究的复发缓解型多发性硬化症患者。CLARITY 扩展中最初随机分配至克拉屈滨片 3.5mg/kg 和安慰剂的患者（早期克拉屈滨 [EC] 组）与最初随机分配至安慰剂然后分配至克拉屈滨片 3.5mg/kg 的患者（延迟克拉屈滨 [DC] 组）进行比较。EC 组与 DC 组比较了随时间推移 EDSS 改善的发生率以及 EDSS 改善的累积发生率。通过基于 Kaplan-Meier 估计值差异的新方法评估改善的发生率，而通过标准 Kaplan-Meier 曲线评估改善的发生率。
EC 组共 98 例患者，DC 组共 244 例患者进行了比较。EC 组患者在第 2 年（EC 21.3%，95%置信区间 [CI] 13.6-29.3；DC 8.9%，95% CI 5.5-12.8）和第 5 年（EC 15.7%，95% CI 8.2-23.7；DC 8.3%，95% CI 4.5-12.4）时改善的发生率显著更高（p=0.011）。改善的累积发生率也有显著差异（风险比 1.82，95% CI 1.13-2.94，p=0.013）。
评估 EDSS 改善的发生率是评估治疗是否诱导并长期维持改善的替代结局。与累积发生率相比，该估计值在 5 年内检测克拉屈滨与安慰剂的治疗效果更具统计学意义。
