Introduction

In the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study, cladribine tablets significantly reduced relapse rates and improved findings on magnetic resonance imaging versus placebo in patients with relapsing multiple sclerosis. In the CLARITY Extension study, treatment with cladribine tablets for 2 years followed by placebo for 2 years produced similar clinical benefits to 4 years of cladribine tablets. The objective of this exploratory post hoc analysis was to evaluate long-term disease stability (assessed by the Expanded Disability Status Scale [EDSS] score) after treatment with cladribine tablets.

Methods

Patients enrolled into CLARITY Extension who were previously randomized to cladribine tablets 3.5 mg/kg in the CLARITY study were included in this post hoc analysis. Two treatment groups were investigated—patients randomized to cladribine tablets 3.5 mg/kg in CLARITY and thereafter randomized to placebo in CLARITY Extension (the CP3.5 group) or to cladribine tablets 3.5 mg/kg in CLARITY Extension (the CC7 group). In each treatment group, EDSS scores at 6-month intervals, EDSS score improvement/worsening each year, and time to 3- and 6-month confirmed EDSS progression were assessed from CLARITY baseline over 5 years of follow-up (including a variable bridging interval between studies). All analyses are descriptive, and no statistical comparisons were performed for between-treatment group differences.

Results

The median (95% confidence interval [CI]) EDSS score for patients in the CP3.5 group at 5 years was 2.5 (2.0–3.5) compared with 3.0 (2.5–3.5) at baseline. In the CC7 group, median EDSS score (95% CI) at 5 years was 2.0 (2.0–3.0) compared with 2.5 (2.5–3.0) at baseline. During year 5 for the CP3.5 group, and based on changes in minimum score each year, EDSS score stability was observed in 53.9% of patients, improvement in 21.3%, and worsening in 24.7%. In the CC7 group, EDSS score remained stable in 66.1%, improved in 18.1%, and worsened in 15.8% of patients. Over 70% of patients in both treatment groups did not show 3- or 6-month confirmed EDSS progression at 5 years from CLARITY baseline.

Conclusions

These findings confirm long-term beneficial effects on disability afforded by either the recommended dose of cladribine tablets over 4 years (cumulative dose, 3.5 mg/kg) or a higher cumulative dose.

Trial Registration

ClinicalTrials.gov NCT00213135 (CLARITY); NCT00641537 (CLARITY Extension).

中文翻译：

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用克拉屈滨片剂 3.5 mg/kg 治疗复发性多发性硬化症患者的扩展残疾状态量表评估的长期疾病稳定性：CLARITY 和 CLARITY 扩展研究的探索性事后分析

介绍

在口服治疗多发性硬化症的克拉屈滨片剂 (CLARITY) 研究中，与安慰剂相比，克拉屈滨片剂显着降低了复发率，并改善了复发性多发性硬化症患者的磁共振成像结果。在 CLARITY Extension 研究中，用克拉屈滨片剂治疗 2 年，然后用安慰剂治疗 2 年，其临床获益与服用克拉屈滨片剂 4 年相似。该探索性事后分析的目的是评估克拉屈滨药片治疗后的长期疾病稳定性（通过扩展残疾状态量表 [EDSS] 评分评估）。

方法

纳入 CLARITY Extension 的患者之前在 CLARITY 研究中被随机分配至克拉屈滨片剂 3.5 mg/kg，这些患者被纳入该事后分析。研究了两个治疗组——患者在 CLARITY 中随机分配至 3.5 mg/kg 的克拉屈滨片剂，然后在 CLARITY 扩展组中随机分配至安慰剂组（CP3.5 组）或在 CLARITY 扩展组中随机分配至 3.5 mg/kg 的克拉屈滨片剂（CC7 组）。在每个治疗组中，从 CLARITY 基线超过 5 年的随访（包括可变桥接研究之间的间隔）。所有分析都是描述性的，没有对治疗组间的差异进行统计比较。

结果

5 年时 CP3.5 组患者的 EDSS 评分中位数（95% 置信区间 [CI]）为 2.5 (2.0–3.5)，基线时为 3.0 (2.5–3.5)。在 CC7 组中，5 年时的中位 EDSS 评分 (95% CI) 为 2.0 (2.0–3.0)，而基线时为 2.5 (2.5–3.0)。在 CP3.5 组的第 5 年，根据每年最低分数的变化，观察到 53.9% 的患者 EDSS 评分稳定，21.3% 的患者改善，24.7% 的患者恶化。在 CC7 组中，EDSS 评分在 66.1% 的患者中保持稳定，在 18.1% 的患者中有所改善，在 15.8% 的患者中恶化。两个治疗组中超过 70% 的患者在距 CLARITY 基线 5 年时未显示 3 个月或 6 个月确认的 EDSS 进展。

结论

这些发现证实了 4 年以上推荐剂量的克拉屈滨片剂（累积剂量，3.5 mg/kg）或更高的累积剂量对残疾的长期有益作用。

试用注册

ClinicalTrials.gov NCT00213135（清晰度）；NCT00641537（清晰度扩展）。