Department of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.
Mult Scler. 2018 Oct;24(12):1594-1604. doi: 10.1177/1352458517727603. Epub 2017 Sep 5.
In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS).
To assess the safety and efficacy of cladribine treatment in a 2-year Extension study.
In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained.
A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension.
Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.
在为期 2 年的 CLARITY 研究中，克拉屈滨片显著改善了复发缓解型多发性硬化症（MS）患者的临床和磁共振成像（MRI）结局（与安慰剂相比）。
评估克拉屈滨治疗在为期 2 年的扩展研究中的安全性和疗效。
在这项为期 2 年的扩展研究中，CLARITY 中的安慰剂接受者接受了克拉屈滨 3.5mg/kg；克拉屈滨接受者以 2:1 的比例重新随机分配至克拉屈滨 3.5mg/kg 或安慰剂组，保持盲法。
共有 806 名患者接受了治疗。各组之间的不良事件发生率通常相似，但克拉屈滨组的淋巴细胞减少症 3 级及以上发生率高于安慰剂组（4 级淋巴细胞减少症罕见发生）。在 CLARITY 中接受克拉屈滨 3.5mg/kg 治疗且在扩展研究中出现淋巴细胞减少症 3 级及以上的患者中，>90%接受克拉屈滨 3.5mg/kg 治疗且所有接受安慰剂治疗的患者在研究结束时恢复至 0-1 级。CLARITY 中的克拉屈滨治疗产生的疗效改善在扩展研究中接受安慰剂治疗的患者中得以维持；在 CLARITY 中接受克拉屈滨 3.5mg/kg 治疗的患者中，当在扩展研究中给予安慰剂时，约 75%的患者保持无复发状态。
克拉屈滨片治疗 2 年，随后 2 年给予安慰剂治疗，产生了与 4 年克拉屈滨治疗相似的持久临床获益，且严重淋巴细胞减少症或临床恶化的风险较低。在该试验环境下，初始 2 年治疗后，进一步用克拉屈滨片治疗并未明显改善疗效。
