Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O'Leary C, Ratcliffe S, Nováková I, Zapletalova O, Piková J, Ambler Z
Royal Berkshire and Battle Hospitals NHS Trust, London Road, Reading, Berkshire RG1 5AN, UK.
Neurol Res. 2010 Jun;32(5):451-9. doi: 10.1179/016164109X12590518685660. Epub 2010 Mar 19.
Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients.
To compare Sativex with placebo in relieving symptoms of spasticity due to MS.
A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy.
The primary endpoint was a spasticity 0-10 numeric rating scale (NRS). Intention-to-treat (ITT) analysis showed a non-significant improvement in NRS score, in favor of Sativex. The per protocol (PP) population (79% of subjects) change in NRS score and responder analyses (> or =30% improvement from baseline) were both significantly superior for Sativex, compared with placebo: -1.3 versus -0.8 points (change from baseline, p=0.035); and 36% versus 24% (responders, p=0.040). These were supported by the time to response (ITT: p=0.068; PP: p=0.025) analyses, carer global impression of change assessment (p=0.013) and timed 10-meter walk (p=0.042). Among the subjects who achieved a > or =30% response in spasticity with Sativex, 98, 94 and 73% reported improvements of 10, 20 and 30%, respectively, at least once during the first 4 weeks of treatment. Sativex was generally well tolerated, with most adverse events reported being mild-to-moderate in severity.
The 0-10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status.
肌肉痉挛在多发性硬化症（MS）中很常见，超过60%的患者会出现。
比较Sativex与安慰剂在缓解MS所致痉挛症状方面的效果。
一项为期15周的多中心、双盲、随机、安慰剂对照、平行组研究，纳入337例当前抗痉挛治疗未能完全缓解痉挛症状的MS患者。
主要终点是痉挛0 - 10数字评定量表（NRS）。意向性分析（ITT）显示NRS评分虽有改善但无统计学意义，Sativex组更优。符合方案（PP）人群（占受试者的79%）的NRS评分变化及反应者分析（较基线改善≥30%）均显示，与安慰剂相比，Sativex组显著更优：-1.3分对-0.8分（较基线变化，p = 0.035）；反应者比例分别为36%对24%（p = 0.040）。这些结果得到了反应时间分析（ITT：p = 0.068；PP：p = 0.025）、护理人员对变化的整体印象评估（p = 0.013）和10米定时步行（p = 0.042）的支持。在使用Sativex使痉挛改善≥30%的受试者中，分别有98%、94%和73%的人在治疗的前4周内至少有一次报告改善了10%、20%和30%。Sativex总体耐受性良好，报告的大多数不良事件为轻至中度。
0 - 10 NRS和反应者PP分析表明，对于晚期MS和严重痉挛患者，Sativex治疗可显著降低难治性痉挛。治疗第1个4周内观察到的反应似乎有助于预测反应者/非反应者状态。
