MS Center for Innovations in Care, Missouri Baptist Medical Center, St Louis, MO 63131, USA.
Int J Clin Pract. 2011 Aug;65(8):887-95. doi: 10.1111/j.1742-1241.2011.02721.x. Epub 2011 Jun 16.
Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral treatment approved by the US Food and Drug Administration for the treatment of relapsing forms of multiple sclerosis (MS). The aim of this review was to provide a concise, comprehensive overview of the clinically relevant mechanism of action, efficacy and safety information available for fingolimod. Key data were derived from two international, Phase III, double-blind, randomised trials (TRANSFORMS and FREEDOMS) performed over 12 and 24 months, respectively, which evaluated fingolimod 0.5 and 1.25 mg daily in 1703 patients with relapsing forms of MS. In TRANSFORMS, there was a 52% reduction in the annualised relapse rate (ARR) with fingolimod 0.5 mg vs. 30 μg intramuscular interferon beta-1a (0.16 vs. 0.33; p < 0.001) at 1 year. In FREEDOMS, there was a 55% decrease in ARR at 2 years with fingolimod 0.5 mg vs. placebo (0.18 vs. 0.40; p < 0.001). Risk of disability progression, confirmed at 3 months, was also reduced by 30% over the 2-year study period with fingolimod vs. placebo (p = 0.02). Significantly fewer new or enlarged lesions on T(2) -weighted images were seen in both studies (TRANSFORMS, p = 0.002 vs. interferon beta-1a at 1 year; FREEDOMS, p < 0.001 vs. placebo at 2 years). Overall, fingolimod 0.5 mg was well tolerated by patients. Transient, generally asymptomatic bradycardia and infrequent atrioventricular block were seen with the administration of the first dose. Macular oedema and serious infections occurred infrequently. Reversible, asymptomatic elevations of liver enzymes could also occur. As the first approved oral disease-modifying treatment, fingolimod offers patients a convenient alternative to regular self-injection for the treatment of relapsing forms of MS. In addition to high efficacy with a relatively acceptable safety profile, fingolimod provides a therapy with a new mechanism of action.
芬戈莫德是一种鞘氨醇 1-磷酸受体调节剂，是美国食品和药物管理局（FDA）批准的第一种用于治疗多发性硬化症（MS）复发型的口服治疗药物。本文旨在对芬戈莫德的临床相关作用机制、疗效和安全性信息进行简要、全面的概述。关键数据源自两项为期 12 个月和 24 个月的国际、III 期、双盲、随机临床试验（TRANSFORMS 和 FREEDOMS），共纳入 1703 例复发型 MS 患者，评估每日口服 0.5mg 和 1.25mg 芬戈莫德的疗效。TRANSFORMS 研究中，与肌内注射干扰素β-1a（30μg，0.16 年复发率）相比，0.5mg 芬戈莫德可使年复发率（ARR）降低 52%（0.16 vs. 0.33；p<0.001），1 年时达到统计学意义。FREEDOMS 研究中，0.5mg 芬戈莫德组在 2 年时 ARR 降低 55%（0.18 vs. 0.40；p<0.001），与安慰剂相比差异具有统计学意义。在整个 2 年研究期间，与安慰剂相比，使用芬戈莫德可使确认的残疾进展风险降低 30%（p=0.02）。在这两项研究中，新出现或扩大的 T2 加权影像病变均显著减少（TRANSFORMS 研究中，与干扰素β-1a 相比，p=0.002；FREEDOMS 研究中，与安慰剂相比，p<0.001）。总体而言，患者对 0.5mg 芬戈莫德的耐受性良好。首次用药时会出现短暂、通常无症状的心动过缓和偶发的房室传导阻滞。黄斑水肿和严重感染的发生率较低。也可能出现可逆的、无症状的肝酶升高。作为首个获批的口服疾病修正治疗药物，芬戈莫德为接受复发型 MS 治疗的患者提供了一种方便的替代常规自我注射的治疗选择。除了具有较高的疗效和相对可接受的安全性特征外，芬戈莫德还提供了一种具有全新作用机制的治疗选择。
