Oral siponimod (Mayzent^®), a next-generation, selective sphingosine 1-phosphate receptor (S1PR) 1 and 5 modulator, is approved in several countries for the treatment of secondary progressive multiple sclerosis (SPMS), with specific indications varying between individual countries. In the pivotal EXPAND trial (median duration double-blind treatment 18 months) in a broad spectrum of patients with SPMS, once-daily oral siponimod 2 mg (initial dose titration over 6 days) was significantly more effective than placebo in reducing clinical and MRI-defined outcomes of disease activity and disability progression, including 3-month confirmed disability progression on the Expanded Disability Status Scale (EDSS), and was generally well tolerated in the core phase of the study. These beneficial effects of siponimod appeared to be sustained during up to 5 years of treatment in the ongoing open-label extension phase of EXPAND. The safety profile of siponimod is similar to that of other agents in its class, including adverse events of special interest (i.e. those known to be associated with S1PR modulators). No new safety signals were identified during up to 5 years’ treatment in the open-label extension phase. Albeit further long-term efficacy and safety data from the real-world setting are required to fully define its role, given the paucity of current treatment options and its convenient dosage regimen, siponimod represents an important emerging option for the treatment of adult patients with SPMS with active disease evidenced by relapses or imaging-features of inflammatory activity.

口服西波尼莫德 (Mayzent ^® ) 是一种新一代选择性 1-磷酸鞘氨醇受体 (S1PR) 1 和 5 调节剂，已在多个国家获批用于治疗继发性进行性多发性硬化症 (SPMS)，具体适应症因国家而异。在针对广泛 SPMS 患者的关键 EXPAND 试验（双盲治疗中位持续时间 18 个月）中，每日一次口服西波尼莫德 2 mg（初始剂量滴定超过 6 天）在减少临床和 MRI 方面显着比安慰剂更有效- 疾病活动和残疾进展的明确结果，包括扩展残疾状态量表 (EDSS) 上确认的 3 个月残疾进展，并且在研究的核心阶段通常具有良好的耐受性。在正在进行的 EXPAND 开放标签延伸阶段，辛波尼莫德的这些有益作用似乎在长达 5 年的治疗期间得以持续。辛波尼莫德的安全性与同类其他药物相似，包括特别关注的不良事件（即已知与 S1PR 调节剂相关的不良事件）。在开放标签延伸阶段长达 5 年的治疗期间，没有发现新的安全信号。尽管需要来自现实环境的进一步长期疗效和安全性数据来充分确定其作用，但考虑到当前治疗方案的缺乏及其方便的剂量方案，西波尼莫德代表了治疗 SPMS 成年患者的重要新兴选择患有由复发或炎症活动的影像学特征证明的活动性疾病。