BACKGROUND In multiple sclerosis, impact of treatment on disability progression can be confounded if treatment also reduces relapses. OBJECTIVE To distinguish siponimod's direct effects on disability progression from those on relapses in the EXPAND phase 3 trial. METHODS Three estimands, one based on principal stratum and two on hypothetical scenarios (no relapses, or equal relapses in both treatment arms), were defined to determine the extent to which siponimod's effects on 3- and 6-month confirmed disability progression were independent of on-study relapses. RESULTS Principal stratum analysis estimated that siponimod reduced the risk of 3- and 6-month confirmed disability progression by 14%-20% and 29%-33%, respectively, compared with placebo in non-relapsing patients. In the hypothetical scenarios, risk reductions independent of relapses were 14%-18% and 23% for 3- and 6-month confirmed disability progression, respectively. CONCLUSION By controlling the confounding impact of on-study relapses on confirmed disability progression, these statistical approaches provide a methodological framework to assess treatment effects on disability progression in relapsing and non-relapsing patients. The analyses support that siponimod may be useful for treating secondary progressive multiple sclerosis in patients with or without relapses.

中文翻译：

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Siponimod：解开继发性进行性多发性硬化症的残疾和复发

背景在多发性硬化症中，如果治疗也能减少复发，那么治疗对残疾进展的影响可能会受到混淆。目的在 EXPAND 3 期试验中区分 siponimod 对残疾进展的直接影响与对复发的影响。方研究中复发。结果 主要分层分析估计，与安慰剂相比，辛波莫德在非复发患者中将 3 个月和 6 个月确认的残疾进展风险分别降低了 14%-20% 和 29%-33%。在假设场景中，对于 3 个月和 6 个月确认的残疾进展，独立于复发的风险降低分别为 14%-18% 和 23%。结论通过控制研究中复发对确认的残疾进展的混杂影响，这些统计方法提供了一个方法框架来评估治疗对复发和非复发患者残疾进展的影响。分析支持 siponimod 可用于治疗复发或不复发患者的继发进行性多发性硬化症。这些统计方法提供了一个方法框架来评估治疗对复发和非复发患者残疾进展的影响。分析支持 siponimod 可用于治疗复发或不复发患者的继发进行性多发性硬化症。这些统计方法提供了一个方法框架来评估治疗对复发和非复发患者残疾进展的影响。分析支持 siponimod 可用于治疗复发或不复发患者的继发进行性多发性硬化症。