Pagano Gennaro, Trundell Dylan, Simuni Tanya, Pavese Nicola, Marek Kenneth, Postuma Ronald B, Shariati Nima, Monnet Annabelle, Moore Emma, Davies Evan W, Svoboda Hanno, Pross Nathalie, Bonni Azad, Nikolcheva Tania
Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery; and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.
University of Exeter Medical School, London, UK.
NPJ Parkinsons Dis. 2025 Jul 1;11(1):193. doi: 10.1038/s41531-025-01041-9.
The use of symptomatic medications represents a challenge for clinical trials of novel medicines designed to slow Parkinson's disease progression. A time-to-event (TTE) approach using a defined motor progression milestone may mitigate the confounding effect of symptomatic therapy on the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). This analysis uses prasinezumab- and placebo-treated groups from the PASADENA study to evaluate the impact of symptomatic medications on treatment effects by comparing a TTE approach to a change-from-baseline approach with and without censoring the population upon starting symptomatic therapy. While the TTE approach yielded consistent hazard ratios between censored and non-censored analyses, the estimated difference between treatment arms using the change-from-baseline approach was lower without censoring than with censoring, suggesting a potential masking of prasinezumab treatment effects by symptomatic therapy. Thus, the TTE approach may mitigate the potential confounding effect of symptomatic therapy on MDS-UPDRS Part III.
对于旨在延缓帕金森病进展的新型药物临床试验而言,使用对症药物是一项挑战。采用定义明确的运动进展里程碑的事件发生时间(TTE)方法,可能会减轻对症治疗对运动障碍协会赞助的统一帕金森病评定量表修订版(MDS-UPDRS)的混杂影响。本分析使用帕西尼单抗治疗组和安慰剂治疗组的帕萨迪纳研究数据,通过比较TTE方法与基线变化方法(在开始对症治疗时对人群进行删失和不删失)来评估对症药物对治疗效果的影响。虽然TTE方法在删失分析和非删失分析之间产生了一致的风险比,但使用基线变化方法时,未进行删失处理的治疗组之间的估计差异低于进行删失处理的情况,这表明对症治疗可能会掩盖帕西尼单抗的治疗效果。因此,TTE方法可能会减轻对症治疗对MDS-UPDRS第三部分的潜在混杂影响。