Ackermans Nathalie, Taylor Carolyn, Tam Roger, Carruthers Robert, Kolind Shannon, Kang Heejun, Freedman Mark S, Li David Kb, Traboulsee Anthony L
University of British Columbia, Department of Medicine (Neurology), Canada.
University of British Columbia, Department of Statistics, Canada.
Mult Scler J Exp Transl Clin. 2019 Feb 16;5(1):2055217318823796. doi: 10.1177/2055217318823796. eCollection 2019 Jan-Mar.
The objective of this paper is to evaluate potential dose-dependent adverse effects of gadolinium-based contrast agents (GBCAs) on MS progression.
Outcomes from a cohort of 612 secondary progressive MS (SPMS) patients, enrolled in a two-year, placebo-controlled (negative) trial assessing the efficacy of MBP8298, were acquired. Patients received one to four (infrequent cohort; IFR) or 5-11 (frequent cohort; FR) GBCA injections between week 4 and week 104. The primary outcome was the change in Expanded Disability Status Scale (EDSS) and time to confirmed EDSS progression. Secondary outcomes included the changes in the Multiple Sclerosis Functional Composite (MSFC), Timed 25-Foot Walk (T25FW), 9-Hole-Peg Test (9HPT), and Paced Auditory Serial Addition Test (PASAT) from baseline to week 104.
The 512 IFR and 100 FR participants showed no differences in baseline demographics or disease history. The mean change from baseline to week 104 in EDSS was +0.21 (IFR) and +0.13 (FR); MSFC -0.38 (IFR) and -0.14 (FR); T25FW +1.28 (IFR) and +0.55 (FR); 9HPT -0.06 (IFR) and -0.08 (FR); and PASAT +0.22 (IFR) and +0.20 (FR). The FR to IFR progression hazard ratio equaled 0.68 ( = 0.09). There were no significant differences in any of the outcomes between the two cohorts.
There were no differences in the disability progression measures between the two cohorts, indicating that gadolinium does not result in greater clinical worsening in SPMS after a two-year period.
本文旨在评估钆基造影剂（GBCAs）对多发性硬化症（MS）进展的潜在剂量依赖性不良反应。
收集了612例继发进展型MS（SPMS）患者的研究结果，这些患者参与了一项为期两年的、评估MBP8298疗效的安慰剂对照（阴性）试验。患者在第4周和第104周之间接受了1至4次（不频繁组；IFR）或5至11次（频繁组；FR）GBCA注射。主要结局是扩展残疾状态量表（EDSS）的变化以及确认EDSS进展的时间。次要结局包括从基线到第104周多发性硬化症功能综合评分（MSFC）、25英尺计时步行试验（T25FW）、9孔插钉试验（9HPT）和听觉序列加法试验（PASAT）的变化。
512例IFR参与者和100例FR参与者在基线人口统计学或疾病史方面无差异。从基线到第104周，EDSS的平均变化在IFR组为+0.21，在FR组为+0.13；MSFC在IFR组为-0.38，在FR组为-0.14；T25FW在IFR组为+1.28，在FR组为+0.55；9HPT在IFR组为-0.06，在FR组为-0.08；PASAT在IFR组为+0.22，在FR组为+0.20。FR组与IFR组的进展风险比为0.68（=0.09）。两组在任何结局方面均无显著差异。
两组在残疾进展测量方面无差异，表明钆在两年期后不会导致SPMS患者出现更严重的临床恶化。
