Ford Lisa, Goldberg Jeffrey L, Selan Fred, Greenberg Howard E, Shi Yingqi
Janssen Research & Development, LLC, Titusville, NJ.
Byers Eye Institute, Stanford University, Palo Alto, CA, USA.
Clin Ophthalmol. 2017 May 23;11:983-992. doi: 10.2147/OPTH.S125768. eCollection 2017.
The objective of this study was to analyze clinical patterns of visual field defects (VFDs) reported with topiramate treatment and assess possible mechanism of action (MOA) for antiepileptic drug (AED) associated VFDs.
A comprehensive topiramate database review included preclinical data, sponsor's clinical trials database, postmarketing spontaneous reports, and medical literature. All treatment-emergent adverse events (TEAEs) suggestive of retinal dysfunction/damage were summarized. Relative risk (RR) was computed from topiramate double-blind, placebo-controlled trials (DBPCTs) data.
Preclinical studies and medical literature review suggested that despite sharing gamma-aminobutyric acid (GABA)-ergic MOA with other AEDs, topiramate treatment was not associated with VFDs. TEAEs suggestive of retinal dysfunction/damage were observed in 0.3%-0.7% of adults and pediatric patients with topiramate (N=4,679) versus ≤0.1% with placebo (N=1,834) in DBPCTs for approved indications (epilepsy and migraine prophylaxis); open-label trials (OLTs) and DBPCTs for investigational indications had similar incidence. Overall, 88% TEAEs were mild or moderate in severity. Serious TEAEs were very rare (DBPCTs: 0%; OLTs: ≤0.1%), and most were not treatment limiting, and resolved. The most common visual TEAEs (approved indications) were VFD, scotoma, and optic atrophy. The incidence of TEAEs in DBPCTs (approved and investigational indications) was higher in topiramate-treated (N=9,169) versus placebo-treated patients (N=5,023; 0.36% vs 0.24%), but the RR versus placebo-treated patients was not significant (RR: 1.51 [95% confidence interval: 0.78, 2.91]).
VFDs do not appear to be a class effect for AEDs with GABA-ergic MOA. The RR for VFDs is not significantly different between topiramate and placebo treatment.
本研究旨在分析托吡酯治疗报告的视野缺损（VFD）的临床模式，并评估抗癫痫药物（AED）相关VFD的可能作用机制（MOA）。
对托吡酯综合数据库进行回顾，包括临床前数据、申办者的临床试验数据库、上市后自发报告和医学文献。总结所有提示视网膜功能障碍/损伤的治疗中出现的不良事件（TEAE）。相对风险（RR）根据托吡酯双盲、安慰剂对照试验（DBPCT）数据计算。
临床前研究和医学文献回顾表明，尽管托吡酯与其他AEDs共享γ-氨基丁酸（GABA）能作用机制，但托吡酯治疗与VFD无关。在批准适应症（癫痫和偏头痛预防）的DBPCT中，0.3%-0.7%的接受托吡酯治疗的成人和儿童患者（N=4,679）观察到提示视网膜功能障碍/损伤的TEAE，而安慰剂组（N=1,834）≤0.1%；用于研究适应症的开放标签试验（OLT）和DBPCT的发生率相似。总体而言，88%的TEAE严重程度为轻度或中度。严重TEAE非常罕见（DBPCT：0%；OLT：≤0.1%），且大多数不限制治疗，并可缓解。最常见的视觉TEAE（批准适应症）为VFD、暗点和视神经萎缩。在DBPCT中（批准和研究适应症），接受托吡酯治疗的患者（N=9,169）的TEAE发生率高于接受安慰剂治疗的患者（N=5,023；0.36%对0.24%），但与接受安慰剂治疗的患者相比，RR无显著差异（RR：1.51[95%置信区间：0.78，2.91]）。
VFD似乎不是具有GABA能作用机制的AEDs的类效应。托吡酯和安慰剂治疗之间VFD的RR无显著差异。
