From the Eye Center (S.K., S.P.H., W.A.L.); Clinical Trials Unit (G.I., B.G.), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg; Department of Ophthalmology (F.B.), University Hospital, University of Heidelberg; Department of Neurology (P.A.), Medical Faculty, Heinrich Heine-Universität Düsseldorf; Aalen University of Applied Sciences (J.U., M.W.), Competence Center Vision Research; Pharmacy (M.J.H.), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Department of Ophthalmology (S.W.), Inselspital, University Hospital, University of Bern, Switzerland; and Department of Neurology and National Center for Tumor Diseases (R.D.), Faculty of Medicine, University Hospital Heidelberg, Germany.
Neurol Neuroimmunol Neuroinflamm. 2023 Apr 24;10(4). doi: 10.1212/NXI.0000000000200067. Print 2023 Jul.
Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic neuritis and focused on conversions to multiple sclerosis (MS).
The TONE trial randomized 108 patients with acute optic neuritis but without previously known MS to either 33,000 IU EPO or placebo in conjunction with 1,000 mg methylprednisolone daily for 3 days. After reaching the primary end point at 6 months, we conducted an open-label follow-up 2 years after randomization.
The follow-up was attended by 83 of 103 initially analyzed patients (81%). There were no previously unreported adverse events. The adjusted treatment difference of peripapillary retinal nerve fiber layer atrophy in relation to the fellow eye at baseline was 1.27 µm (95% CI -6.45 to 8.98, = 0.74). The adjusted treatment difference in low-contrast letter acuity was 2.87 on the 2.5% Sloan chart score (95% CI -7.92 to 13.65). Vision-related quality of life was similar in both treatment arms (National Eye Institute Visual Functioning Questionnaire median score [IQR]: 94.0 [88.0 to 96.9] in the EPO and 93.4 [89.5 to 97.4] in the placebo group). The rate of multiple sclerosis-free survival was 38% in the placebo and 53% in the EPO group (hazard ratio: 1.67, 95% CI 0.96 to 2.88, = 0.068).
In line with the results at 6 months, we found neither structural nor functional benefits in the visual system of patients with optic neuritis as a clinically isolated syndrome, 2 years after EPO administration. Although there were fewer early conversions to MS in the EPO group, the difference across the 2-year window was not statistically significant.
This study provides Class II evidence that for patients with acute optic neuritis, EPO as an adjunct to methylprednisolone is well tolerated and does not improve long-term visual outcomes.
The trial was preregistered before commencement at clinicaltrials.gov (NCT01962571).
促红细胞生成素（EPO）是一种候选神经保护药物。我们评估了其作为视神经炎患者甲基强的松龙辅助治疗的长期安全性和疗效，并重点关注多发性硬化症（MS）的转化。
TONE 试验将 108 例急性视神经炎但无已知 MS 的患者随机分为 EPO 组（33000IU）或安慰剂组，联合每日 1000mg 甲基强的松龙治疗 3 天。达到 6 个月的主要终点后，我们在随机分组后 2 年进行了开放标签随访。
在最初分析的 103 例患者中有 83 例（81%）接受了随访。没有报告以前未报告的不良事件。与对侧眼相比，基线时视盘周围视网膜神经纤维层萎缩的调整治疗差异为 1.27µm（95%CI-6.45 至 8.98， = 0.74）。2.5%Sloan 图表评分的低对比度字母视力的调整治疗差异为 2.87（95%CI-7.92 至 13.65）。在视觉相关生活质量方面，两种治疗组相似（国家眼科研究所视觉功能问卷中位数评分[IQR]：EPO 组为 94.0[88.0 至 96.9]，安慰剂组为 93.4[89.5 至 97.4]）。安慰剂组和 EPO 组多发性硬化症无生存的发生率分别为 38%和 53%（风险比：1.67，95%CI 0.96 至 2.88， = 0.068）。
与 6 个月时的结果一致，我们发现视神经炎患者在接受 EPO 治疗 2 年后，无论是在视觉系统的结构还是功能方面，均未显示出获益。尽管 EPO 组早期向 MS 的转化较少，但在 2 年的时间窗内，差异无统计学意义。
本研究提供了 II 级证据，对于急性视神经炎患者，EPO 作为甲基强的松龙的辅助治疗是可以耐受的，并且不会改善长期的视觉结果。
该试验在 clinicaltrials.gov 上预先注册（NCT01962571）。
Zotero 插件
