依地酸-beta-羟乙酯治疗莱伯遗传性视神经病变的真实世界临床经验。
Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.
机构信息
Department of Neurology (CBC, OM, TK), Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) (CBC, TK), Munich, Germany; Department of Ophthalmology (BL, CP, FL, GR), University Hospital of the Ludwig-Maximilians-University Munich, Germany; New York Eye and Ear Infirmary of Mount Sinai (RB), New York, New York; Ophthalmology Department (SM), Waikato Hospital, Hamilton, New Zealand; Scheie Eye Institute (MAT), University of Pennsylvania, Philadelphia, Pennsylvania; Institut Català de Retina (LC), Barcelona, Spain; Augenklinik (CF), Universitätsklinikum Giessen, Giessen, Germany; University Hospital Southampton (CAH), Southampton, United Kingdom; McGovern Medical School (JAL), UTHealth, Houston, Texas; Department of Ophthalmology (GLT, KL, SJL), University Hospital and University of Zurich, Zurich, Switzerland; Neuro-ophthalmology Associates (GA), Ankara, Turkey; Manchester Centre for Genomic Medicine (GCMB), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, United Kingdom; Division of Evolution and Genomic Sciences (GCMB), Neuroscience and Mental Health Domain, School of Health Sciences, Faculty of Biology, Medicines and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; Ophthalmology Unit (CD), Hospital de Poniente, El Ejido, Almería, Spain; Save Sight Institute (CLF), University of Sydney, Sydney, Australia; Department of Pediatric Traumatology and Emergency Medicine (JJ), Wroclaw Medical University, Poland; Poland SPEKTRUM Ophthalmology Clinic (JJ), Wroclaw, Poland; University Hospital Ramon y Cajal (FJM-N), IRYCIS, Madrid, Spain; Emory University School of Medicine (NJN), Atlanta Georgia; Nuffield Dept Obstetrics and Gynaecology (JP), University of Oxford, The Women's Centre, Oxford, United Kingdom; Department of Ophthalmology (ES), East Kent Hospitals University Foundation Trust, United Kingdom; Neuro-Ophthalmology Division (PS), University of Colorado School of Medicine, Aurora, Colorado; Department of Neuroinflammation (ATT), Queen Square MS Centre, UCL Institute of Neurology, University College London, London, United Kingdom; Hospital Sant Joan de Déu Barcelona (MV), Barcelona, Spain; Eye Department (ALV), Greenlane Clinical Centre, Auckland, New Zealand; School of Optometry and Vision Sciences (MV), Cardiff University, Cardiff, United Kingdom; Department of Developmental Neurology (MZ), Poznan University of Medical Sciences, Poznan, Poland; Manchester Centre for Clinical Neuroscience (AZ), Salford Royal NHS Foundation Trust, Salford, United Kingdom; Neuro-ophthalmology Unit (MS, XL, GM) Santhera Pharmaceuticals, Pratteln, Switzerland; and Munich Cluster for Systems Neurology (SyNergy) (TK), Munich, Germany.
出版信息
J Neuroophthalmol. 2020 Dec;40(4):558-565. doi: 10.1097/WNO.0000000000001023.
BACKGROUND
Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse.
METHODS
Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed.
RESULTS
At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor.
CONCLUSIONS
These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.
背景
Leber 遗传性视神经病变（LHON）可导致双侧中心视力丧失。在临床试验中，已证明依地苯醌是安全的，并显示出视力提高的趋势，但在真实临床实践中长期有效性的证据很少。
方法
在一项扩展准入计划中，对 111 例接受依地苯醌（900mg/天）治疗的 LHON 患者进行开放性、多中心、回顾性、非对照分析，以评估长期视力和安全性。符合条件的患者具有已证实的线粒体 DNA 突变，并在入组前 1 年内出现症状（最近的眼睛）。根据常规临床实践收集视力和不良事件数据。疗效评估为视力有临床相关恢复（CRR）或临床相关稳定（CRS）的患者比例。在 CRR 的情况下，还评估了恢复的时间和随时间恢复的幅度。
结果
在分析时，87 例患者提供了纵向疗效数据。平均治疗时间为 25.6 个月。46.0%的患者观察到 CRR。通过治疗持续时间的分析表明，恢复的患者比例和恢复的幅度随治疗持续时间的增加而增加。反应者最佳矫正视力的平均增益为 0.72 最小角分辨率对数（logMAR），相当于 ETDRS 图表上超过 7 行。此外，50%的患者在治疗开始时至少有一只眼睛的视力低于 1.0 logMAR，在最后一次观察时成功地将视力保持在这一阈值以下。依地苯醌耐受性良好，大多数不良事件被归类为轻微。
结论
这些数据表明，依地苯醌治疗在恢复丧失的视力和维持良好的残余视力方面具有益处，在真实环境中。这些发现表明，为了最大限度地提高疗效，应尽早开始依地苯醌治疗，并维持 24 个月以上。安全性结果与依地苯醌已知的安全性特征一致。
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