Neuro-otology Unit, Division of Brain Sciences, Charing Cross Hospital Campus, Imperial College London, London, UK.
Ear, Nose and Throat Department, Charing Cross Hospital, London, UK.
Lancet. 2016 Dec 3;388(10061):2753-2762. doi: 10.1016/S0140-6736(16)31461-1. Epub 2016 Nov 17.
Ménière's disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin, the standard treatment for refractory Ménière's disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin.
In this double-blind comparative effectiveness trial, patients aged 18-70 years with refractory unilateral Ménière's disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone (62·5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18-24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529.
Between June 19, 2009, and April 15, 2013, 256 patients with Ménière's disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the final 6 months compared with the 6 months before the first injection (primary outcome) decreased from 19·9 (SD 16·7) to 2·5 (5·8) in the gentamicin group (87% reduction) and from 16·4 (12·5) to 1·6 (3·4) in the methylprednisolone group (90% reduction; mean difference -0·9, 95% CI -3·4 to 1·6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group.
Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménière's disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances.
Ménière's Society and National Institute for Health Research Imperial Biomedical Research Centre.
梅尼埃病的特征是严重的眩晕发作和听力损失。鼓室内庆大霉素是治疗难治性梅尼埃病的标准治疗方法，可减轻眩晕，但会损害前庭功能并可能使听力恶化。我们旨在评估鼓室内给予皮质类固醇甲泼尼龙是否比庆大霉素能减少眩晕。
在这项双盲比较有效性试验中，年龄在 18-70 岁之间的单侧难治性梅尼埃病患者在英国伦敦的查令十字医院和英国莱斯特皇家医院入组。患者按区块设计（1:1）随机分配接受两次鼓室内甲泼尼龙（62.5mg/mL）或庆大霉素（40mg/mL）注射，间隔 2 周，随访 2 年。所有研究者和患者对治疗分配均设盲。主要结局为最后 6 个月（注射后 18-24 个月）与第一次注射前 6 个月相比眩晕频率。分析采用意向治疗人群，并按方案进行。该试验在 ClinicalTrials.gov 注册，编号为 NCT00802529。
2009 年 6 月 19 日至 2013 年 4 月 15 日，对 256 例梅尼埃病患者进行了筛查，其中 60 例患者入组并随机分配：30 例接受庆大霉素，30 例接受甲泼尼龙。在意向治疗分析（即，所有 60 例患者）中，与第一次注射前 6 个月相比，最后 6 个月的眩晕发作次数（主要结局）在庆大霉素组从 19.9（16.7）减少到 2.5（5.8）（减少 87%），在甲泼尼龙组从 16.4（12.5）减少到 1.6（3.4）（减少 90%；平均差异-0.9，95%CI-3.4 至 1.6）。在由未设盲的临床医生评估后，那些眩晕在注射后没有改善的患者（即无反应者）有资格接受由设盲临床医生给予的额外注射（庆大霉素组 8 例，甲泼尼龙组 15 例）。两名无反应者从甲泼尼龙转为庆大霉素。两种药物均耐受性良好，无安全性问题。六名患者各报告 1 例不良事件：庆大霉素组 3 例，甲泼尼龙组 3 例。最常见的不良事件是轻微耳部感染，庆大霉素组 1 例，甲泼尼龙组 2 例。
甲泼尼龙注射是一种非破坏性的、有效的难治性梅尼埃病治疗方法。应根据临床知识和患者情况选择甲泼尼龙和庆大霉素。
梅尼埃病协会和英国国家卫生研究院帝国生物医学研究中心。
