Efficacy and Safety of Three Different Cumulative Doses of Intravenous Methylprednisolone for Moderate to Severe and Active Graves' Orbitopathy
Efficacy and Safety of Three Different Cumulative Doses of Intravenous Methylprednisolone for Moderate to Severe and Active Graves' Orbitopathy
复制标题
DOI：
10.1210/jc.2012-2389
复制
发表时间：
2012-12-01
影响因子：
5.8
通讯作者：
von Arx, G.
中科院分区：
文献类型：
--
作者：
Bartalena, L.;Krassas, G. E.;von Arx, G.
背景：静脉注射糖皮质激素治疗Graves眼病（GO）的最佳剂量尚不明确。方法：我们开展了一项多中心、随机、双盲试验，以确定三种剂量的iv甲基强的松龙在159例中重度和活动性GO患者中的疗效和安全性。患者随机接受累计剂量为2.25、4.98或7.47 g的12周输注。在12周时，由盲眼医生客观评估疗效，由盲眼患者主观评估疗效（使用GO特异性生活质量问卷）。每次就诊时记录不良事件。结果：7.47 g（52%）比4.98 g （35%, P = 0.03）和2.25 g （28%, P = 0.01）更能改善整体视力。与低剂量组相比，高剂量组在眼运动客观测量和临床活动评分方面的改善最大。各组临床活动评分均有下降，最低为2.25 g。7.47 g组的生活质量改善最多，但没有达到统计学意义。在突出眼、睑孔、软组织改变和主观复视评分方面无显著性差异。所有组中均有几例患者出现甲状腺功能障碍视神经病变。正因为如此，在24周的探索性访问中，三组之间的差异不再明显。使用最高剂量时，主要不良事件发生的频率略高，但使用最低剂量时也会发生。在12周GO改善的患者中，7.47组33%，4.98组21%，2.25组40%的患者在24周的探索性随访中糖皮质激素停药后眼病复发。结论：7.47 g剂量较低剂量具有短期优势。然而，这种益处是短暂的，并伴有稍大的毒性。使用累积剂量7.47 g甲基强的松龙比低剂量具有短期优势。这可能表明，在大多数病例中应使用中剂量方案，而高剂量方案应保留给大多数严重的氧化石墨烯病例。[J] .中华内分泌杂志，2012,31(4):444 - 444。
Background: Optimal doses of iv glucocorticoids for Graves' orbitopathy (GO) are undefined.Methods: We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of iv methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit.Results: Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit.Conclusions: The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO. (J Clin Endocrinol Metab 97: 4454-4463, 2012)