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重症肌无力的免疫抑制疗法。

Immunosuppressive therapies in myasthenia gravis.

机构信息

Duke University Medical Center, Durham, NC 27705, USA.

出版信息

Autoimmunity. 2010 Aug;43(5-6):428-35. doi: 10.3109/08916930903518107.

Abstract

Immunosuppression is the mainstay of treatment for myasthenia gravis (MG). In this paper, we review the mechanisms of action and clinical application of corticosteroids and different classes of immunosuppressive drugs that are currently used in MG patients, and present the results of their use in more than 1000 patients with MG seen at our two centers. Immunosuppressive treatment was considered along with, or as an alternative to thymectomy in MG patients with disabling weakness, not adequately controlled with anticholinesterase drugs. Overall, 82% of our patients received immunosuppressants for at least 1 year, with frequencies varying according to disease severity, from 93-95% of those with thymoma or MuSK antibodies to 72% in ocular myasthenia. Prednisone was used in the great majority of patients, azathioprine was the first-choice immunosuppressant; mycophenolate mofetil and cyclosporine were used as second-choice agents. All clinical forms of MG benefited from immunosuppression: the rate of remission or minimal manifestations ranged from 85% in ocular myasthenia to 47% in thymoma-associated disease. Treatment was ultimately withdrawn in nearly 20% of anti-AChR positive early-onset patients, but in only 7% of thymoma cases. The risk of complications appears to depend on drug dosage, treatment duration, and patient characteristics, the highest rate of serious side effects (20%) having been found in late-onset MG and the lowest (4%) in early-onset disease. Although nonspecific, current immunosuppressive treatment is highly effective in most MG patients. Lack of randomized evidence, the need for prolonged administration, and unwanted effects are still relevant limitations to its use.

摘要

免疫抑制是重症肌无力(MG)治疗的主要方法。本文综述了目前用于 MG 患者的皮质类固醇和不同类别的免疫抑制剂的作用机制和临床应用,并介绍了我们在两个中心诊治的 1000 多例 MG 患者使用这些药物的结果。免疫抑制治疗被认为是与胸腺切除术相结合或作为替代方法,用于伴有严重肌无力的 MG 患者,这些患者对抗胆碱酯酶药物的治疗反应不佳。总体而言,我们 82%的患者接受了至少 1 年的免疫抑制剂治疗,根据疾病严重程度,其频率有所不同,从胸腺瘤或 MuSK 抗体患者的 93-95%到眼肌型的 72%。大多数患者使用泼尼松,硫唑嘌呤是首选的免疫抑制剂;霉酚酸酯和环孢素被用作二线药物。所有类型的 MG 均从免疫抑制治疗中获益:缓解率或最小表现率从眼肌型的 85%到胸腺瘤相关疾病的 47%不等。近 20%的抗 AChR 阳性早发性患者最终停用了治疗,但在胸腺瘤患者中只有 7%。并发症的风险似乎取决于药物剂量、治疗持续时间和患者特征,最高的严重副作用发生率(20%)见于迟发性 MG,最低的(4%)见于早发性疾病。尽管免疫抑制治疗不是特异性的,但在大多数 MG 患者中具有高度疗效。缺乏随机证据、需要长期给药和不良反应仍然是其应用的相关限制。

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