Adequate tacrolimus concentration for myasthenia gravis treatment
Adequate tacrolimus concentration for myasthenia gravis treatment
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DOI：
10.1111/ene.13189
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发表时间：
2017-02-01
影响因子：
5.1
通讯作者：
Kuwabara, S.
中科院分区：
文献类型：
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作者：
Kanai, T.;Uzawa, A.;Kuwabara, S.
背景和目的日本批准用于重症肌无力(MG)治疗的单次口服他克莫司3 mg/天，被证明可以减少类固醇剂量和抗乙酰胆碱受体(AChR)抗体效价，并改善MG症状。然而，尚未有研究调查他克莫司浓度与其临床疗效之间的关系。方法采用化学发光法测定51例MG患者(抗AChR抗体阳性48例，抗AChR抗体阴性3例，肌特异性酪氨酸激酶抗体阴性3例)服用他克莫司1年以上的血药浓度。结果他克莫司低谷浓度中位数为5.4(2.9~7.6)ng/m L，与病情轻或病情好有关(P=0.0190，r=0.3273)；他克莫司治疗1年后抗乙酰胆碱受体抗体下降(P=0.0170，r=0.3465)。用受试者工作特征曲线将他克莫司的临界值定义为4.8 ng/m L时，他克莫司浓度适中(4.8 ng/m L)的患者抗AChR抗体滴度下降更多，日常生活活动评分改善更多。与低他克莫司浓度相比，他克莫司浓度适中的患者出现轻微症状或病情较好的患者更多。结论适当的他克莫司浓度是MG预后较好的必要条件。
Background and purposeA single, oral dose of 3 mg/day tacrolimus, approved for myasthenia gravis (MG) treatment in Japan, was shown to reduce steroid dose and anti-acetylcholine receptor (AChR) antibody titers as well as to improve MG symptoms. However, no studies have investigated the association between tacrolimus concentration and its clinical efficacy in MG. In this study, we aimed to determine the optimal tacrolimus concentration for MG treatment.MethodsThe trough tacrolimus concentration in 51 patients with MG (positive for anti-AChR antibody, n = 48; negative for anti-AChR and anti-muscle-specific tyrosine kinase antibodies, n = 3) who received 3 mg/day tacrolimus for more than 1 year was measured using a chemiluminescent enzyme immunoassay. The clinical characteristics of patients with MG as well as the dose of prednisolone used before and after tacrolimus treatment were evaluated retrospectively.ResultsThe median trough tacrolimus concentration was 5.4 (range, 2.9-7.6) ng/mL, which was correlated with minimal manifestation or better status' (P = 0.0190, r = 0.3273) and the reduction in anti-AChR antibody 1 year after tacrolimus initiation (P = 0.0170, r = 0.3465). When the cut-off value for tacrolimus was defined as 4.8 ng/mL using a receiver operating characteristic curve, patients with adequate tacrolimus concentration (4.8 ng/mL) showed more reduction in anti-AChR antibody titers and more improvement in MG-related activities in daily life scores. More patients with adequate tacrolimus concentration achieved minimal manifestation or better status' compared with those with low tacrolimus concentration.ConclusionsAn adequate tacrolimus concentration is required for better MG prognosis.