Peng Yuyao, Jiang Fei, Zhou Ran, Jin Wanlin, Li Yi, Duan Weiwei, Xu Liqun, Yang Huan
Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Jul 12;17:2281-2289. doi: 10.2147/NDT.S319500. eCollection 2021.
Tacrolimus has been recommended as an effective immunosuppressant for patients with myasthenia gravis (MG), while the high price, variable bioavailability, and narrow therapeutic window restrict its clinical application. Wuzhi capsule (WZC) could improve tacrolimus blood concentration by inhibiting the metabolism of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). There are few studies focused on the coadministration of WZC and tacrolimus in autoimmune diseases. This study was aimed at quantifying the efficacy and safety of coadministration of WZC and tacrolimus in adult Chinese patients with MG.
In this retrospective study, 122 patients with MG on tacrolimus were enrolled. The initial tacrolimus dose was 2 mg/d. Patients with standard initial tacrolimus concentration were classified into group A (standard-dose group). Those failed to reach target concentration were divided into group B (high-dose group) and group C (co-administering WZC group), according to treatment adjustment of increasing tacrolimus dose and co-administration of WZC, respectively. A logistic analysis was used to identify factors associated with clinical outcome. Adverse drug reactions (ADRs) were recorded for safety analysis.
The tacrolimus concentration after coadministration of WZC was remarkably increased. It was higher compared with simply increasing the tacrolimus dose (<0.001). The multivariate logistic analysis indicated that the baseline quantitative MG score was a predictive factor for clinical outcomes (OR=0.189; 95% CI 0.082-0.436; <0.001). Fourteen patients (11.5%) reported ADRs after tacrolimus therapy. ADRs incidence was not related to WZC coadministration.
The coadministration of WZC and tacrolimus can substantially elevate the tacrolimus concentration. It is a safe and economic treatment for adult Chinese patients with MG. Patients with a worse disease condition tend to present a better clinical outcome after tacrolimus therapy.
他克莫司已被推荐作为重症肌无力（MG）患者的一种有效免疫抑制剂，但其高昂的价格、可变的生物利用度和狭窄的治疗窗限制了其临床应用。五酯胶囊（WZC）可通过抑制细胞色素P450 3A（CYP3A）和P-糖蛋白（P-gp）的代谢来提高他克莫司血药浓度。目前针对WZC与他克莫司联合应用于自身免疫性疾病的研究较少。本研究旨在量化WZC与他克莫司联合应用于成年中国MG患者的疗效和安全性。
在这项回顾性研究中，纳入了122例接受他克莫司治疗的MG患者。他克莫司初始剂量为2mg/d。初始他克莫司浓度达标的患者被分为A组（标准剂量组）。未达到目标浓度的患者根据增加他克莫司剂量和联合应用WZC的治疗调整，分别分为B组（高剂量组）和C组（联合应用WZC组）。采用逻辑分析来确定与临床结局相关的因素。记录药物不良反应（ADR）进行安全性分析。
联合应用WZC后他克莫司浓度显著升高。与单纯增加他克莫司剂量相比更高（<0.001）。多因素逻辑分析表明，基线MG定量评分是临床结局的预测因素（OR=0.189；95%CI 0.082-0.436；<0.001）。14例患者（11.5%）在他克莫司治疗后报告了ADR。ADR发生率与联合应用WZC无关。
WZC与他克莫司联合应用可显著提高他克莫司浓度。对于成年中国MG患者，这是一种安全且经济的治疗方法。病情较差的患者在他克莫司治疗后往往有更好的临床结局。
