Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis
Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis
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DOI：
10.1513/annalsats.201605-335oc
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发表时间：
2016-11-01
影响因子：
8.3
通讯作者：
Nakata, Koh
中科院分区：
文献类型：
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作者：
Takada, Toshinori;Mikami, Ayako;Nakata, Koh
基本原理：一项随机对照临床试验显示，西罗莫司可稳定接受12个月治疗的淋巴管平滑肌瘤病（LAM）患者的肺功能;然而，停药后治疗前肺功能下降表明，需要持续暴露以抑制疾病进展。目的：阐明西罗莫司长期治疗亚洲LAM患者的持久性和耐受性。方法：我们在日本9个研究中心的63名LAM女性患者中进行了一项单组、开放标签、药物启动的西罗莫司安全性和疗效研究。受试者接受西罗莫司2年的剂量调整，以维持谷血水平为5 - 15 ng/ml.Measurements和主要结果：五十二名受试者（82.5%）完成了试验，平均药物依从性超过80%的整体研究期间。在治疗的最初6个月，不良事件的数量最多，但在整个2年的研究期间，不良事件的发生频率持续下降。在1,549例不良事件中，27例被归类为严重事件，包括3例患者的可逆性西罗莫司肺炎。30名患者（48%）出现新的高胆固醇血症; 10名患者出现小红细胞症; 33名患者体重减轻; 5名患者血压升高，需要治疗。FEV1，FVC，和生活质量参数是稳定的，在整个研究队列在研究期间，但基线至2年的改善肺功能发生在亚组的患者有既往病史的乳糜胸.Conclusions：虽然长期西罗莫司治疗的亚洲患者LAM与大量的不良事件，包括三次发作的肺炎，大多数患者完成了2年的疗程，良好的药物依从性和稳定的生活质量和肺功能。
Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period; however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression.Objectives:To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM.Methods:We conducted a single-arm, open-label, investigator-initiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml.Measurements and Main Results:Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in 30 patients (48%); microcytosis in 10 patients; loss of body weight in 33 patients; and increase in blood pressure that required treatment in 5 patients. FEV1, FVC, and quality-of-life parameters were stable in the overall study cohort during the study period, but baseline to 2-year improvements in lung function occurred in the subset of patients with a prior history of chylothorax.Conclusions:Although long-term sirolimus treatment of Asian patients with LAM was associated with a large number of adverse events, including three episodes of pneumonitis, most patients completed the 2-year course of medication with good drug compliance and stable quality of life and lung function.