Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis
Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis
复制标题
西罗莫司治疗淋巴管平滑肌瘤病患者的长期疗效和安全性
DOI：
10.1186/s13023-019-1178-2
复制
发表时间：
2019-08-20
影响因子：
3.7
通讯作者：
Xu, Kai-Feng
中科院分区：
文献类型：
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作者：
Hu, Siqi;Wu, Xiuxiu;Xu, Kai-Feng
西罗莫司已被证实对淋巴管平滑肌瘤病（LAM）有效，这是一种罕见的女性多系统肿瘤性疾病。然而，西罗莫司治疗LAM的长期效果在很大程度上是未知的。我们的目的是分析西罗莫司治疗LAM的长期疗效和安全性，并进行4年随访。方法对142例服用西罗莫司1-4年的散发LAM患者进行回顾性分析。用于分析的变量包括西罗莫司治疗开始前后的肺功能检查、动脉血气分析、6分钟步行距离（6 MWD）、圣乔治呼吸道评分（SGRQ）和血清血管内皮生长因子-D（VEGF-D）水平。计算这些变量的变化率（斜率），并分析不良事件。结果142例患者中，122例获得随访，83例获得随访，60例获得随访，32例获得随访，随访时间分别为1、2、3、4年。与治疗前相比，西罗莫司治疗改善了第1秒用力呼气容积（FEV 1）和用力肺活量（FVC）的变化率（FEV 1，- 10 +/- 15 vs. - 178 +/- 36 ml/y，P < 0.001和FVC，54 +/- 22 vs.- 72 +/- 68 ml/y，P < 0.05）。与基线测量值相比，观察到第1年FEV 1显著改善;第1-2年FVC显著改善;第1-3年动脉血氧水平、6 MWD和SGRQ显著改善;第1-4年VEGF-D显著改善。总体而言，在4年观察期间，所有变量均稳定或改善。与西罗莫司相关的不良事件为轻度。结论西罗莫司治疗LAM可有效改善或稳定患者的肺功能、氧水平、运动能力和生活质量，持续时间长达4年。VEGF-D在治疗后4年内维持在较低水平。与西罗莫司相关的不良事件为轻度。
Background Sirolimus has been confirmed to be effective for lymphangioleiomyomatosis (LAM), a rare multisystem neoplastic disease in women. The long-term effects of sirolimus treatment for LAM, however, are largely unknown. We aimed to analyze the long-term efficacy and safety of sirolimus therapy for LAM with 4-year follow-up. Methods In total, 142 sporadic LAM patients who took sirolimus for 1-4 years were retrospectively enrolled for this analysis. The variables used for analysis included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), St. George's Respiratory Questionnaires (SGRQ) and serum vascular endothelial growth factor-D (VEGF-D) levels before and after the initiation of sirolimus therapy. The rates of change (slope) in those variables were calculated, and adverse events were also analyzed. Results In total, 122, 83, 60 and 32 patients out of 142 were followed for 1, 2, 3 and 4 years respectively. Sirolimus treatment improved the change rate in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) compared with the data before treatment (FEV1, - 10 +/- 15 vs. - 178 +/- 36 ml/y, P < 0.001 and FVC, 54 +/- 22 vs.-72 +/- 68 ml/y, P < 0.05). In comparison to the baseline measurements, significant improvements were observed in FEV1 at the first year; FVC at 1-2 years; arterial oxygen levels, 6MWD, and SGRQ at 1-3 years; and VEGF-D at 1-4 years. Overall, all variables stabilized or improved during the 4 years of observation. Adverse events related to sirolimus were mild. Conclusion Sirolimus therapy is effective at improving or stabilizing pulmonary function, oxygen levels, exercise capacity, and quality of life in patients with LAM for up to 4 years. VEGF-D is maintained at a lower level for 4 years after treatment. Adverse events related to sirolimus were mild.