Kitamura Nobutaka, Seyama Kuniaki, Inoue Yoshikazu, Nagai Katsura, Suzuki Masaru, Moriyama Hiroshi, Takada Toshinori, Tazawa Ryushi, Hirai Toyohiro, Mishima Michiaki, Hayashida Mie, Hirose Masaki, Arai Toru, Sugimoto Chikatoshi, Hattori Noboru, Watanabe Kentaro, Tamada Tsutomu, Akazawa Kohei, Tanaka Takahiro, Nakata Koh
Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
Department of Respiratory Medicine, School of Medicine, Juntendo University, Tokyo, Japan.
Pharmacoepidemiol Drug Saf. 2017 Oct;26(10):1182-1189. doi: 10.1002/pds.4259. Epub 2017 Jul 28.
Lymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial.
Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5 to 15 ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses.
The most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9 months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (<14.5 g/dL) showed significantly higher incidence than those with high Hb (≥14.5 g/dL, P < .01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study.
Baseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.
淋巴管平滑肌瘤病是一种由异常平滑肌样细胞增殖引起的罕见肺部疾病，通常发生在绝经前女性中。西罗莫司现在是治疗淋巴管平滑肌瘤病的一线药物。西罗莫司引起的口腔炎是治疗期间最常见的不良事件。为了确定危险因素，我们使用多中心长期西罗莫司试验的数据，研究了口腔炎发病率与患者背景数据和治疗参数之间的关联。
受试者接受西罗莫司治疗2年，剂量根据维持谷血浓度5至15 ng/mL进行调整。口腔炎的发病率与基线人口统计学、临床特征以及纵向数据的变化相关。通过单因素和多因素分析评估基线时的危险因素。
最常见的不良事件是口腔炎，到9个月时累积发生率达到88.9%，高于肾移植后患者的报告发生率。口腔炎事件的复发、持续时间和严重程度在患者之间各不相同。我们发现血红蛋白（Hb）低（<14.5 g/dL）的患者比Hb高（≥14.5 g/dL）的患者发病率显著更高（P <.01）。在Hb水平保持不变的情况下，口腔炎发病率的累积率与平均红细胞体积的降低显著相关；因此，在研究期间患者的红细胞计数增加。
基线Hb水平和治疗期间平均红细胞体积的降低与口腔炎的发病率相关。
