Annals of the American Thoracic Society · 2016
Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis.
СтатьяМногоцентровое исследованиеРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Takada Toshinori, Mikami Ayako, Kitamura Nobutaka, Seyama Kuniaki, Inoue Yoshikazu, Nagai Katsura, Suzuki Masaru, Moriyama Hiroshi, Akasaka Keiichi, Tazawa Ryushi, Hirai Toyohiro, Mishima Michiaki, Hayashida Mie, Hirose Masaki, Sugimoto Chikatoshi, Arai Toru, Hattori Noboru, Watanabe Kentaro, Tamada Tsutomu, Yoshizawa Hirohisa, Akazawa Kohei, Tanaka Takahiro, Yagi Keita, Young Lisa R, McCormack Francis X, Nakata Koh
Аннотация
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.
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.