Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Curr Med Res Opin. 2020 Jun;36(6):921-928. doi: 10.1080/03007995.2020.1756234. Epub 2020 May 12.
Macitentan, a novel dual endothelin receptor antagonist, was approved for the treatment of pulmonary arterial hypertension (PAH) in Japan. However, long-term effects in Japanese patients of macitentan are currently unavailable. This study sought to assess the long-term efficacy and safety of macitentan in Japanese patients with PAH. In this multicenter, open-label, clinical extension study (JapicCTI-121986), efficacy was evaluated based on the change from baseline at 24, 48, 72, 96 and 120-week in the 6-minute walk distance (6MWD), World Health Organization (WHO) functional class, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. In addition, the time to a hospitalization related to PAH and a morbidity/mortality event was determined. As for safety, the incidence of adverse events and changes in laboratory data and vital signs were assessed. Macitentan was administered at a once-daily dose of 10 mg in 30 PAH patients with a median treatment period of 2.4 years (range, 229-1037 days). The improvements in 6MWD, WHO functional class and NT-pro-BNP at week 24 were maintained throughout the long-term follow-up. Hospitalization related to PAH occurred in 2 patients. Levels of liver enzyme and hemoglobin remained unchanged throughout the study period. This study suggests that the long-term use of macitentan is well tolerated and effective in Japanese patients with PAH. We concluded that macitentan can be a possible approach to reduce morbidity/mortality in Japanese PAH patients.
马西替坦是一种新型双重内皮素受体拮抗剂，已在日本获批用于治疗肺动脉高压（PAH）。然而，目前尚无马西替坦在日本 PAH 患者中的长期疗效数据。本研究旨在评估马西替坦治疗日本 PAH 患者的长期疗效和安全性。在这项多中心、开放标签、临床拓展研究（JapicCTI-121986）中，根据 24、48、72、96 和 120 周时 6 分钟步行距离（6MWD）、世界卫生组织（WHO）功能分级和血清 N 末端脑利钠肽前体（NT-pro-BNP）水平的基线变化评估疗效。此外，还确定了与 PAH 相关的住院时间和发病率/死亡率事件的时间。安全性方面，评估了不良事件的发生率以及实验室数据和生命体征的变化。30 例 PAH 患者接受马西替坦 10mg 每日 1 次治疗，中位治疗时间为 2.4 年（范围：229-1037 天）。24 周时 6MWD、WHO 功能分级和 NT-pro-BNP 的改善在长期随访中得以维持。2 例患者因 PAH 住院。研究期间，肝酶和血红蛋白水平保持不变。本研究提示，长期使用马西替坦治疗日本 PAH 患者耐受良好且疗效持久。我们得出结论，马西替坦可能是降低日本 PAH 患者发病率/死亡率的一种方法。
