BACKGROUND As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics. METHODS A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations. RESULTS Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively). CONCLUSIONS There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in CF people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.

中文翻译：

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粘菌素钠 (Colobreathe®) 的长期安全性研究：来自英国囊性纤维化登记处的调查结果

背景 作为欧洲风险管理计划的一部分，进行了一项长期观察性研究，以监测吸入用粘菌素钠干粉 (CMS-DPI) 与其他吸入性抗生素相比的安全性。方法从 2014-2018 年英国囊性纤维化登记处 (UKCFR) 确定了 CMS-DPI 患者队列和匹配队列。主要结果是一个复合终点，定义为不良事件 (AE) 或新的囊性纤维化 (CF) 并发症。其他结果包括肺部恶化和治疗中断。结果 在 CMS-DPI 和比较组的 1466 和 3503 名患者中，分别有 82.7% 和 79.4% 的患者出现 AE。最常见的新 CF 并发症包括骨质减少、CF 相关糖尿病和肝酶升高。主要结局的调整后事件发生率 (ERR) 为 1。25 (95% 置信区间 [CI]: 1.18-1.33, p<0.001)。排除新的 CF 并发症后，队列之间没有差异（ERR=1.04，95% CI：0.79-1.38，p=0.785）。肺部恶化在 CMS-DPI 和比较组中很常见（分别为 78.0% 和 79.9% 的患者），调整后的 ERR 为 1.02（95% CI：0.95-1.10，p=0.523）。CMS-DPI 和妥布霉素吸入粉末比较组的停药率相似（分别为 37.8% 和 39.8% 的患者）。结论 CMS-DPI 和对照组之间的不良事件发生率没有差异。CMS-DPI 的安全性与其他吸入抗生素相似，支持其在 CF 患者中的长期安全性。