Cazzola Mario, Calzetta Luigino, Rogliani Paola, Matera Maria Gabriella
Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Ther Adv Drug Saf. 2017 Jan;8(1):17-30. doi: 10.1177/2042098616667304. Epub 2016 Sep 16.
Tiotropium is now delivered two different inhaler devices: the original Handihaler 18 μg once daily, which uses a powder formulation; and the newer Respimat Soft Mist Inhaler (SMI) 5 μg once daily. It has been questioned whether the two devices can be assumed to have the same safety profile, although the TIOSPIR trial showed that tiotropium when administered Respimat SMI 5 μg is not less safe than Handihaler 18 μg. Therefore, we have carried out a safety evaluation of tiotropium Handihaler 18 µg tiotropium Respimat SMI 5 µg and 2.5 µg, systematic review and network meta-analysis of the currently available clinical evidence. The results of our meta-analysis with an extremely large number of patients analysed demonstrate that the safety profile of tiotropium HandiHaler is generally superior to that of tiotropium Respimat SMI, although no statistical difference was detected between these two devices. However, the SUCRA analysis favoured tiotropium Respimat SMI with regards to serious adverse events (AEs). We do not believe that using Respimat SMI rather that HandiHaler exposes patients to higher risks of real AEs. Rather, we believe that there may be a different cardiovascular (CV) response to muscarinic receptors blockage in individual patients. Therefore, it will be essential to make all possible efforts to proactively identify patients at increased risk of CV AEs when treated with tiotropium or another antimuscarinic drug.
最初的Handihaler，每日一次，每次18微克，使用粉末制剂；以及较新的Respimat软雾吸入器（SMI），每日一次，每次5微克。尽管TIOSPIR试验表明，使用Respimat SMI 5微克的噻托溴铵安全性不低于Handihaler 18微克，但人们质疑这两种装置是否具有相同的安全性。因此，我们对18微克Handihaler噻托溴铵、5微克和2.5微克Respimat SMI噻托溴铵进行了安全性评估，对现有临床证据进行了系统评价和网络荟萃分析。我们对大量患者进行的荟萃分析结果表明，Handihaler噻托溴铵的安全性总体上优于Respimat SMI噻托溴铵，尽管这两种装置之间未检测到统计学差异。然而，SUCRA分析在严重不良事件（AE）方面更倾向于Respimat SMI噻托溴铵。我们认为，使用Respimat SMI而非Handihaler不会使患者面临更高的实际AE风险。相反，我们认为个体患者对毒蕈碱受体阻断可能存在不同的心血管（CV）反应。因此，在使用噻托溴铵或其他抗毒蕈碱药物治疗时，必须尽一切可能积极识别CV AE风险增加的患者。
