Elborn J Stuart, Vataire Anne-Lise, Fukushima Ayako, Aballea Samuel, Khemiri Amine, Moore Curtis, Medic Goran, Hemels Michiel E H
School of Medicine, Dentistry & Biomedical Sciences, Queen׳s University Belfast, Belfast, United Kingdom.
Health Economics and Outcomes Research, Creativ-Ceutical, Paris, France.
Clin Ther. 2016 Oct;38(10):2204-2226. doi: 10.1016/j.clinthera.2016.08.014. Epub 2016 Sep 29.
In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS.
A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates.
Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times.
Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.
在欧洲，目前有4种吸入性抗生素（妥布霉素、多粘菌素甲磺酸钠、氨曲南和左氧氟沙星）被批准用于治疗囊性纤维化（CF）患者的慢性铜绿假单胞菌肺部感染。左氧氟沙星吸入溶液（LIS）是最近被批准用于成年CF患者的吸入性抗生素。进行了一项系统文献综述和贝叶斯网络荟萃分析（NMA），以比较这些吸入性抗生素与LIS的相对短期（4周）和长期（24周）疗效。
于2016年2月16日使用通过OvidSP检索的EMBASE和Medline进行系统文献检索。对所有比较上述任何一种吸入性抗生素且随访时间为4周或24周的随机对照试验进行评估。对以下结局进行NMA：预测的1秒用力呼气容积（FEV%）自基线的相对和绝对百分比变化、铜绿假单胞菌痰液密度变化、CF修订问卷中的呼吸道症状评分、住院情况、额外使用抗生素情况以及研究退出率。
在检索到的685篇文章中，7项独特研究纳入了4周的NMA，9项独特研究纳入了24周的NMA。预计氨曲南在4周时预测的FEV%数值增加最大，而预计LIS在数值上大于多粘菌素甲磺酸钠、妥布霉素吸入溶液（TIS）和妥布霉素吸入粉（TIP）。然而，这些比较的所有95%可信度区间（CrIs）均包含零。在24周时，没有一种治疗方法比LIS显著更有效。与LIS相比，TIS在24周时住院的比值比为1.92（95%CrI，1.01 - 3.30），TIP为2.25（95%CrI，1.01 - 4.34），安慰剂为3.16（95%CrI，1.53 - 5.78），所有这些在统计学上均比LIS差。在所有时间点，所有吸入性抗生素的铜绿假单胞菌痰液密度评分、抗假单胞菌抗生素的额外使用情况以及研究退出率均相当。
基于这项NMA，许多结局的分析未提供显著证据表明其他已批准的吸入性抗生素在治疗CF患者的慢性铜绿假单胞菌肺部感染方面比LIS更有效。这些吸入性抗生素的研究退出率似乎相当。
