Comparison of inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis: systematic literature review and network meta-analysis

PURPOSE: 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. METHODS: 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 (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates. RESULTS: 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 FEV1% 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 FEV1% 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. IMPLICATIONS: 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

Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England

Jie Meng,1 Johanna Lister,1 Anne-Lise Vataire,2 Roman Casciano,1 Jerome Dinet2 1Analytica Laser, London, UK; 2Ipsen Pharma, Boulogne-Billancourt, France Purpose: The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy. Methods: We developed a partitioned-survival model with three health states to assess the cost-effectiveness of cabozantinib and its comparators. The model time horizon was 30 years. Efficacy and safety data were derived from pivotal clinical trials (METEOR: NCT01865747, CheckMate025: NCT01668784, and AXIS: NCT00678392). METEOR data were used for a direct comparison of cabozantinib and everolimus. Cabozantinib and nivolumab were compared indirectly, whereas equal efficacy for axitinib and everolimus was assumed based on a previously published expert opinion. For all efficacy endpoints, the best-fitting log-logistic or fractional polynomial curves were used to estimate outcomes. Utilities were converted from the 5-level EQ-5D version instrument applied during the METEOR study for specific health states. Reductions in utility scores due to adverse events were applied. English costs (eg, drug prices) and resource use (eg, visit to consultant) data were used. Results: The total treatment cost was estimated to be 84,136 Great British Pounds (GBP) per patient treated with cabozantinib. The health gains were 2.26 life-years (LYs) and 1.78 quality-adjusted LYs (QALYs). The incremental cost-effectiveness ratios (ICERs) versus axitinib and everolimus were 98,967 GBP/QALY and 137,450 GBP/QALY, respectively. Cabozantinib was less costly and more effective than nivolumab; the incremental cost was −6,742 GBP and the QALY difference was 0.18. Conclusion: Treatment with cabozantinib was more effective than treatment with axitinib or everolimus but was associated with higher total costs. When compared with nivolumab, cabozantinib represents an efficient option with nominally better efficacy and lower costs. Keywords: incremental cost-effectiveness ratio, health economic analysis, health care costs, kidney cancer, targeted therap