In recent years, the serious consequences of Cystic Fibrosis on patients’ health and quality of life have led to the study of new, more effective treatments: CFTR-modulators.

OBJECTIVES: The purpose of this study was to systematically evaluate clinical studies on the four CFTR-modulators approved for the management of cystic fibrosis, to determine the clinical and economic benefits of their use.

METHODS: Initially, all available information on Ivacaftor(VX-770), Lumacaftor(VX-809)/Ivacaftor, Tezacaftor(VX-661)/ Ivacaftor and Elexacaftor(VX-445)/ Tezacaftor/ Ivacaftor) was collected from EMA reports, as well as published phase III, placebo-controlled trials on cystic fibrosis patients. A systematic review/meta-analysis including GRADE was performed to evaluate the clinical benefit of the treatments. Finally, the expenditure associated with cystic fibrosis modulator therapies was estimated.

RESULTS: From a total of 135 clinical studies, seven were found to meet study inclusion criteria. However, only six were finally used for the meta-analysis, as for one formulation only one study met the criteria. Study patients showed a positive response to treatment for all outcomes (Number of pulmonary exacerbations(Pex): Rate Ratio 0.66, %predicted forced expiratory volume in one second(ppFEV₁): Mean difference(MD) 3.07-6.38, Cystic Fibrosis Questionnaire Revised(CFQ-R): MD 2.62-8.11, Body Mass Index(BMI): MD 0.16). The risk of bias for each included study ranged from low to high depending on the criterion and the quality of the data (GRADE) was judged to be moderate or low (2-3). Thus, the results of the meta-analysis cannot be stated with absolute certainty. The estimated cost of therapy per patient per year was lowest with Ivacaftor (VX-770) (€82.199,36) followed by the Lumacaftor (VX-809)/ Ivacaftor combination (€120.104,76).

CONCLUSIONS: The clinical efficacy of the CFTR-modulators seems to be greater than that of the placebo for all outcomes, however more studies are needed to draw safe conclusions. The expenditure associated for treatment with CFTR-modulators was high, but lowest for Ivacaftor(VX-770).