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Efficacy and Safety of CFTR Corrector and Potentiator Combination Therapy in Patients with Cystic Fibrosis for the F508del-CFTR Homozygous Mutation: A Systematic Review and Meta-analysis

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Abstract

Introduction

Cystic fibrosis (CF) is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. The combination of a cystic fibrosis transmembrane conductance regulator (CFTR) corrector and potentiator has provided a benefit by decreasing sweat chloride concentration in CF for the F508del-CFTR homozygous mutation, but it remains controversial in lung function, nutritional status, clinical score and safety.

Methods

The authors performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of combination therapy on lung function, nutritional status, clinical score and safety in CF for the F508del-CFTR homozygous mutation. Web of Science, Cochrane Central Register of Controlled Trials, Medline, and Embase were searched. The registered PROSPERO number was CRD42018085875.

Results

Five RCTs, including a total of 1637 participants with the F508del-CFTR homozygous mutation who accepted CFTR corrector and potentiator combination therapy along with basic treatment were enrolled in this analysis. Primary analysis revealed that combination therapy improved the percent of predicted FEV1 (ppFEV1) (MD 2.38, 1.62–3.15, P < 0.00001), Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score (MD 2.59, 0.96–4.22, P = 0.002) and body-mass index (BMI) (MD 0.21, 0.03–0.39, P = 0.02). In the secondary analysis, combination therapy had no impact on the number of participants reporting adverse events (OR 0.88, 0.58–1.33, P = 0.53), but increased the proportion of discontinued treatments due to adverse events (OR 2.71, 1.3–5.63, P = 0.008).

Conclusions

CFTR corrector and potentiator combination therapy effectively improves lung function, nutritional status and clinical score in CF patients with the F508del-CFTR homozygous mutation, and has an acceptable safety profile.

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Acknowledgements

We thank all the people who participated in the primary randomized controlled trials and the teams who carried them out.

Funding

No funding or sponsorship was received for this study or publication of this article. The article-processing charges were funded by the authors.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authors’ Contribution

Hong-xia Wu and De-yun Cheng initiated and coordinated the study. Xiao-feng Xiong, Min Zhu, Jia Wei and Kai-quan Zhuo were responsible for the data collection and data analysis. Studies were reviewed by De-yun Cheng. Hong-xia Wu wrote the first draft of the manuscript. All the authors were involved in the interpretation of the analyses and gave input to the final manuscript.

Disclosures

Hong-xia Wu, Min Zhu, Xiao-feng Xiong, Jia Wei, Kai-quan Zhuo and De-yun Cheng have nothing to disclose.

Compliance with Ethics Guidelines

The protocols of all enrolled RCTs were reviewed and approved by ethics committees. Informed consents were obtained from all individual participants included in enrolled RCTs.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China

    Hong-xia Wu, Min Zhu, Xiao-feng Xiong & De-yun Cheng

  2. Department of Respiratory Medicine, Chengdu Second People’s Hospital, Chengdu, China

    Jia Wei

  3. Department of Neurosurgery, Suining Municipal Hospital of TCM, Suining, China

    Kai-quan Zhuo

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  1. Hong-xia Wu
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Corresponding author

Correspondence to De-yun Cheng.

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Wu, Hx., Zhu, M., Xiong, Xf. et al. Efficacy and Safety of CFTR Corrector and Potentiator Combination Therapy in Patients with Cystic Fibrosis for the F508del-CFTR Homozygous Mutation: A Systematic Review and Meta-analysis. Adv Ther 36, 451–461 (2019). https://doi.org/10.1007/s12325-018-0860-4

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