Update on Clinical Outcomes of Highly Effective Modulator Therapy - 05/11/22

Doi : 10.1016/j.ccm.2022.06.009

Alex H. Gifford, MD, FCCP ^a,^b,^⁎ , Jennifer L. Taylor-Cousar, MD, MSCS, ATSF ^c,^d, Jane C. Davies, MD, MB, ChB, MRCP, MRCPCH ^e,^f, Paul McNally, MD, MB, BCh, BAO ^g,^h
^a Division of Pulmonary, Critical Care, and Sleep Medicine, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Bolwell Building 6174, Cleveland, OH 44106, USA
^b Rainbow Babies and Children’s Hospital, Cleveland, OH, USA
^c Department of Internal Medicine, National Jewish Medical Center, Denver, CO, USA
^d Department of Pediatrics, National Jewish Medical Center, Denver, CO, USA
^e National Heart and Lung Institute, Imperial College London, England, United Kingdom
^f Royal Brompton & Harefield Hospital, Guys & St Thomas’ Trust, London, United Kingdom
^g Department of Paediatrics, RCSI University of Medicine and Health Sciences, Dublin, Ireland
^h Cystic Fibrosis Center, Children’s Health Ireland, Dublin, Ireland

^∗Corresponding author. Division of Pulmonary, Critical Care, and Sleep Medicine, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Bolwell Building 6174, Cleveland, OH 44106.Division of Pulmonary, Critical Care, and Sleep MedicineUniversity Hospitals Cleveland Medical Center11100 Euclid AvenueBolwell Building 6174ClevelandOH44106

Résumé

Based on the cystic fibrosis transmembrane conductance regulator (CFTR) genotype, approximately 90% of people with cystic fibrosis (CF) are candidates for highly effective modulator therapy (HEMT). Clinical trials conducted over the last 11 years have shown that these oral therapies substantially restore CFTR function, leading to improvements in lung function, nutritional status, and health-related quality of life. Here, we review safety and efficacy data from phase 3 clinical trials and observational studies which support the use of HEMT in most adults and children with CF. We also discuss opportunities for additional investigation in groups underrepresented or excluded from phase 3 clinical trials, and challenges in the evaluation of the safety and efficacy of HEMT at increasingly earlier stages of CFTR-mediated pathophysiology.

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Keywords : Cystic fibrosis, CFTR modulator, HEMT, Clinical trials