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The Impact of CFTR Modulators on Individuals with Cystic Fibrosis and Severe Lung Disease

September 9, 2021

Division of Pulmonary, Allergy and Critical Care Medicine physicians Michael Myerburg, MD, and Joseph Pilewski, MD, recently published an editorial in the American Journal of Respiratory and Critical Care Medicine on cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their impact on individuals with severe lung disease.  

CFTR Modulators to Treat Cystic Fibrosis

By defining the genetic, molecular, and cellular biology of cystic fibrosis (CF) mutations, physicians and researchers were able to identify compounds that partially restore CFTR function in patients with CF. 

The first highly effective CFTR modulator — ivacaftor (IVA) — was approved by the U.S. Food and Drug Administration in 2012 for patients with the G551D CFTR mutation. IVA has since been approved for several other mutations, giving 20% of CF patients access to an effective disease-modifying medication. In October 2019, The FDA approved elexacaftor-tezacaftor-IVA (ETI) which is a highly effective modulator for CF patients with at least one copy of F508del CFTR mutation. Given the frequency of the F508del CFTR mutation, now roughly 90% of CF patients benefit from highly effective CFTR modulators with dramatically improved lung function, nutritional status, and quality of life. 

While ETI has been thoroughly studied in individuals with mild to moderate CF lung disease, fewer studies have addressed the clinical impact for individuals with severe lung disease. Authors reviewed smaller studies demonstrating how ETI was well-tolerated and associated with dramatic improvements in lung function and weight. 

Lung Transplant for Cystic Fibrosis

Although CF providers have updated transplant referral guidelines to optimize the timing for lung transplant referral and listing as a treatment option for CF, they used data collected before CFTR modulators were used to reduce the rate of progression of CF lung disease. 

The use of CFTR modulators has significantly reduced the progression of CF lung disease, suggesting that survival with advanced CF lung disease will increase considerably. Because of this finding, authors consider the clinical implications of this new data on transplant referral and listing for the 90% of individuals with advance CF lung disease on CFTR modulators. 

They suggest that early referral for lung transplant remains necessary for patients with CF and severe lung disease to provide patients and their families information regarding transplant as a treatment option, identify and remediate barriers to transplant, and establish a safety net if patients develop respiratory failure. 

As physicians and researchers collect more data to inform best practices for lung transplant referral and listing, the authors recommend that health care providers continue to recognize the impact that CFTR modulators have on both quality of life and survival for their CF patients. 

Read the editorial and see full list of references here


Myerburg M, Pilewski JM. CFTR Modulators to the Rescue of Individuals with Cystic Fibrosis and Advanced Lung Disease. Am J Respir Crit Care Med. 2021 Jul 1;204(1):7-9. doi: 10.1164/rccm.202103-0674ED.