CF patients experience improved lung health with lumacaftor-ivacaftor but with caveats

October 11, 2019

Oct. 11, 2019--In adolescent and adult patients with cystic fibrosis taking lumacaftor-ivacaftor (ORKAMBI®), the combination drug appears to improve lung function and body weight and reduce the need for intravenous antibiotic treatment, according to a French study published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

However, nearly one in five patients could not tolerate treatment, most often due to adverse breathing events, during one year of follow up. The rate of discontinuation was considerably higher than previously reported in clinical trials, the authors wrote.

In "Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis," Pierre-Régis Burgel MD, PhD, and colleagues report on their study of 845 patients (292 adolescents, 553 adults) who were treated at 47 cystic fibrosis centers throughout France.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In 2015 the Food and Drug Administration and the European Medicines Agency approved lumacaftor-ivacaftor in treating patients who have inherited the same defective CFTR gene, known scientifically as the Phe508del mutation, from their parents.

"We felt it was important to obtain real-life post-marketing data in a large population of unselected patients with CF," said Dr. Burgel, a professor of medicine at Paris Descartes University and a physician at Cochin Hospital, Assistance Publique Hôpitaux de Paris. "Our findings provide a useful complement to randomized clinical trials in which participants were selected based on very strict criteria."

The study found that patients who took lumacaftor-ivacaftor continuously for 12 months experienced:The researchers found that 18.2 percent of participants in the study dropped out. According to the authors, this was "markedly" higher than "pivotal clinical trials," in which less than 5 percent of patients discontinued the combination therapy. Based on their findings, the authors believe the higher rates in the current study were likely the result of enrolling a higher proportion of patients with severe respiratory disease. However, discontinuation rates in patients with milder disease were also three times higher than in clinical trials, presumably because these patients had less stable disease, the authors said.

Nearly half the patients who discontinued treatment did so because of adverse respiratory events and more than a quarter discontinued treatment due to adverse non-respiratory events, most often digestive problems.

Other study findings:"For patients who are able to continue lumacaftor-ivacaftor, there is clinically meaningful improvement in respiratory disease and nutritional status," Dr. Burgel said. "However, our study found that the benefits and risks of new therapies cannot be extrapolated to patients who were excluded from clinical trials."
-end-
About the American Journal of Respiratory and Critical Care Medicine

The AJRCCM is a peer-reviewed journal published by the American Thoracic Society. The Journal takes pride in publishing the most innovative science and the highest quality reviews, practice guidelines and statements in pulmonary, critical care and sleep medicine. With an impact factor of 16.494, it is one of the highest ranked journals in pulmonology. Editor: Jadwiga Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute (Royal Brompton Campus), Imperial College London, UK.

About the American Thoracic Society

Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society's 15,000 members prevent and fight respiratory disease around the globe through research, education, patient care and advocacy. The ATS publishes three journals, the American Journal of Respiratory and Critical Care Medicine, the American Journal of Respiratory Cell and Molecular Biology and the Annals of the American Thoracic Society.

The ATS will hold its 2020 International Conference, May 15-20, in Philadelphia, Pennsylvania, where world-renowned experts will share the latest scientific research and clinical advances in pulmonary, critical care and sleep medicine.

American Thoracic Society

Related Cystic Fibrosis Articles from Brightsurf:

Treating cystic fibrosis with mRNA therapy or CRISPR
The potential for treating cystic fibrosis (CF) using mRNA therapies or CRISPR gene editing is possible regardless of the causative mutation.

Cystic fibrosis: why so many respiratory complications?
Cystic fibrosis, one of the most common genetic diseases in Switzerland, causes severe respiratory and digestive disorders.

A newly discovered disease may lead to better treatment of cystic fibrosis
Cystic fibrosis is the most frequent severe inherited disorder worldwide.

New treatment kills off infection that can be deadly to cystic fibrosis patients
The findings, which are published in the journal Scientific Reports, show that scientists from Aston University, Mycobacterial Research Group, combined doses of three antibiotics -- amoxicillin and imipenem-relebactam and found it was 100% effective in killing off the infection which is usually extremely difficult to treat in patients with cystic fibrosis.

Cystic fibrosis carriers are at increased risk for cystic fibrosis-related conditions
A University of Iowa study challenges the conventional wisdom that having just one mutated copy of the cystic fibrosis (CF) gene has no effects on a person's health.

Rare mutations drive cystic fibrosis in Caribbean
Cystic Fibrosis (CF) in the Caribbean is dominated by unusual gene mutations not often observed in previously studied CF populations, according to comprehensive genome sequencing led by physician-scientists at UC San Francisco and Centro de Neumología Pediátrica in San Juan.

Cystic fibrosis carriers at increased risk of digestive symptoms
Researchers have found that carriers of the most common genetic variant that causes cystic fibrosis experience some symptoms similar to those of people with cystic fibrosis.

In cystic fibrosis, lungs feed deadly bacteria
A steady supply of its favorite food helps a deadly bacterium thrive in the lungs of people with cystic fibrosis, according to a new study by Columbia researchers.

Cibio knocks out cystic fibrosis
The fight against cystic fibrosis continues, targeting in particular some of the mutations that cause it.

Hypertonic saline may help babies with cystic fibrosis breathe better
Babies with cystic fibrosis may breathe better by inhaling hypertonic saline, according to a randomized controlled trial conducted in Germany and published in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Read More: Cystic Fibrosis News and Cystic Fibrosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.