Cystic fibrosis patients benefit from triple combination therapy: Study

Charite-Universitatsmedizin Berlin and the Max Delbruck Centre's findings were recently published in the European Respiratory Journal.

In many patients with cystic fibrosis, a hereditary condition, a three-drug combination therapy consisting of elexacaftor, tezacaftor, and ivacaftor is beneficial, increasing both lung function and quality of life, according to a study led by Charite two years ago.

Prof. Marcus Mall, the principal investigator in both trials, led a team that investigated for the first time whether this type of treatment is also beneficial in the long run, i.e. over a period of 12 months or longer. To investigate this, the researchers examined sputum or secretions from patients' respiratory tracts.

"In patients withcystic fibrosis, the mucus in the airways is very sticky because it doesn't contain enough water and the mucins, the molecules that form mucus, adhere too much due to their chemical properties. This results in thick, sticky mucus, which clogs the airways, making it harder for patients to breathe and leading to chronic bacterial infection and inflammation of the lungs," explained Mall, Director of the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and the Christiane Herzog Cystic Fibrosis Center at Charite.

In the study, the researchers show that a combination of elexacaftor, tezacaftor, and ivacaftor results in less viscous respiratory secretions and decreases inflammation and bacterial infection in the lungs of cystic fibrosis patients. "What's more, the effects lasted over the entire one-year study period. This is really important because previous medications caused a rebound in the bacterial load in the airways," explained Dr Simon Graber, who also works in the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine at Charite and was one of the co-leaders of the study. 79 adolescents and adults with cystic fibrosis and chronic lung disease participated in the trial.

"This is a major step forward in treating cystic fibrosis," said Mall. "At the same time, it would be premature to say that patients have been normalized, let alone cured. Chronic lung changes arising over many years of living with the disease cannot be reversed, unfortunately." This means patients with advanced lung disease will still need to rely on established treatments involving inhaling mucus-thinning medications, taking antibiotics, and physical therapy.

"We plan to forge ahead with our research on how to make treatments that address cystic fibrosis via the molecular defects that cause the disease -- like the triple medication combination studied here -- even more effective. This includes starting treatment in early childhood with the goal of preventing chronic lung changes wherever possible," Mall noted.

"Aside from that, this therapy is not available to about ten per cent of our patients right now due to their genetic conditions," Graber added. "That's why we are also hard at work on research involving new molecular treatments so we can treat all people with cystic fibrosis effectively."

The researchers are also working to advance their understanding of mucus defects in cystic fibrosis and develop new mucolytics, drugs that thin and loosen the mucus. This research could also benefit patients with common chronic inflammatory lung diseases such as asthma and COPD.

Cystic fibrosis is one of the most common fatal hereditary diseases worldwide. As many as 8,000 children, teens, and adults are living with the disease in Germany today. An imbalance in salt and water transport across mucosal surfaces of the body causes people with cystic fibrosis to produce thick, sticky secretions that harm organs such as the lungs, intestine and pancreas. This leads to progressive loss of lung function and shortness of breath, which still significantly lowers life expectancy despite advances in treatment. Some 150 to 200 children are born with this rare disease in Germany each year. (ANI)