Azithromycin did not reduce extent of structural lung disease in infants with cystic fibrosis

Treatment with azithromycin from the time of diagnosis of cystic fibrosis in infancy did not reduce the extent of structural lung disease at age 36 months, but did reduce airway inflammation and morbidity, according to the COMBAT CF trial.

In addition, azithromycin treatment was safe and improved some clinical outcomes, researchers reported in The Lancet Respiratory Medicine.

“Until recently, there were no proven interventions in newborns with cystic fibrosis that address the basic pathological triggers for lung disease — airway dehydration and inflammation. There are now two options: hypertonic saline, which hydrates the airway and stops progression of structural damage, and azithromycin, which reduces inflammation,” Stephen M. Stick, PhD, from the department of respiratory and sleep medicine at Perth Children’s Hospital, the University of Western Australia and Wal-yan Respiratory Research Centre at Telethon Kids Institute, told Healio. “Azithromycin should be considered in combination with hypertonic saline for any young child who cannot access the new class of modulator therapy that is proving to be transformational for many older individuals with cystic fibrosis.”

Stick and colleagues conducted the randomized, double-blind, placebo-controlled, phase 3 COMBAT CF trial, which enrolled 130 patients from eight pediatric cystic fibrosis centers in Australia and New Zealand from June 2012 to July 2017. Infants were aged 3 to 6 months and had a diagnosis of cystic fibrosis. Infants were randomly assigned to receive oral azithromycin 10 mg/kg bodyweight (n = 68) three times a week or placebo (n = 62) until age 36 months.

The primary outcomes were the proportion of children with radiologically defined bronchiectasis and the percentage of total lung volume affected.

At age 36 months, 88% of infants assigned azithromycin and 94% assigned placebo had bronchiectasis (OR = 0.49; 95% CI, 0.12-2).

The researchers reported no difference between groups in total airways disease (median difference = –0.02%; 95% CI, –0.59 to 0.56).

Infants assigned azithromycin had fewer in-hospital days for pulmonary exacerbations (mean difference = –6.3; 95% CI, –10.5 to –2.1) and fewer courses of inhaled or oral antibiotics (incidence rate ratio = .88; 95% CI, 0.81-0.97).

Airway inflammation concentrations also were lower among infants assigned azithromycin, including interkeukin-8 (median difference = –1.2; 95% CI, –1.9 to –0.5) and neutrophil elastase activity (median difference = –0.6; 95% CI, –1.1 to –0.2) at 36 months in the preplanned exploratory analysis.

Researchers observed no azithromycin effect on BMI at 36 months (mean difference = 0.4; 95% CI, –0.1 to 0.9).

In addition, there was no evidence of pathogen emergence with azithromycin treatment and few adverse outcomes with no differences between those receiving the study drug or placebo, according to the researchers.

“[Cystic fibrosis transmembrane conductance regulator] modulator therapy is transforming the lives of people with cystic fibrosis,” Stick told Healio. “However, due to the cost of these therapies, very few young children outside of the U.S. can access them. ... Therefore, clinical trials in young children that compare efficacy of modulator therapies with azithromycin plus hypertonic saline are needed.”

For more information:

Stephen M. Stick, PhD, can be reached at stephen.stick@health.wa.gov.au.