Long-term Antibiotics Ease Symptoms of Genetic Lung Disorder

Ingrid Hein

October 04, 2019

MADRID — For patients with primary ciliary dyskinesia, continuous maintenance therapy with azithromycin reduces exacerbations by 50%, according to the results from the BESTCILIA trial.

"This is a heterogeneous disease with a lot of exacerbations and low lung function, and this group of patients often needs antibiotic treatment," said Helene Kobbernagel, MD, from the Copenhagen University Hospital.

"We have shown that the benefits of maintenance therapy with azithromycin for these patients is quite good," she reported here at the European Respiratory Society 2019 International Congress.

Primary ciliary dyskinesia is an autosomal recessive genetic disorder that presents in about one in 16,000 births in the United States. "But we believe it is underdiagnosed because it resembles other diseases," Kobbernagel told Medscape Medical News.

Because the disease affects mobility of the cilia in the lungs, patients are susceptible to frequent respiratory infections.

Azithromycin is a macrolide antibiotic that has an anti-inflammatory effect, mild adverse effects, and is effective for a number of infections that occur in people with the disease. "These are important considerations if you are asking children and adults to take a drug for an extended period," said Kobbernagel.

In addition, recent evidence has shown that azithromycin reduces acute exacerbations for COPD, as reported by Medscape Medical News, and might be helpful in idiopathic pulmonary fibrosis.

Effective for Symptomatic Patients

The 90 European patients in the double-blind randomized BESTCILIA trial were 7 to 50 years of age and had a confirmed diagnosis of primary ciliary dyskinesia. Forty-nine received azithromycin 250 or 500 mg, depending on whether body weight was below or above 40 kg, three times weekly for 6 months, and 41 received placebo. Patients were assessed every 2 months.

After 6 months, there were significantly fewer exacerbations in the azithromycin group than in the placebo group (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.27 - 0.80; P = .006) and significantly fewer pathogenic bacterial species in the sputum (rate ratio, 0.39; 95% CI, 0.24 - 0.64; P = .0002).

In addition, more patients in the azithromycin group than in the placebo group remained free of exacerbations (60% vs 40%).

"Exacerbations were reduced to half, and many more patients had zero exacerbations in the study group than in the placebo," said Kobbernagel. "The treatment also markedly prolonged time to exacerbation."

Lung function, hearing level, and respiratory, sinus, ear, and hearing symptoms were not significantly different in the two groups. "I was surprised we did not see any efficacy on these," she said. "I would have thought that over 6 months, that quality of life would improve."

This therapy could be especially effective for certain patients. However, "not every patient should take maintenance therapy," she said. "Some primary ciliary dyskinesia patients have normal lung function and not that many symptoms."

And "we don't know yet if it will show signs of efficacy if you take it for more than 6 months," Kobbernagel added. "We need to study whether it still works if you take it for 2 years."

This is a proof-of-concept study. We need more studies that look at long-term treatment with antibiotics.

This treatment might be effective if taken for 6 months during the winter, when infections are more prevalent, said Tobias Welte, MD, from the Hannover University School of Medicine in Germany. "Then take a break to allow the microbiome to normalize itself."

Azithromycin has a unique profile and "a kind of antiviral effect" that researchers do not entirely understand, he explained. It also "influences the binding of the virus to the lung epithelium."

"This is a proof-of-concept study. We need more studies that look at long-term treatment with antibiotics," Welte told Medscape Medical News.

Still, he said, "these patients are at risk for worsening of lung function and they have a bad prognosis; this is a clear step forward."

Concerns About Resistance

Antibiotic maintenance therapy only works if it is continual; otherwise, bacteria can develop again, said Kobbernagel. Discontinuations could lead to bacteria becoming resistant to the drug.

"We didn't see any more signs of resistance with azithromycin than with placebo, but we only had about 40 samples," she acknowledged.

When patients with primary ciliary dyskinesia follow this treatment, their sputum samples need to be looked at consistently, she cautioned, adding, that she was "surprised that some of the centers that participated in this study weren't routinely checking for resistance."

"To give this treatment, you have to make use of your microbiology department," Kobbernagel said.

Kobbernagel has disclosed no relevant financial relationships. Welte reports receiving honoraria for lectures from AstraZeneca, Boehringer, GSK, and Novartis.

European Respiratory Society (ERS) 2019 International Congress: Abstract RCT5102. Presented October 2, 2019.

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