Inhaled Cyclosporine May Increase Survival, Pulmonary Function After Lung Transplant

Inhaled liposomal cyclosporine may prevent bronchiolitis obliterans syndrome (BOS) progression following lung transplantation, according to a study published in ERJ Open Research.

“This drug may be a significant alternative that could improve the prognosis of [patients who undergo] lung transplant,” said Aldo T. Iacono, MD, University of Maryland School of Medicine, Baltimore, Maryland.

“While lung transplantation holds the promise of extending the lives of people with debilitating lung disease, chronic rejection, with its resulting decline in function, can wipe out that hope,” he added. “Patients are often as sick as they were before the transplant. Once that happens, the options often come down to another lung transplant, or death.”

Cyclosporine is traditionally given orally in pill form as part of the post-lung transplant standard-of-care regimen as 1 of several anti-rejection medications transplant recipients must take for the rest of their lives to prevent chronic organ rejection.

Despite these measures, the immune system often succeeds in attacking the transplanted organ, causing nearly half of lung transplant recipients to develop BOS within 5 years of getting their transplant.

For the current study, Dr. Iacono and colleagues followed 21 patients who underwent lung transplant and were in the early stages of BOS for 48 weeks. All of the patients were given conventional oral immunosuppressants, including tacrolimus, mycophenolate mofetil, and prednisone; 11 were randomised to also receive the inhaled cyclosporine twice daily for 24 weeks.

The researchers found that BOS progression-free survival was 82% for patients who took inhaled cyclosporine versus 50% for those who received standard care alone. BOS grade worsened in 18% of patients in the inhaled cyclosporine group versus 60% in the standard care alone group (P = .05). Lung function measures of forced expiratory volume and forced vital capacity stabilised in the treatment group, but worsened with the controls. Most importantly, the median survival for those who received the inhaled cyclosporine was 4.1 years compared with 2.9 years for those who did not receive the added therapy.

“We can get higher concentrations of the drug to the lungs through inhalation, compared [with] what we might get just by giving it by mouth,” said Bartley P. Griffith, MD, University of Maryland School of Medicine. “We are very pleased that we may be able to see this long-term idea realised in many more patients.”

“The results of this study stand as a tribute to the many years of research it sometimes takes to develop a bright idea into a patient benefit,” concluded Albert Reece, MD, University of Maryland School of Medicine. “The results are promising, and we look forward to the next phase -- a larger trial to confirm both these benefits and the lack of additional side effects from the inhaled drug.”

Reference: http://doi.org/10.1183/23120541.00167-2019

SOURCE: University of Maryland Medical Center
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