The most effective prevention method for complications post lung transplant

When receiving a lung transplant, one of the most important complications to look out for is chronic lung allograft dysfunction, known as CLAD.

Preventing this complication for those who receive a lung transplant is of the highest priority, as there are no universally effective treatments for CLAD once it is established.

The most common of the immunosuppressing medications given to lung transplant recipients are calcineurin inhibitors.

Only two calcineurin inhibitors exist, cyclosporine and tacrolimus, and the available formulations are once-daily slow-release tacrolimus, twice-daily immediate-release tacrolimus and twice-daily cyclosporine.

While the medications have the same end goal, preventing rejection, whether they are equally effective is unknown.

Chronic lung allograft dysfunction is a label for a wide range of clinical manifestations that all lead to the transplanted lung losing its normal function.

There can be some variation in how CLAD presents, as some patients have an obstructive ventilatory defect, some have a restrictive defect, and some have a mix of the two.

Regardless of the type, however, once chronic lung allograft dysfunction develops, lung function does not improve.

In the absence of effective treatments, strategies to prevent CLAD are crucial.

Using the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry data, a research team led by Michael Combs, M.D., M.S., an assistant professor of pulmonary diseases and internal medicine at Michigan Medicine, conducted the first study to show a survival benefit between using the treatments tacrolimus versus cyclosporine after lung transplantation.

Out of the 22,222 individuals with data for chronic lung allograft dysfunction treatment, 88.6% received tacrolimus immediate release.

The participants taking immediate release tacrolimus had a much lower rate of experiencing chronic lung allograft dysfunction than their counterparts that took twice-daily cyclosporine.

Combs wanted to highlight the positive finding for the twice-daily immediate release tacrolimus in this study. 

“The Scan-CLAD study published earlier in the year found that tacrolimus once-daily extended-release had the best outcomes with regards to preventing the development of chronic lung allograft dysfunction, but the vast-majority of patients in actual practice are on twice-daily tacrolimus,” said Combs.

“This present study should reassure transplant patients and providers twice-daily tacrolimus—and not only once-daily tacrolimus—is the superior treatment to cyclosporine.” 

“Importantly,” Combs added, “in our study we found that twice-daily tacrolimus not only resulted in lower rates of CLAD relative to cyclosporine, but it was also associated with improved overall survival after lung transplantation. This is an important, patient-centered finding which has not been previously demonstrated.”

“Given the theoretical benefits of once-daily medication regiments, future research will need to investigate if either tacrolimus XR and tacrolimus IR are superior to each other. However, until then, we can rest assured knowing that tacrolimus—regardless of its formulation—is the best option for our lung transplant patients,” he stated.

Additional authors: Krysta Walter, PharmD and Haley Hixson, PharmD, from the department of pharmacy, University of Michigan, Ann Arbor. Elizabeth A. Belloli, M.D., Kevin M. Chan, M.D., and Dennis M. Lyu, M.D., from the department of medicine, division of pulmonary & critical care, University of Michigan, Ann Arbor. Mattew S. Major, Ph.D., from the department of pathology, University of Michigan, Ann Arbor. Andrew C. Chang, M.D., from the department of surgery, University of Michigan, Ann Arbor.

Paper cited: “Impact of tacrolimus vs cyclosporine on chronic lung allograft dysfunction incidence and allograft survival in the International Society of Heart and Lung Transplantation registry,” The Journal of Heart and Lung Transplantation.  DOI: 10.1016/j.healun.2024.10.013

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