Tacrolimus or cyclosporine for CLAD: The better of 2 immunosuppressants

Tacrolimus given once daily significantly reduced the 3-year incidence of chronic lung allograft dysfunction (CLAD) in lung transplant patients compared with standard immunosuppressant in the open label, multicentre, ScanCLAD trial presented at ERS 2023.

CLAD incidence was less frequent with tacrolimus than cyclosporine (13 percent vs 39 percent; p<0.0001) at 36 months after double lung transplantation.

Overall survival (OS) did not differ between groups at 3 years, but allograft survival was significantly better with tacrolimus (HR, 0.49; p=0.021) in the per protocol CLAD population, reported Dr Göran Dellgren from the University of Gothenburg, Sweden.

He said the finding was unexpected. “We did not think we would have such results. We thought it was good enough with cyclosporine, but we were wrong. Tacrolimus should be the first choice of calcineurin inhibitor following lung transplantation.”

Limited treatment options

CLAD is the main limiting factor for long-term survival after lung transplantation, with patients typically presenting with dyspnoea on exertion and nonproductive cough. Despite being a major cause of post-lung transplant mortality, treatment options remain limited.

Tacrolimus and cyclosporine are calcineurin inhibitors used for immunosuppression in lung transplantation. However, there are limited clinical trials published on the choice of calcineurin inhibitors after transplantation.

In the ScanCLAD trial, patients were randomly assigned to cyclosporine once daily (n=125) or tacrolimus twice daily (n=124). Average patient age was 55.2. Forty-five percent were women. Majority of them were White and former smokers. About 30 percent  had chronic obstructive pulmonary disease. [Lancet Respir Med 2023; S2213-2600(23)00293-X.]

Patients received surveillance bronchoscopies 1, 3, and 12 months after the procedure and were followed up until 36 months.

Adverse events (AEs) were slightly less common with tacrolimus (1,459) vs cyclosporine (1,516). Infection was the most frequently observed AE, followed by anaemia, and acute rejection in both treatment groups. Re-transplantation was higher in the cyclosporine group, which translated into worse allograft survival in the cyclosporine [per protocol] CLAD population, reported Dellgren.

New face to treatment

In an accompanying editorial, Dr Michael Combs from the University of Michigan in Ann Arbor, Michigan, US said the once daily dosing of tacrolimus used in ScanCLAD introduced a new face to the post-transplant treatment. [Lancet Respir Med 2023;S2213-2600(23)00307-

“Comparisons of tacrolimus once vs twice daily dosing after lung transplantation have been limited to pharmacokinetic and safety studies, which showed that both formulations can be maintained in the target range, with similar rates of adverse events,” he shared. “In the largest study comparing tacrolimus once vs twice daily in lung transplant recipients, patients were less likely to take their medication irregularly or miss doses with the once daily formulation.”

He noted that the once-daily dosing has been shown effective for other solid organ transplants that the International Society for Heart and Lung Transplantation has recommended the once per day dose in its consensus guideline. “This raises the question of whether real-world use of once-daily tacrolimus might result in more efficacious immunosuppression and lower rates of CLAD and rejection,” he added.