Impact of tacrolimus vs cyclosporine on chronic lung allograft dysfunction incidence and allograft survival in the International Society of Heart and Lung Transplantation registry

Background: The ScanCLAD study reported a lower incidence of chronic lung allograft dysfunction (CLAD) with the use of once-daily tacrolimus vs twice-daily cyclosporine. Using the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant (TTX) Registry data, we evaluated the hypothesis that tacrolimus is superior to cyclosporine in real-world clinical practice.

Methods: This study is a retrospective cohort study of adult lung transplant recipients in the ISHLT registry from January 1, 2000, to June 30, 2018, with known CLAD status. The primary exposure variable was patients' maintenance calcineurin inhibitor (CNI) regimen captured at posttransplant discharge. The primary outcome variables were time to CLAD development (with death/retransplantation analyzed as a competing risk) and allograft survival (i.e., time to death/retransplant).

Results: Of the 57,403 adult lung transplant recipients in the registry, 22,222 had both CNI and CLAD data available. Of these, 19,698 (88.6%) received tacrolimus immediate release (IR), 2,477 (11.2%) received cyclosporine, and 47 (0.2%) received tacrolimus extended release (XR) for maintenance CNI. Receiving cyclosporine for maintenance immunosuppression (vs tacrolimus IR) was associated with an increased risk of developing CLAD (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08-1.23, p < 0.001) and with an increased overall risk for death/retransplant (HR 1.16, 95% CI 1.09-1.23, p < 0.001). Receiving tacrolimus XR vs tacrolimus IR was not associated with differences in long-term posttransplant outcomes, although these analyses were limited by a small sample size.

Conclusions: Patients receiving cyclosporine vs tacrolimus IR for maintenance calcineurin inhibition had an increased risk of CLAD and decreased overall allograft survival in the ISHLT TTX registry.