Impact of Tacrolimus vs. Cyclosporine on CLAD Incidence and Allograft Survival in the ISHLT Registry.

Abstract

PURPOSE The ScanCLAD study reported a lower incidence of CLAD with the use of once-daily tacrolimus vs. twice-daily cyclosporine. Using the 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 through June 30, 2018 with known CLAD status. The primary exposure variable was patients' maintenance calcineurin inhibitor (CNI) regimen captured at post-transplant 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 (HR 1.16, 95% 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 post-transplant 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.