Five-Year Outcome of an Early Everolimus-based Quadruple Immunosuppression in Lung Transplant Recipients: Follow-Up of the 4EVERLUNG Study.Kneidinger, N., et al.
Transplantation 2022; 03: 08.
This study aimed to report the five-year outcomes of the 4EVERLUNG study, which compared everolimus-based quadruple low calcineurin inhibitor (CNI) versus standard triple regimen in lung transplant recipients.
Patients were randomised to receive either the everolimus-based quadruple low CNI regimen or the standard triple regimen.
Data from 123 out of 130 lung transplant recipients randomised in the 4EVERLUNG study were analysed.
Renal function, biopsy-proven acute cellular rejection, chronic lung allograft dysfunction [CLAD], death and safety endpoints.
This paper reports the 5-year follow up of a previously published study in lung transplantation. The first publication showed that the addition of everolimus to standard immune suppression regimen allowed the minimisation of CNI exposure. Despite being underpowered, the original publication of the study demonstrated improved eGFR at 12 months, with no change in rejection rates or infectious complications. Over the total 5-year follow-up a substantial proportion (46%) had to switch away from the everolimus arm. There was a significantly increased risk of thromboembolic events in the everolimus arm of the study (24% versus 11%). At 5 years there was no significant difference in GFR between the 2 study arms (in both intention-to-treat and per protocol analysis). There was also no difference in graft survival. It seems that any short-term benefit in renal function is lost over time, whether switching back off everolimus or not. With such a susbtantial proportion changing immune suppression, crossing over and long term follow up with other potential medication changes, it does become difficult to separate effects.
ClinicalTrials.gov - NCT01404325