Everolimus as a treatment of Chronic Lung Alograft Rejection (CLAD) in lung transplantation

Abstract

Everolimus is an inhibitor of mTOR (mammalian target of rapamycin). Our study describes and assesses the efficacy of everolimus in the control of Chronic Lung Allograft Dysfunction (CLAD).

Methods: Retrospective study at two lung Transplantation Spanish centers. We evaluated 57 adult lung transplantation recipients (LTR) who received everolimus as a treatment for CLAD. Variables analyzed: FEV1, FVC, Restrictive Allograft Syndrome (RAS) grade, grade of Bronchiolitis Obliterans Syndrome (BOS), creatinine, cholesterol and triglycerides. We calculated the fall slopes of FEV1 and FVC 12 months before and 48 months after starting everolimus. The primary endpoint of the study was to assess the efficacy of this therapy by improving the fall slope of FEV1 after the treatment.

Results: 57 LTR were included in the study. Patients were male in 66.7% with a mean age of 54 years. Everolimus improved the fall slope of FEV1 from 3 months before treatment (-117.24ml/month) to 3 months after treatment (-42.81 ml/month) p = 0.001. It also improved the fall slope of FEV1 from 6 months before treatment (-81.37ml/month) to 6 months after treatment (-18.12 ml/month) p = 0.000. There was an improvement in the creatinine level when comparing 3 months before and 3 months after everolimus start (0.18g/dl) p=0.035. The blood cholesterol and triglycerides levels increased progressively during the first year after everolimus began, 26.29 mg/dl (p=0.004) and 44.52mg/dl (p = 0.003) respectively, both had a maximum increase during the first month.

Conclusion: Everolimus is effective as treatment for CLAD since it improves the loss of FEV1. We also observed an improvement of other laboratory parameters like creatinine.