Mycophenolate Mofetil trough levels and Chronic Lung Allograft Dysfunction in lung transplant recipients

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C.L.A. Pladet, K.M. Vermeulen, W. van der Bij, G.N. Nossent, M.E. Erasmus, E.A.M. Verschuuren

Chair(s): Drs. F.E. van Reekum & dr. M.C. Warlé

Wednesday 8 march 2017

17:54 - 18:06h at Johan de Meesterzaal

Categories: Parallel - Klinisch

Parallel session: Parallelsessie VII - Klinisch 2 - Nazorg na orgaantransplantatie

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Mycophenolate Mofetil (MMF) is standard immunosuppression in lung transplant (LTx) recipients. Research into MMF pharmacokinetics has revealed great variability of inter- and intrapatient MPA bio-availability. Advised target range in lung transplantation is 2,5-4.5 mg/L. However, daily dose is often reduced based on side effects irrespective of trough levels. We studied whether low MMF trough levels is related to the development of chronic lung allograft dysfunction (CLAD). A better understanding of MMF dose, trough level and its relation to CLAD may improve treatment strategies for LTx.

MMF mean trough level and development of CLAD was retrospectively studied in 142 LTx patients transplanted between 2009 and august 2014. Immunosuppression consisted of tacrolimus, MMF and prednisolone. Standard daily dose of MMF is 2x1000mg. MMF trough levels were routinely measured but MMF doses were not adjusted to these levels. Other variables were mean trough Tacrolimus level, BMI, sex, indication, age, and CMV status. Mortality, malignancies and infectious complications were also studied.

MMF dose was reduced in 117 of 142 pts. Mean trough level of MMF was 1,78 mg/L (SD 0,97) and 1,63 (SD 0,80) in the patients without and with CLAD respectively (p=NS). 119 out of 142 pts had a mean trough level below the advised range of 2.5-4.0 mg/L. Mean MMF trough level was lower in Cystic Fibrosis (CF) patients (1,35 vs 1,84 mg/L, P<0,025) but this did not result in a higher incidence of CLAD.  A high Body Mass Index (BMI) at the moment of transplantation (p=0.001) and Female gender (p=0,047) were independently associated with CLAD.

We conclude that there is no relation between mean MMF trough level and CLAD and that our current strategy of reducing MMF dosage based on side effects seems to be safe in respect to CLAD. The currently advised range of MMF might be too high in the context of our triple immunosuppression.