THERAPEUTIC DRUG MONITORING OF MYCOPHENOLATE MOFETIL USING A LIMITED SAMPLING STRATEGY IN PATIENTS WITH LUPUS NEPHRITIS: AN AUSTRALIAN SINGLE CENTRE EXPERIENCE
Dr Aleksandra Djordjevic1, Dr Irene Ruderman1,2, Dr Mark K Tiong1,2
1Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia, 2Department of Medicine, The Royal Melbourne Hospital, Parkville, Australia
Aim: To examine the role of mycophenolic acid area-under the curve (MPA-AUC) in guiding mycophenolate mofetil (MMF) dosing, and assess associations with adverse effects and infection rates in patients with lupus nephritis (LN).
Background: The backbone of LN treatment is mycophenolic acid analogues (MPAA) such as MMF. Its active metabolite, MPA, displays large inter-patient variability but there is limited data as to whether therapeutic drug monitoring (TDM) improves the balance between achieving LN remission and managing toxicity.
Methods: A retrospective cohort study was conducted at The Royal Melbourne Hospital. Demographics, immunosuppression, biochemical data, adverse events and infective complications were collected over a 12-month period. Estimated MPA-AUC(0-12h) was calculated using trapezoid method. Pearsons correlation coefficient was utilised to explore correlations between estimated MPA-AUC(0-12h) and outcome variables.
Results: Nineteen estimated MPA-AUC(0-12h) measurements were collected across 16 patients with LN (n=13) and other glomerular diseases (n=3). Median MPA-AUC(0-12h) was 39.6 (IQR 29.8-44.5) mg∙hr/L with 4 (21.1%) patients being subtherapeutic and 2 (10.5%) supratherapeutic requiring dose adjustment to maintain a therapeutic range of 30-60 mg∙hr/L. Weight-based dosing was 34.5 (IQR 20.9-40) mg/kg and was significantly associated with estimated MPA-AUC(0-12h) (p=0.0364) whereas weight itself was not (p=0.3473). Higher estimated MPA-AUC(0-12h) did not correlate with number of adverse effects or infective complications.
Conclusion: Our data is representative of a real-world, single centre experience and demonstrates that TDM can be used to guide dosing of MMF in a glomerulonephritis setting. Weight-based MMF dosing was significantly associated with MPA-AUC(0-12h) and our results suggest that a fixed dosing strategy may not be appropriate for all patients with LN. Larger prospective studies are required to establish correlation between MPA-AUC, renal response and risk of toxicity.
Presentation Slides PDF – Click here
Biography:
Dr Aleksandra Djordjevic is a pre-Advanced Training Physician Trainee undertaking research with the Nephrology Department at The Royal Melbourne Hospital. She hopes to commence Nephrology Advanced Training in 2025.