HDCN Abstract:  ASN Annual Meeting -- San Diego  

Schaier M, Scharpf D, Scholl C, et al.

Pharmacodynamic Drug Monitoring a New Tool for Individualised Immunosuppression in Patients with ANCA-Associated Systemic Vasculitis.

ASN Annual Meeting -- San Diego
J Am Soc Nephrol (Nov) 20:410A 2009

Background: Mycophenolic acid (MPA) exerts its immunosuppression by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH), depleting activated lymphocytes of guanine nucleotides and retarding their proliferation. MPA plays an increasing role in the maintenance therapy of ANCA- associated systemic vasculitis (AASV).

Objectives: The purpose of our study was to examine the correlation between clinical outcome and pharmacokinetic- pharmacodynamic relationships of MPA in patients with AASV.

Methods: We studied 27 Caucasian patients with stable AASV under maintenance therapy with MPA. MPA and IMPDH concentrations were measured by a validated high performance liquid chromatography method in 12 plasma samples collected at predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12h.

Results: Patients were followed for a mean (+/-SD) period of 14+/ -6 months. During observation period, no patient had a relapse, but three AASV patients showed a higher disease activity, with elevated BVAS. Patients with increased disease activity had significant higher levels of mean (+/- SD) IMPDH AEC (0-12) 91+/-20 nmol*h/mg protein/h, indicating inadequate IMPDH suppression. Stable patients had markedly lower IMPDH AEC (0-12) 57+/-23 nmol*h/mg protein/h (p=0.02). Maximum IMPDH concentration was significantly higher in patients with increased disease activity (p=0.02) in comparison to stable patients. Stable patients showed slightly higher MPA AUC (0-12) (70+/- 40 mg*h/L) in comparison to patients with increased BVAS (59+/-21 mg*h/L).The difference failed statistical significance (p=0.66). Furthermore, there was no statistical correlation between MPA AUC (0-12) and IMPDH AEC (0-12). The relative risk for increased disease activity is 6.6 time higher for patients with IMPDH AEC (0-12) > 60 nmol*h/mg protein/h and MPA AUC (0-12) < 68 mg*h/L.

Conclusion: Pharmacodynamic drug monitoring seems to be a new tool to detect inadequate immunosuppression in AASV patients.

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