Association between mycophenolic acid 12-h trough levels and clinical endpoints in patients with autoimmune disease on mycophenolate mofetil.
BACKGROUND
Triggered by heightened interest in mycophenolate mofetil (MMF) for the treatment of autoimmune diseases (AID) and encouraged by the results from a previous study, we hypothesized that therapeutic drug monitoring of mycophenolic acid (MPA) based on troughs may be useful for effective MMF dosing in patients with AID.


METHODS
A two-step approach was pursued. First, we confirmed in 38 AID patients (26 with antineutrophil cytoplasmic antibody-associated vasculitis; 12 with systemic lupus erythematosus) a significant correlation (r = 0.545, P < 0.001) between MPA C(12 h) and MPA exposure (AUC). Second, we performed an analysis of 294 MPA 12-h trough levels serially collected from 39 patients (same indications) receiving MMF for remission maintenance therapy to elucidate possible associations with disease activity and MMF toxicity.


RESULTS
Higher MPA trough levels were associated with better protection from recurrence of active disease. While at levels <3 mg/L 29% of collected samples (43/147) were from patients with active disease, this was only the case in 2% of samples (3/147) with an MPA concentration of >or=3 mg/L. Remission persisted in all patients with MPA troughs >or=3.5 mg/L. Upon combined analysis of efficacy and safety data, most favourable results were obtained with MPA troughs between 3.5 and 4.5 mg/L. There was no discernable relationship between MMF dose and clinical endpoints.


CONCLUSIONS
The target range proposed by this explorative study may serve as an initial guidance for MPA monitoring in the context of further prospective controlled trials in patients with AID.
Neumann
Irmgard
I
6th Department of Internal Medicine, Nephrology and Dialysis, Wilhelminenspital, Vienna, Austria. irmgard.neumann@wienkav.at
Fuhrmann
Heinz
H
Fang
I-Fei
IF
Jaeger
Adelheid
A
Bayer
Peter
P
Kovarik
Josef
J
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000097:blood* / Q000188:drug therapy*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014657:Vasculitis / Q000097:blood / Q000188:drug therapy
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid