Figure S2 . Meta-analysis of studies reporting mean±SD MPA
AUC0-12 at steady-state in renal transplant recipients
treated with IR MMF and co-treated with CsA or macrolactams (tacrolimus
or sirolimus) and genotyped for SLCO1B3 c.334T>GSNP, classified as TT/TG vs. GG patients. The effect measure is ratio of
means (ROM).
In CsA co-treated subjects, one study indicated no relevant difference
between TT/TG and GG patients, while two suggested somewhat higher AUC
in TT/TG patients: the pooled estimate was ROM=1.173 (0.941-1.461)
(Figure S2) indicating a tendency of slightly higher exposure in TT/TG
patients (total N=110) than in GG patients (total N=208).
In macrolactam co-treated patients, two studies suggested somewhat
higher AUC in TT/TG vs. GG patients, and one suggested somewhat lower
values: the pooled estimate was ROM=1.121 (0.594-2.114) (Figure S2) not
indicating any relevant difference in exposure between TT/TG (total
N=131) and GG patients (total N=192).
The overall estimate (ROM=1.136, 0.949-1.361) (Figure S2) indicated a
possibility of slightly higher exposure in TT/TG (total N=241) than in
GG patients (total N=400), but uncertainty (due to heterogeneity best
illustrated by the wide prediction intervals extending from 27% lower
to 77% higher AUC) about the size of the effect (difference) was
considerable.
We identified 3 studies reporting total exposure to MPA over dosing
interval at steady-state [AUC0-12 (mg ×h/L) calculated
based on dose-adjusted MPA concentrations] in renal transplant
patients classified in respect to the UGT1A9 c.98T>CSNP as variant carriers (TC) vs. wild type subjects (TT): one French
(Picard 2010 [1]) and one Dutch (van Schaik 2009 [5]), each
reporting values in patients on IR MMF co-treated with either CsA or
macrolactams; one Belgian (Kuypers 2005 [6]) in which MMF was
combined with tacrolimus. Two studies (Picard 2010, Kuypers 2005 [1,
6]] reported crude, unadjusted mean±SD AUC0-12quantified at different post-transplantation times (Figure S3).