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).