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Table 10Studies showing some relationship between rejection and method of MPA. Limited sampling strategies - Other

StudyPopulationTreatmentMajor Findings/ Comments
DeNofrio19 2000Organ transplanted: Heart (Cardiac)Dose: 1g BIDLower MPA AUC (as predicted by LSS of C0, C20min, C40min, C75min, and C120min) was associated with cardiac allograft rejection. Specifically, MPA AUC values were significantly lower in patients with Grade 2/3 than in patients with Grade 1 rejection (26.1 vs. 51.7 mg·h/L, p< 0.05)
Study design: Case seriesAge: Mean 53 +/- 10yConcomitant medications:
Length of followup: 310 +/- 278 daysCyclosporine
Kiberd57 2004Organ transplanted: Kidney (Renal)Dose: 2 g/day fixedDay 3 MPA AUC (based on LSS of C0, C1, C2, and C4) significantly predicted later rejection (p=0.007). The best cutoff point was an AUC concentration of 22 mg*h/L (sensitivity 82%, specificity 64%, negative predictive value 89% and positive predictive value 30%)
Study design: Case seriesAge:Mean 48 +/- 13yConcomitant medications:
Length of followup: 3 monthsPrednisone
Neoral
Kuriata-Kordek54 2002Organ transplanted: Kidney (Renal)Dose: 2.0 g/dayayC40min values were significantly lower in the patients with acute rejection compared with those without acute rejection (6.47 vs. 18.5 mg/L, p<0.05)
Study design: Case controlAge: Inclusion requirement group I: 38.12 +/- 9.5y, group II: 38.52 +/- 9.21yConcomitant medications:
Length of followup: 12 monthsCyclosporine
Prednisone
Le Meur10 2007Organ transplanted: KidneyFixed dose group: 1g BID; Concentration-controlled group: Days 1–7, 1g BID, then dose to target AUC of 40 mg*h/LIncidence of treatment failure, the primary study endpoint, was significantly lower in the concentration-controlled group (that used LSS of C20min, C1, and C3 developed by Bayesian methods, to target an AUC of 40 mg*h/L) compared with the fixed dose group (29.2% vs. 47.7%, p=0.03); percentage of acute rejection (12.3% vs. 30.7%, p=0.01) and biopsy-proven acute rejection (7.7% vs. 24.6%) were also lower in the concentration-controlled group.
Study design: RCTAge:Concomitant medications:
Length of followup: 12 monthsFixed dose group 49 +/- 13yCyclosporine
Concentration-controlled group: 50 +/- 14yMethylprednisolone
Basiliximab
Trimethoprim-sulfamethoxazole
Okamoto49 2005Organ transplanted: Kidney (Renal)Dose: 25 mg/kg initially, then adjusted afterwardsMPA AUC0–9 was significantly lower in patients with AR compared with those without (28.2 vs. 34.2 μg·h/mL, p=0.04085)
Study design: Non randomized controlled trialAge: Mean 38 +/- 14yConcomitant medications:
Length of followup: NRCyclosporine n=35
Tacrolimus n=32
Pawinski64 2006Organ transplanted: Kidney (Renal)Dose: 0.5 – 2 g/dayAUC (based on LSS of C0, C0.5, and C2) cut off for acute rejection of 27.5 mg·h/L had a diagnostic sensitivity of 81.2% and a diagnostic specificity of 93.4% (i.e., best predictor of acute rejection)
Study design: Case seriesAge: Range 17 – 62yConcomitant medications:
Length of followup: 3 monthsCyclosporine
Tacrolimus
Prednisone
Pawinski43 2006Organ transplanted: Kidney (Renal)Dose: 1 g BIDAUC (based on LSS of C0, C0.5, and C2) cut off of 24.1 mg·h/L had a diagnostic sensitivity of 77.8% and diagnostic specificity of 91.7% (best compared with predose and Cmax)
Study design: Case seriesAge: Mean 48yConcomitant medications:
Length of followup: 3 monthsRange 17 – 62yCyclosporine
Tacrolimus
Prednisone
Pillans59 2001Organ transplanted: Kidney (Renal)Dose: 2 g/dayMPA AUC (as predicted by a LSS of C0, C1, C3, and C6) was significantly lower in patients experiencing biopsy-proven rejection compared to those without rejection (27.6 vs. 35.1 mg·h/L, p=0.02). Four of 14 patients (29%) with an MPA AUC > 30 mg·h/L had a rejection episode but 8 of 13 patients (62%) with an MPA AUC <30 mg·h/L experienced a rejection
Study design: Case seriesAge: Range 21–65yConcomitant medications:
Length of followup: 1 monthCyclosporine
Prednisone
Weber63 2006Organ transplanted: Kidney (Renal)Dose: German study: 600 mg/m2 BSA up to 2 g/day suspension trial: 600 mg/m2 body surface area BID (up to 1000 mg BID), corresponding to 1 g MMF BID in adult renal transplant recipientsAUC (based on LSS of C0, C0.5, and C2) was able to discriminate patients with acute rejection from those with no rejection; AUC cut off of 36.8 mg.h/L had prognostic sensitivity of 66.7% and prognostic specificity of 61.9%
Study design: Case seriesAge: Range German study: 3.17–16.0y, Suspension trial: 1.0–16.0yConcomitant medications:
Length of followup: 6 months post-transplant suspension trial: 36 monthsCyclosporine CsA microemulsion: German study and suspension trial
Methylprednisolone German study
Prednisone suspension trial
Corticosteroids
Weber26 2002Organ transplanted: Kidney (Renal)Dose: 600 mg/m2 BID to a maximum of 2 g/dayAUC (based on LSS of C0, C75min, and C4) was able to discriminate between patients with and without acute rejection
Study design: Case seriesAge: Mean 11.8yConcomitant medications:
Length of followup: 6 monthsRange 3.2–16.0yCyclosporine A
Methylprednisolone
Weber17 2001Organ transplanted: Kidney (Renal)Dose: 600 mg/m2 BSA BID up to 2 g/day maxAUC (based on LSS of C0, C75min, and C4) was able to discriminate between patients with and without acute rejection
Study design: Case seriesAge: Range 2.2–17.8yConcomitant medications:
Length of followup: 6 monthsCyclosporine A
Methylprednisolone

Abbreviations: AR=Acute rejection, AUC=Area-under-the-concentration-time curve, BID=Twice Daily, BSA=Body Surface Area, C0=Predose Trough Serum or Plasma Concentration, Cmax=Maximum Serum or Plasma Concentration, CsA=Cyclosporin A, LSS=Limited Sampling Strategy, MMF=Mycophenolate Mofetil, MPA=Mycophenolic Acid, NR=Not Reported, RCT=Randomized Controlled Trial, y=Years

From: 3, Results

Cover of Utility of Monitoring Mycophenolic Acid in Solid Organ Transplant Patients
Utility of Monitoring Mycophenolic Acid in Solid Organ Transplant Patients.
Evidence Reports/Technology Assessments, No. 164.
Oremus M, Zeidler J, Ensom MHH, et al.

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