Feasibility of, and critical paths for mycophenolate mofetil Bayesian dose adjustment: Pharmacological re-appraisal of a concentration-controlled versus fixed-dose trial in renal transplant recipients

Graft Loss and Mortality Outcomes from kidney transplantation remain suboptimal. 1-3 Effective immunosuppressive drugs, along with attention to cardiovascular disease 4 and prophylaxis against infection, 5 have significantly reduced rates of acute rejection (15.4%), graft loss (3.6%), and death (2.8%) in the first posttransplant year for standard risk recipients. 6 However, time to allograft failure remains substantially shorter than typical recipient life expectancy following transplantation, due largely to chronic antibody-mediated rejection. 7-10 Approximately 20% of kidney allograft

show abstract

“…Thus, if larger dose increments had been allowed, the benefit of TCI may have been even greater. 107…”

Section: Resultsmentioning

confidence: 99%

Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The results of the APOMYGRE study confirmed the benefit of therapeutic drug monitoring (TDM) in the management of kidney transplantees and the advantage of dose adaptation to maintain MPA AUC(0,12 h) above a target value of 45 mg l –1 h to prevent graft rejection . For patients with autoimmune diseases, optimization of immunosuppressive therapy is still a major concern for clinicians and pertinently raises the question of MMF‐TDM in non‐transplant patients.…”

Section: Introductionmentioning

confidence: 77%

Pre‐dose plasma concentration monitoring of mycophenolate mofetil in patients with autoimmune diseases

Streicher

Djabarouti

Xuereb

et al. 2014

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aim To date, neither the benefit of mycophenolic acid (MPA) therapeutic drug monitoring (TDM), the prodrug of mycophenolate mofetil (MMF), nor the optimal monitoring technique have been established in autoimmune diseases. This study was undertaken to confirm, in a cohort of new patients, the plasma MPA thresholds previously published in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods MPA areas under the concentration–time curves between 0 and 12 h, 12 h trough concentrations and pre‐dose concentrations (C0) were determined for 23 patients with SLE and 21 with systemic vasculitis. The relationship between patients' pharmacokinetic (PK) variables and their clinical outcomes during follow‐up were analyzed. Results In both autoimmune diseases, at PK assessment, median MPA C0 for patients with uncontrolled disease was significantly lower than that of patients with stable disease or in remission, 1.6 mg l–1 (IQR 0.9–2.1 mg l–1) vs. 2.95 mg l–1 (IQR 1.38–3.73 mg l–1) for SLE (P = 0.048) and 1.55 mg l–1 (IQR 0.98–2.18 mg l–1) vs. 3 mg l–1 (IQR 2.2–4.4 mg l–1) for vasculitis (P = 0.016). According to our receiver operating characteristics curve analysis, a C0 threshold of 2.5–3 mg l–1 was best able to discriminate a flare (SLE: 88% sensitivity, 80% specificity; vasculitis: 100% sensitivity, 90% specificity). Patients with C0 ≥ 2.5–3 mg l–1 at inclusion had better clinical outcomes during the 12 months following PK assessment. Conclusion Provided that the benefit of TDM in patients with autoimmune diseases could be confirmed by randomized, controlled trials, it might be based on the C0 measured approximately 12 h post‐dose.

show abstract

“…Clinical efficacy can only be tested if the procedures are efficient in separating the study arms and providing the clinical intervention intended. 181 The APOMYGRE trial also showed that MMF dose adjustment guided by AUC-MPA, beyond being clinically efficient, was quite affordable if not actually cost-saving: approximately €3757 for each treatment failure avoided, in 2010 euros. 182 The first pediatric PK/PD study in KTR was published in 2002 by Weber et al, 183 who found in 54 children (aged 2-17 years) that both AUC and predose concentration were associated with the risk of acute rejection.…”

Section: Mpa Exposure Efficacy and Toxicity-kidney Transplantationmentioning

confidence: 99%

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Bergan¹,

Brunet²,

Hesselink³

et al. 2021

Therapeutic Drug Monitoring

116

237

View full text Add to dashboard Cite

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and

show abstract

Feasibility of, and critical paths for mycophenolate mofetil Bayesian dose adjustment: Pharmacological re-appraisal of a concentration-controlled versus fixed-dose trial in renal transplant recipients

Cited by 13 publications

References 16 publications

Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention

Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention

Pre‐dose plasma concentration monitoring of mycophenolate mofetil in patients with autoimmune diseases

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Contact Info

Product

Resources

About