Therapeutic drug monitoring of mycophenolate mofetil for the treatment of severely active lupus nephritis

Kittanamongkolchai, Wonngarm; Rukrung, Chutima; Supasiri, Thanan; Lertjirachai, I; Somparn, Poorichaya; Chariyavilaskul, Pajaree; Avihingsanon, Yingyos

doi:10.1177/0961203313486949

Cited by 31 publications

(23 citation statements)

References 15 publications

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“…It is worth mentioning that the main limitation of the majority of the studies, 10,11,[27][28][29][30][31] with exception of the study conducted by Zahr et al, 9 is the small sample size that ranges from 5 to 34 patients. Moreover, although free MPA fraction is pharmacologically active, none of the studies conducted so far has determined the free fraction of MPA.…”

Section: Correlation Between Mpa Pharmacokinetics and Renal Response mentioning

confidence: 96%

“…These results were further explored by the same study group. Kittanamongkolchai et al 28 determined that MPA C 1 may constitute a practical tool for monitoring the patients' exposure on MPA because 78% of patients achieved the target MPA AUC 0-12 h level of 45 mg$h$L 21 when the MMF dosage was so adjusted as to reach MPA C 1 concentration of more than 13 mg/L. Even when MPA AUC 0-12 h target level was not achieved, it was close to the target only if MPA C 1 target has been reached.…”

Section: Correlation Between Mpa Pharmacokinetics and Renal Response mentioning

confidence: 99%

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Therapeutic Drug Monitoring of Mycophenolic Acid in Lupus Nephritis

Łuszczyńska

Pawiński

2015

Therapeutic Drug Monitoring

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In recent years, mycophenolate mofetil (MMF)-based immunosuppressive regimen was recommended in induction and in maintenance therapy in lupus nephritis (LN), one of the most severe and common manifestations of systemic lupus erythematosus. However, no recommendations were made so far regarding monitoring of mycophenolic acid (MPA) plasma concentrations. Therapeutic drug monitoring (TDM) constitutes a practical tool to ensure optimal posology. In renal transplantation, it was proved that acute allograft rejection incidences decreased when the recommended MPA target exposure has been maintained (30-60 mg·h·L). The results obtained in the field of transplant medicine indicate the potential benefit of carrying out TDM in LN. To date, the correlation of MPA exposure and clinical outcomes in the population of LN patients was the objective of just a few studies. The aim of this review was therefore to present TDM studies in LN patients on MMF therapy and to compare their results. Based on the conclusions drawn from TDM studies in LN, it can be suggested that the area under the concentration-time curve threshold values of 30-45 mg·h·L can potentially be associated with favorable treatment outcome. Moreover, the majority of the analyzed studies indicate relatively good correlation between trough concentration and the area under the concentration-time curve in patients treated with MMF that constitutes an important implication for TDM approach in routine setting. The threshold of 3 mg/L can potentially be recommended as a target trough value.

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Section: Correlation Between Mpa Pharmacokinetics and Renal Response mentioning

confidence: 96%

Section: Correlation Between Mpa Pharmacokinetics and Renal Response mentioning

confidence: 99%

Therapeutic Drug Monitoring of Mycophenolic Acid in Lupus Nephritis

Łuszczyńska

Pawiński

2015

Therapeutic Drug Monitoring

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“…The results also highlighted the importance of socioeconomic issues in health care access and delivery in Asian countries. Also, studies in Thai patients have shown that there was a marked interindividual difference in MPA metabolism and that drug exposure was related to therapeutic response [73,74]. In this regard, there are ongoing studies on the pharmacokinetics and pharmacogenomics of MPA in different Asian populations.…”

Section: Discussionmentioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

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Background: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Summary: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Key Messages: Treatment responses and clinical outcomes in Asian patients with LN compare favorably with patients from other parts of the world. The prevention and treatment of infective complications remain significant challenges in managing LN in Asia. Facts from East and West: (1) The prevalence of SLE is lower among Caucasians than other ethnicities. A higher prevalence is observed among Asians and African Americans, while the highest prevalence is found in Caribbean people. The prevalence of LN in Asian SLE patients is much higher than in Caucasians as well. However, the 10-year renal outcome and renal survival rate appear to be better in Asians. (2) Polymorphisms of genes involved in the immune response, such as Fcγ receptor, integrin alpha M, TNF superfamily 4, myotubularin-related protein 3 and many others, might be partly responsible for the differences in prevalence between the different ethnic groups. European ancestry was shown to be associated with a decrease in the risk of LN even after adjustment for genes most associated with renal disease. (3) Access...

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“…[150][151][152] Treatment to a 1 h post-dose target level of mycophenolic acid >13 mg/l resulted in a response rate of 89% in 19 patients with class III or IV lupus nephritis. 153 Further investigation is required to establish whether measurement of blood drug levels at a single time point can replace area-underthe-curve analysis, and to establish what drug level is necessary to ensure efficacy during different phases of treatment. Notwithstanding these uncertainties, research to date suggests that drug level monitoring should have a role in improving the outcomes of patients treated with mycophenolic acid based medications.…”

Section: Induction Treatmentmentioning

confidence: 99%

Treatment of severe lupus nephritis: the new horizon

Chan

2014

Nat Rev Nephrol

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Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

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Therapeutic drug monitoring of mycophenolate mofetil for the treatment of severely active lupus nephritis

Abstract: MPA-C1 may be a practical monitoring of MPA levels in patients with LN. It is convenient to monitor and may facilitate an optimum estimate of MPA exposure.

Cited by 31 publications

References 15 publications

Therapeutic Drug Monitoring of Mycophenolic Acid in Lupus Nephritis

Therapeutic Drug Monitoring of Mycophenolic Acid in Lupus Nephritis

Lupus Nephritis in Asia: Clinical Features and Management

Treatment of severe lupus nephritis: the new horizon

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