Dataset Information

Real-World Experience of Safety of Mycophenolate Mofetil in 119 Japanese Patients with Systemic Lupus Erythematosus: A Retrospective Single-Center Study.

ABSTRACT:

Objectives

Mycophenolate mofetil (MMF) is the standard treatment for lupus nephritis. In Japan, it was approved for lupus nephritis in 2015. We investigated its real-world safety and effectiveness in Japanese patients with systemic lupus erythematosus (SLE).

Methods

We analyzed the continuation rate, adverse events, and reasons for discontinuation of MMF in Japanese patients with SLE in a retrospective single-center study. We included 119 patients who received MMF from 31 July 2015 to 31 May 2019. To compare demographic and clinical characteristics between groups, the Mann-Whitney U-test was used for nonnormally distributed variables. Categorical variables were compared using Fisher's exact test. Kaplan-Meier curves were plotted for the discontinuation rate of MMF.

Results

Patients consisted of 18 males and 101 females. Thirty-five patients discontinued MMF. The cumulative discontinuation rate was 42.4%. Twenty-nine patients discontinued MMF due to adverse events, and six patients discontinued MMF due to remission of SLE or desire for childbearing. At the time of the last observation, the lupus low disease activity state achievement rate was significantly lower in patients who experienced adverse events than those who did not (64% vs. 35%, P = 0.009). We examined the concentration of mycophenolate acid (trough level) in stored frozen serum in 11 patients. Two patients had irreversible complications due to viral meningitis; their trough mycophenolate acid concentrations were 8.3 and 6.3??g/mL, respectively.

Conclusions

Although MMF may be effective in Japanese patients with SLE, physicians should pay attention to infections in patients with high mycophenolate acid concentrations.

SUBMITTER: Abe Y

PROVIDER: S-EPMC7850850 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Real-World Experience of Safety of Mycophenolate Mofetil in 119 Japanese Patients with Systemic Lupus Erythematosus: A Retrospective Single-Center Study.

Abe Yoshiyuki Y Tada Kurisu K Yamaji Ken K Tamura Naoto N

BioMed research international 20210123

<h4>Objectives</h4>Mycophenolate mofetil (MMF) is the standard treatment for lupus nephritis. In Japan, it was approved for lupus nephritis in 2015. We investigated its real-world safety and effectiveness in Japanese patients with systemic lupus erythematosus (SLE).<h4>Methods</h4>We analyzed the continuation rate, adverse events, and reasons for discontinuation of MMF in Japanese patients with SLE in a retrospective single-center study. We included 119 patients who received MMF from 31 July 201 ...[more]

PMID: 33564682

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Project description:BackgroundSystemic lupus erythematosus (SLE) is a clinically and biologically heterogeneous autoimmune disease. We explored whether the deconvolution of whole blood transcriptomic data could identify differences in predicted immune cell frequency between active SLE patients, and whether these differences are associated with clinical features and/or medication use.MethodsPatients with active SLE (BILAG-2004 Index) enrolled in the BILAG-Biologics Registry (BILAG-BR), prior to change in therapy, were studied as part of the MASTERPLANS Stratified Medicine consortium. Whole blood RNA-sequencing (RNA-seq) was conducted at enrolment into the registry. Data were deconvoluted using CIBERSORTx. Predicted immune cell frequencies were compared between active and inactive disease in the nine BILAG-2004 domains and according to immunosuppressant use (current and past).ResultsPredicted cell frequency varied between 109 patients. Patients currently, or previously, exposed to mycophenolate mofetil (MMF) had fewer inactivated macrophages (0.435% vs 1.391%, p = 0.001), naïve CD4 T cells (0.961% vs 2.251%, p = 0.002), and regulatory T cells (1.858% vs 3.574%, p = 0.007), as well as a higher proportion of memory activated CD4 T cells (1.826% vs 1.113%, p = 0.015), compared to patients never exposed to MMF. These differences remained statistically significant after adjusting for age, gender, ethnicity, disease duration, renal disease, and corticosteroid use. There were 2607 differentially expressed genes (DEGs) in patients exposed to MMF with over-representation of pathways relating to eosinophil function and erythrocyte development and function. Within CD4 + T cells, there were fewer predicted DEGs related to MMF exposure. No significant differences were observed for the other conventional immunosuppressants nor between patients according disease activity in any of the nine organ domains.ConclusionMMF has a significant and persisting effect on the whole blood transcriptomic signature in patients with SLE. This highlights the need to adequately adjust for background medication use in future studies using whole blood transcriptomics.

Project description:Our recent data showed that signal transducers and activators of transcription 1 (STAT1), adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine 10 (CXCL10) were significantly elevated in a systemic lupus erythematosus (SLE) cohort compared to healthy donors. High and low STAT1 subsets were identified in SLE patient visits. The present study analyzed the correlation of common treatments used in SLE with the levels of these biomarkers.Peripheral blood leukocytes were collected from 65 healthy donors and 103 SLE patients, of whom 60 had samples from two or more visits. Total RNA was isolated and analyzed for the expression of mRNA and microRNA using Taqman real-time polymerase chain reaction (PCR) assays. Relative expression of interferon signature genes, CCL2, and CXCL10 were determined by the ??CT method. Results were correlated with therapy using prednisone, mycophenolate mofetil, and hydroxychloroquine and analyzed by Wilcoxon/Kruskal-Wallis test and Fisher's exact test.CCL2 and CXCL10 were significantly higher in untreated patients compared to treated patients, however, in high STAT1 patient visits there is no significant difference between treated and untreated patients' visits. When comparing linear regression fits of interferon (IFN) score with CCL2 and CXCL10, untreated patients and high STAT1 patients displayed significantly higher slopes compared to treated patients. There was no significant difference between the slopes of high STAT1 and untreated patients indicating that CCL2 and CXCL10 were correlated with type-I IFN in high STAT1 patients similar to that in untreated patients. CCL2 and CXCL10 levels in the high STAT1 subset remained high in treated patient visits compared to those of the low STAT1 subset.Among the biomarkers analyzed, only CCL2 and CXCL10 showed significantly reduced levels in treated compared to untreated SLE patients. STAT1, CCL2, and CXCL10 are potentially useful indicators of therapeutic action in SLE patients. Further work is needed to determine whether high STAT1 levels convey resistance to therapies commonly used to treat SLE and whether STAT1 inhibitors may have therapeutic implication for these patients.

Dataset Information

Real-World Experience of Safety of Mycophenolate Mofetil in 119 Japanese Patients with Systemic Lupus Erythematosus: A Retrospective Single-Center Study.

Objectives

Methods

Results

Conclusions

Publications

Real-World Experience of Safety of Mycophenolate Mofetil in 119 Japanese Patients with Systemic Lupus Erythematosus: A Retrospective Single-Center Study.

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