Mycophenolate Mofetil and Steroid for Treatment of Patients With IgA Nephropathy.
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SUBMITTER: Miao J
PROVIDER: S-EPMC10831348 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Mycophenolate Mofetil and Steroid for Treatment of Patients With IgA Nephropathy.
Miao Jing J Duriseti Parikshit P Radhakrishnan Yeshwanter Y Vaughan Lisa L Fervenza Fernando C FC Zand Ladan L
Kidney international reports 20231020 1
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Project description:BackgroundIgA nephropathy is the most common primary glomerular disease worldwide and also the most frequent cause of kidney failure. Mycophenolate mofetil (MMF) is a selective immunosuppressant widely used in many autoimmune diseases. However, the benefits and risks of MMF for the treatment of IgA nephropathy remain uncertain.MethodsA systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to assess the efficacy and safety of MMF in IgA nephropathy patients, using the statistical software Review Manager 5.1.ResultsEight RCTs involving 357 patients were identified and included in this review. Overall, no statistical difference was found in the therapeutic effect of MMF treatment compared with other therapies. MMF had no significant effects on reducing proteinuria or protecting renal function. However, subgroup analysis indicated that relatively short-term therapy (<18 months) might be beneficial in IgA nephropathy patients while longer term MMF use conferred no advantage. There was also no statistical difference between MMF and control groups in the incidence of side effects. When compared with other immunosuppressants, MMF was considered superior to cyclophosphamide in terms of better therapeutic effects and fewer adverse reactions, but no difference was found between MMF and leflunomide.ConclusionsOur current evidence indicates that a relatively short course of MMF may be beneficial in treating IgA nephropathy. However, high-quality RCTs with large sample size as well as a well-designed study to evaluate the long-term effects of MMF are needed to further evaluate the efficacy and safety of MMF in this disease.
| S-EPMC4267433 | biostudies-literature
Project description:Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Mycophenolate mofetil (MMF) has an anti-inflammatory effect, inhibiting lymphocyte proliferation. Previous studies showed attenuation of diabetic nephropathy with MMF, but the underlying mechanisms were unclear. This study aimed to identify the effect of MMF on diabetic nephropathy and investigate its action mechanisms in type 2 diabetic mice model. Eight-week-old db/db and control mice (db/m mice) received vehicle or MMF at a dose of 30 mg/kg/day for 12 weeks. MMF-treated diabetic mice showed decreased albuminuria, attenuated mesangial expansion, and profibrotic mRNA expressions despite the high glucose level. The number of infiltrated CD4(+) and CD8(+) T cells in the kidney was significantly decreased in MMF-treated db/db mice and it resulted in attenuating elevated intrarenal TNF-α and IL-17. The renal chemokines expression and macrophages infiltration were also attenuated by MMF treatment. The decreased expression of glomerular nephrin and WT1 was recovered with MMF treatment. MMF prevented the progression of diabetic nephropathy in db/db mice independent of glycemic control. These results suggest that the effects of MMF in diabetic nephropathy are mediated by CD4(+) T cell regulation and related cytokines.
| S-EPMC4539432 | biostudies-literature
Project description:Background: Only a subset of patients with systemic sclerosis (SSc) demonstrate improvement in modified Rodnan skin score (mRSS) during mycophenolate mofetil (MMF) treatment. Here we investigated the molecular and cellular effects in skin associated with MMF therapy in subjects who demonstrated or lacked clinical improvement. Methods: Clinical and skin gene expression data were obtained genome-wide from baseline and longitudinal (6-, 12-, 24-, and 36-mo) biopsies in 33 MMF-treated subjects with SSc. Clinical improvement was defined as mRSS reduction ≥ 25%. An inflammatory signature score was calculated for each patient sample using single-sample gene set enrichment analysis (ssGSEA). Cell type specific changes during treatment were characterized. Results: Eleven subjects with SSc completed at least 24 months of MMF therapy and were termed ‘completers’. Two distinct gene expression patterns were observed that corresponded to MMF treatment status. Three subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in activated dendritic cells. MMF cessation at 24 months resulted in an inflammatory signature rebound paralleling mRSS increase. Three subjects that remained on MMF showed persistent inflammatory signature reductions with decreasing or stable mRSS. The remaining six completers either did not fulfill minimum mRSS (n=5), and/or lacked a baseline inflammatory signature (n=4). Conclusions: An elevated inflammatory skin gene expression signature is associated with clinical improvement during MMF therapy. Inflammation returned upon MMF discontinuation with concomitant mRSS increase. These data summarize MMF’s molecular effects in skin and support MMF therapy for longer than 24 months in patients who demonstrate clinical response.
2017-01-01 | GSE76885 | GEO
Project description:•Posterior reversible encephalopathy syndrome is one of the numerous causes of status epilepticus and it should be kept in mind while encountering such clinical scenario.•Mycophenolate mofetil can be contributory cause of PRES.•Prompt recognition and timely intervention is a key to full recovery without any residual neurological deficits after refractory status epilepticus.
| S-EPMC7895702 | biostudies-literature
Project description:ObjectiveTo describe the effects of the anti-tumor necrosis factor neutralizing antibody, infliximab, and the antiproliferative immunosuppressant, mycophenolate mofetil, in refractory neurosarcoidosis.MethodsWe treated patients with biopsy-proven sarcoidosis and CNS involvement, who had failed treatment with steroids, with infliximab (5 mg/kg on weeks 0, 2, and 6, and then every 6-8 weeks thereafter). Six out of seven patients were co-treated with mycophenolate mofetil (1,000 mg PO BID). Patients underwent a review of symptoms and complete neurologic examination every 3 months and MRI scanning before and after 3-4 infusions of infliximab.ResultsAll patients reported significant symptomatic improvement by the fourth infusion of infliximab, including relief of headache and neuropathic pain, reversal of motor, sensory, or coordination deficits, and control of seizure activity. Furthermore, infliximab therapy was universally associated with a decrease in lesion size or suppression of gadolinium enhancement as documented by MRI. A positive treatment response was attained irrespective of location or distribution of CNS involvement by sarcoidosis (dural/leptomeningeal based vs intraparenchymal; cord vs brain; single lesion vs multifocal). There were no serious adverse effects in a follow-up period spanning 6-18 months.ConclusionsCombination treatment with mycophenolate mofetil and infliximab is a promising therapeutic approach for neurosarcoidosis.
| S-EPMC2677503 | biostudies-literature
Project description:BackgroundMedically refractory Crohn's disease (CD) is associated with a high risk of complications. Mycophenolate mofetil (MMF), a small molecule immunosuppressant, has limited data in patients with CD, and objective endoscopic response to MMF has not been reported.AimsWe evaluated the safety and clinical, endoscopic, and biochemical effectiveness of off-label MMF for refractory CD as monotherapy or in combination with a biologic in patients with CD.MethodsWe retrospectively assessed adverse events (AEs), clinical response (Harvey-Bradshaw index), endoscopic response (simple endoscopic score in Crohn's disease), and physician global assessment at an academic medical center and county hospital.Results60 patients received MMF as monotherapy (n = 40) or in combination with a biologic (n = 20) between 2008 and 2021 at a dose ranging from 1000 to 4000 mg daily. Median age was 39 years and median disease duration was 12 years. All patients previously failed ≥ 1 advanced therapy (median = 4). The median MMF therapy duration was 27 weeks. 54% achieved clinical response and 19% achieved clinical remission after a mean of 19.5 weeks (SD 14.5). Endoscopic response occurred in 32%, endoscopic remission in 16%, and endoscopic healing in 4% after a mean of 46.6 weeks (SD 31.0). 48% of patients experienced AEs, most commonly mild infection, nausea/vomiting, and headache. One serious AE occurred, which was assessed as unrelated to MMF.ConclusionsMMF resulted in clinical, endoscopic, and biochemical benefits in some patients with refractory CD, and was tolerated by most patients. Further randomized controlled trials are needed to define optimal dosing and long-term efficacy and safety.
| S-EPMC11655623 | biostudies-literature
Project description:BackgroundRituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient).ResultsTTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups.ConclusionsAdministration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.
| S-EPMC8819987 | biostudies-literature
Project description:Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
| S-EPMC2678035 | biostudies-literature
Project description:PurposeTo evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases.DesignRetrospective cohort study.MethodsCharacteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each.ResultsAmong 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation--sustained over consecutive visits spanning at least 28 days--was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy.ConclusionsGiven sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment-limiting side effects were observed in 12% of patients and typically were reversible.
| S-EPMC2826576 | biostudies-literature
Project description:PurposeSub-analysis of the FAST Trial comparing change in CD4 (∆CD4) from baseline through 12 months in uveitis patients treated with mycophenolate mofetil (MMF) and methotrexate (MTX).MethodsPatients were randomly allocated to 1.5 g twice daily MMF or 25 mg weekly MTX. Individuals with CD4 counts at baseline, 6 months (or treatment failure prior), and 12 months (or treatment failure between 6 and 12 months) were included. The association between treatment and ∆CD4 (cells/μL) was analyzed using multivariable linear regression.ResultsThere was no significant difference in ∆CD4 between MMF and MTX at 6 months (-31.7 cells/μL for MMF compared to MTX; 95% CI: -358.2 to 294.8, P = .85) and 12 months (-78.3 cells/μL for MMF compared to MTX; 95% CI: -468.0 to 311.3; P = .69).ConclusionThere was no significant difference in ∆CD4 between MMF and MTX from baseline to 12 months, suggesting that MMF does not confer additional risk of CD4 lymphopenia in uveitic patients.ClinicalTrials.gov Identifier: NCT01829295.
| S-EPMC7876156 | biostudies-literature