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Renal Failure 2023This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
METHODS
A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
RESULTS
The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
CONCLUSIONS
Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
Topics: Humans; Lupus Nephritis; Cyclophosphamide; Induction Chemotherapy; Network Meta-Analysis; Treatment Outcome; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 38087473
DOI: 10.1080/0886022X.2023.2290365 -
European Journal of Paediatric... Jan 2019Available data on mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX) for paediatric-onset anti-N-methyl-d-aspartate receptor encephalitis...
BACKGROUND
Available data on mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX) for paediatric-onset anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is limited.
METHODS
Systematic literature review on patients treated with MMF/AZA/MTX for paediatric-onset anti-NMDARE, with focus on modes of use, efficacy and safety.
RESULTS
87 patients were included (age at onset median 11 years, range 0.8-18 years; 69% females). 46% had a relapsing course. 52% received MMF, 27% AZA, 15% MTX, and 6% a combination of MMF/AZA/MTX (7 patients received intrathecal MTX). Before MMF/AZA/MTX, 100% patients received steroids, 83% intravenous immunoglobulin and 45% plasma exchange, and 50% received second-line treatments (rituximab/cyclophosphamide). MMF/AZA/MTX were administered >6 months from onset in 51%, and only after relapse in 40%. Worst mRS before MMF/AZA/MTX was median 4.5 (range 3-5). At last follow-up (median 2 years, range 0.2-8.6), median mRS was 1 (range 0-6). Median annualised relapse rate was 0.4 (range 0-6.7) pre-MMF/AZA/MTX (excluding first events), and 0 on MMF/AZA/MTX (mean 0.03, range 0-0.8). 7% patients relapsed on MMF/AZA/MTX. These relapsing patients had low rate of second-line treatments before MMF/AZA/MTX (25%), long median time between onset and MMF/AZA/MTX usage (18 months), and frequently they were started on MMF/AZA/MTX only after relapse (75%). Relapse rate was lower among patients who received first immune therapy ≤30 days (25%) than later (64%), who received second-line treatments at first event (14%) rather than not (64%), who were started on MMF/AZA/MTX after the first (12%) rather than subsequent events (17%), and who were started on MMF/AZA/MTX ≤3 months from onset (33%) rather than later (53%). Adverse reactions to MMF/AZA/MTX occurred in 2 cases (cytomegalovirus colitis and respiratory infection), of grade 3 Common Terminology Criteria for Adverse Events v4.0.
DISCUSSION
Our literature review disclosed heterogeneity in the use of MMF/AZA/MTX in paediatric-onset anti-NMDARE. MMF/AZA/MTX usage is mostly restricted to retrospective cohort descriptions. These agents may reduce risk of relapse, and have a reasonable safety profile, however data on larger cohorts are required to definitively determine effect.
Topics: Adolescent; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Azathioprine; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Infant; Male; Methotrexate; Mycophenolic Acid
PubMed: 30318435
DOI: 10.1016/j.ejpn.2018.09.008 -
The Cochrane Database of Systematic... Sep 2015Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions comprises steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This an update of a review first published in 2008.
OBJECTIVES
To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register up to 27 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes.
MAIN RESULTS
Thirty one studies (2217 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large transnational study groups.Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at three months (2 studies: RR 0.43, 95% CI 0.23 to 0.78) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72). Four studies (300 patients) compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leucopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in granulomatosis with polyangiitis.
AUTHORS' CONCLUSIONS
Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil were also effective. Azathioprine, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
Topics: Acute Kidney Injury; Adult; Azathioprine; Cyclophosphamide; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Failure, Chronic; Plasma Exchange; Randomized Controlled Trials as Topic; Vasculitis
PubMed: 26400765
DOI: 10.1002/14651858.CD003232.pub3 -
Journal of Clinical Medicine Sep 2021Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce.... (Review)
Review
Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We aimed to explore three areas: (1) outcome and clinical course; (2) immunological response after COVID-19 in LT recipients; and (3) vaccination response. After systematic selection, 35, 4, and 5 articles, respectively, were considered suitable for each area of analysis. Despite the heterogeneity of the reports included in this study, we found that gastrointestinal symptoms were common in LT recipients. The outcome of the LT population was not per se worse compared to the general population, although careful management of immunosuppressive therapy is required. While a complete therapy discontinuation is not encouraged, caution needs to be taken with use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Although data conflicted about acquired immunity after SARS-CoV-2 infection, vaccine immunogenicity appeared to be low, suggesting that the level of surveillance should be kept high in this population.
PubMed: 34501463
DOI: 10.3390/jcm10174015 -
Multiple Sclerosis and Related Disorders Oct 2021Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune astrocyte disease that mainly affects the optic nerve and spinal cord resulting in blindness or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune astrocyte disease that mainly affects the optic nerve and spinal cord resulting in blindness or paralysis. Mycophenolate mofetil (MMF) is one of the available immunotherapies with purported beneficial effects for patients with NMOSD. The present review aimed to conduct an update systematic review and meta-analysis for the efficacy of mycophenolate mofetil in the treatment of NMOSD and analyze main factors affecting the efficacy of mycophenolate mofetil.
METHODS
The following Medical Subject Heading (MeSH) and related entry terms are used to search English literature in PubMed, MEDLINE and CENTRAL databases, respectively. MeSH include: Neuromyelitis optic and Mycophenolic Acid; entry terms include: NMO Spectrum Disorder, NMO Spectrum Disorders, Neuromyelitis Optica (NMO) Spectrum Disorder, Neuromyelitis Optica Spectrum Disorders, Devic Neuromyelitis Optica, Neuromyelitis Optica, Devic, Devic's Disease, Devic Syndrome, Devic's Neuromyelitis Optica, Neuromyelitis Optica (NMO) Spectrum Disorders, Mycophenolate Mofetil, Mofetil, Mycophenolate, Mycophenolic Acid Morpholinoethyl Ester, Cellcept, Mycophenolate Sodium, Myfortic, Mycophenolate Mofetil Hydrochloride, Mofetil Hydrochloride, Mycophenolate, RS 61,443, RS-61,443, RS61443; (note: literature retrieval operators "AND" "OR" "NOT" are used to link MeSH with Entry Terms.) 30 studies were included in this systematic review and 14 studies were included in meta-analysis. The main efficacy indicators were the difference of the annualized relapse rate (ARR) between before and after mycophenolate mofetil treatments.
RESULTS
In 14 studies involving 930 patients (815 women, 115 men), the ARR were reduced by an average of -1.17 (95%CI, -1.28 to -1.07).
CONCLUSION
Our systematic review and update meta-analysis provide new evidences that mycophenolate mofetil can substantially reduce ARR ratio.
Topics: Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Neuromyelitis Optica; Optic Nerve
PubMed: 34365314
DOI: 10.1016/j.msard.2021.103181 -
Orphanet Journal of Rare Diseases Jun 2019Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea,... (Review)
Review
BACKGROUND
Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. Clinical course without treatment may result in serious disability or death. A review of treatment and its response is still pending.
RESULTS
Sixty-four cases of Satoyoshi syndrome were published between 1967 and 2018. 47 cases described the treatment administered. Drugs used can be divided into two main groups of treatment: muscle relaxants/anticonvulsants, and corticosteroids/immunosuppressants. Dantrolene improved muscle symptoms in 13 out of 15 cases, but not any other symptoms of the disease. Other muscle relaxants or anticonvulsant drugs showed little or no effect. 28 out of 30 cases responded to a regimen that included costicosteroids. Other immunosuppressive drugs including cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus and cyclophosphamide were used to decrease corticosteroid dose or improve efficacy. Immunoglobulin therapy was used in nine patients and four of them obtained a favorable response.
CONCLUSION
Corticosteroids was the most widely treatment employed with the best results in Satoyoshi syndrome. Further studies are needed to determine optimal dose and duration of corticosteroids as well as the role of other immunosuppressants and immunoglobulin therapy. Genetic or autoimmune markers will be useful to guide future therapies.
Topics: Adrenal Cortex Hormones; Alopecia; Animals; Anticonvulsants; Bone and Bones; Dantrolene; Diarrhea; Female; Humans; Immunization, Passive; Immunosuppressive Agents; Male; Rare Diseases; Spasm
PubMed: 31217029
DOI: 10.1186/s13023-019-1120-7 -
Nephrology, Dialysis, Transplantation :... Oct 2022Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance.
METHODS
Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected.
RESULTS
From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%.
CONCLUSIONS
In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.
Topics: Humans; Mycophenolic Acid; Antibodies, Antineutrophil Cytoplasmic; Peroxidase; Immunosuppressive Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Remission Induction
PubMed: 34910216
DOI: 10.1093/ndt/gfab357 -
Acta Obstetricia Et Gynecologica... Sep 2021Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the...
INTRODUCTION
Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.
MATERIAL AND METHODS
The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.
RESULTS
A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.
CONCLUSIONS
Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.
Topics: DNA Damage; Ganciclovir; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Spermatozoa
PubMed: 33755191
DOI: 10.1111/aogs.14151 -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
Journal of Ethnopharmacology Apr 2024Lupus Nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). However, the treatment of lupus nephritis using traditional Chinese medicine... (Meta-Analysis)
Meta-Analysis
ETHNOPHARMACOLOGICAL RELEVANCE
Lupus Nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). However, the treatment of lupus nephritis using traditional Chinese medicine remains controversial.
AIM OF THE STUDY
To assess the efficacy and safety of Shenqi Dihuang decoction in the treatment of LN and review the clinical guidelines.
MATERIALS AND METHODS
Six databases (China National Knowledge Infrastructure, Wanfang, PubMed, China Biology Medicine, the Cochrane Library, and Embase) were searched from their inception to September 10, 2022, for randomized controlled trials on the treatment of lupus nephritis using Shenqi Dihuang decoction. We conducted a meta-analysis of random effects using Review Manager 5.4 and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
RESULTS
A total of 15,790 citations were identified, from which 14 eligible randomized controlled trials that enrolled 1002 participants were selected for this systematic review. Low-to-moderate certainty of evidence indicated that when compared with Western medicine, Shenqi Dihuang decoction combined with Western medicine was associated with favorable effects on clinical efficacy (risk ratio (RR) = 1.25, 95% confidence interval (CI): 1.15-1.37), vascular endothelial growth factor (mean difference (MD) = -30.90, 95% CI: -40.18 to -21.63), serum level (MD = -4.81 μmol L, 95% CI: -17.14 to 7.53), complement C3 (MD = -0.14 g L, 95% CI: -0.23 to -0.04), erythrocyte sedimentation rate (MD = -11.87 mm h, 95% CI: -22.01 to -1.73), and SLE disease activity score (MD = -3.38, 95% CI: -4.15 to -2.61), and exhibited a lower risk of infection (RR = 0.2, 95% CI: 0.05-0.90), gastrointestinal reaction (RR = 0.47, 95% CI: 0.17-1.28), and insomnia (RR = 0.29, 95% CI: 0.09-0.92).
CONCLUSIONS
This systematic review provides a potential reference for understanding the efficacy and safety of Shenqi Dihuang decoction combined with Western medicine for treating patients with lupus nephritis. However, owing to the limited quality of the studies included in this review, lack of mycophenolate mofetil control, and high heterogeneity among the included studies, the current findings should be interpreted with caution. Therefore, the efficacy and safety of Shenqi Dihuang decoction in patients with PN still require further verification through future high-quality clinical studies.
Topics: Humans; Drugs, Chinese Herbal; Lupus Erythematosus, Systemic; Lupus Nephritis; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 38158100
DOI: 10.1016/j.jep.2023.117602