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Clinical Rheumatology Feb 2024Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP.
METHODS
We systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design.
RESULTS
Nine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly.
CONCLUSION
This systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/.
Topics: Humans; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Prospective Studies; Steroids; Immunosuppressive Agents
PubMed: 37981614
DOI: 10.1007/s10067-023-06820-4 -
Rheumatology International Jul 2017The purpose of this study is to assess the effectiveness of mycophenolate mofetil (MMF) in treating Takayasu arteritis (TA) patients. Embase, Cochrane Library, Pubmed,... (Meta-Analysis)
Meta-Analysis Review
The purpose of this study is to assess the effectiveness of mycophenolate mofetil (MMF) in treating Takayasu arteritis (TA) patients. Embase, Cochrane Library, Pubmed, Clinicaltrials. Gov and three Chinese literature databases (VIP, CNKI, WanFang) were searched; randomized-controlled trials and observational studies that compared the efficacy before and after treatment with MMF were included. The efficacy outcomes were disease activity, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) values and steroid dosage. The results were expressed as mean differences with 95% confidence intervals. Compared with the baseline, there were significant reductions in the ESR (-14.92 [25.35, -4.48]), CRP values (-12.99 [-23.29, -2.68]) and the steroid dosage (-17.64 [-24.89, -10.4]) after the addition of MMF, and the disease tended to stabilize. Therefore, MMF might be an alternative immunosuppressive drug for TA for the control of disease activity and to taper the steroid dosage.
Topics: Adolescent; Adult; Biomarkers; Blood Sedimentation; C-Reactive Protein; Chi-Square Distribution; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Steroids; Takayasu Arteritis; Treatment Outcome; Young Adult
PubMed: 28364217
DOI: 10.1007/s00296-017-3704-7 -
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 -
Arthritis Research & Therapy 2006Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus.... (Meta-Analysis)
Meta-Analysis Review
Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Efficacy and adverse event outcomes were sought. Five randomised trials enrolled patients with World Health Organization (WHO) class III, IV, or V (mostly IV) lupus nephritis, predominantly comparing MMF (1 to 3 g daily) with cyclophosphamide and steroid. Complete response and complete or partial response was significantly more frequent with MMF than with cyclophosphamide, with numbers needed to treat of 8 (95% confidence interval 4.3 to 60) to induce one additional complete or partial response, with wide confidence intervals. Death was reported less frequently with MMF (0.7%, 1 death in 152 patients) than with cyclophosphamide (7.8%, 12 deaths in 154 patients), with a number needed to treat to prevent (NNTp) one death of 14 (8 to 48). Hospital admission was also lower with MMF (1.7% versus 15%; NNTp 7.4 [4.8 to 16]). Serious infections, leucopaenia, amenorrhoea, and hair loss were all significantly less frequent with MMF than with cyclophosphamide, but diarrhoea was significantly more common with MMF. Ten of 18 cohort studies enrolled only patients with lupus nephritis (author-defined or WHO class III to V). Seven of these 10 reported that complete or partial response with MMF (mostly 1 or 2 g daily) with steroid occurred in 121/151 (80%) and that treatment failure or no response occurred in 30/151 (20%). Adverse events were generally similar in cohort studies with and without only patients with lupus nephritis. In all 18 cohorts, gastrointestinal adverse events (diarrhoea, nausea, vomiting) occurred in 30%, infection in 23%, and serious infection in 4.3%. Adverse event discontinuations occurred in 14% and lack of efficacy occurred in 10%. There was a single death with MMF, a mortality rate over the course of 1 year of approximately 0.2%. The results form a basis on which to plan future studies and provide a guide for the use of MMF in lupus nephritis until results of larger studies are available. At least one such study is under way.
Topics: Cohort Studies; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 17163990
DOI: 10.1186/ar2093 -
Innovations in Clinical Neuroscience 2022Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic... (Review)
Review
Comparative Analysis of Treatment Outcomes in Patients with Neuromyelitis Optica Spectrum Disorder Treated with Rituximab, Azathioprine, and Mycophenolate Mofetil: A Systematic Review and Meta-analysis.
INTRODUCTION
Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and tolerability of rituximab (RTX) in comparison to azathioprine (AZT) and mycophenolate mofetil (MMF) for the treatment of NMOSD.
METHODS
A systematic search was conducted among electronic databases, including PubMed, Scopus, EBSCO, and Cochrane, for relevant studies. We included randomized, controlled trials and prospective and retrospective studies evaluating the efficacy and safety of RTX compared to AZT and/or MMF in adult and pediatric patients with NMOSD. The Newcastle-Ottawa Scale (NOS) and Cochrane Collaboration tool were used to determine the risk of bias.
RESULTS
Eleven studies involving 1,086 patients were included in our study. Treatment with RTX generally yielded favorable annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) results in comparison to AZT and MMF, despite its variable statistical significance. RTX treatment reduced the relapse rate and hazard risk for relapse (HRR). Patients in the RTX group experienced significantly fewer adverse events, among which the most common were allergies, infections, and leukopenia.
CONCLUSION
In this study, RTX appeared to be superior to AZT and MMF in improving disability and reducing relapse in patients with NMOSD. RTX is also associated with fewer adverse events based on pooled analysis. Future randomized clinical trials are needed to establish the efficacy and safety of RTX in patients with NMOSD.
PubMed: 35958974
DOI: No ID Found -
PloS One 2015Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use in systemic sclerosis (SSc) since gastrointestinal involvement is common. The objective of this study is to evaluate gastrointestinal adverse events of mycophenolate in SSc. Secondarily we evaluated other adverse events, and the effectiveness of mycophenolate in skin and lung disease.
METHODS
A literature search of Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL (inception-2013) was performed. Studies reporting use of mycophenolate in SSc patients, adverse events, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusing capacity of carbon monoxide (DLCO) were included. The primary outcome was gastrointestinal events occurring after the initiation of mycophenolate. Secondary safety outcomes included myelosuppression, infection, malignancy, and death after the initiation of mycophenolate.
RESULTS
617 citations were identified and 21 studies were included. 487 patients were exposed to mycophenolate. The mean disease duration ranged between 0.8-14.1 years. There were 18 deaths and 90 non-lethal adverse events. The non-lethal adverse events included 43 (47.7%) gastrointestinal events, 34 (26%) infections, 6 (5%) cytopenias and 2 (2%) malignancies. The most common gastrointestinal events included diarrhea (n=18 (14%)), nausea (n=12 (9%)), and abdominal pain (n=3 (2%)). The rate of discontinuation ranged between 8%-40%. Seven observational studies reported improvement or stabilization in FVC, and 5 studies report stabilization or improvement in MRSS.
CONCLUSION
Mycophenolate-associated gastrointestinal adverse events are common in SSc, but not severe enough to preclude its use. Observational data suggests mycophenolate may be effective in improving or stabilizing interstitial lung disease, and skin involvement.
Topics: Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Mycophenolic Acid; Respiratory Function Tests; Scleroderma, Systemic; Skin; Treatment Outcome
PubMed: 25933090
DOI: 10.1371/journal.pone.0124205 -
Medicine Jul 2010We performed a systematic review and meta-analysis of randomized controlled trials to compare complete remission and adverse events (that is, infection, leukopenia, and... (Comparative Study)
Comparative Study Meta-Analysis Review
We performed a systematic review and meta-analysis of randomized controlled trials to compare complete remission and adverse events (that is, infection, leukopenia, and gastrointestinal [GI] symptoms) between mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for the treatment of lupus nephritis (LN). We identified trials from MEDLINE using the PubMed and Ovid search engines, and from The Cochrane Central Register of Randomized Controlled Trials. Eligible studies were randomized controlled trials comparing MMF with CYC with 1 of following outcomes: complete remission, complete/partial remission, infection, leukopenia, GI symptoms, serum creatinine, 24-hour urine protein, and urine albumin. Data were independently extracted by 2 reviewers. Five trials with a total of 638 patients were eligible for review. While the MMF group tended to achieve complete remission more frequently than the CYC group, this was not significant (pooled risk ratio [RR], 1.60; 95% confidence interval [CI], 0.87-2.93). Pooling based on the 4 homogeneous trials yielded similar results-that is, no benefit of MMF compared with CYC groups (RR, 1.15; 95% CI, 0.74-1.77). The complete or partial remission rates were also not different (pooled RR, 1.21; 95% CI, 0.97-1.48) among the groups. The adverse events (infection, renal function, and GI symptoms) were not significantly different, except for leukopenia, which was lower in the MMF group. In summary, patients treated with MMF and CYC had similar remission rates, but the MMF group had less frequent leukopenia than the CYC group. Further large-scale trials are needed to confirm these results.
Topics: Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 20616662
DOI: 10.1097/MD.0b013e3181e93d00 -
Medicine Sep 2020Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for LN.
METHODS
Relevant literature was searched by computer from the establishment of the database to November 2019. A meta-analysis was conducted to analysis the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients. The primary end-point was response to urine protein, serum creatinine (Scr) and serum complement C3, and the secondary end-points were complete remission and adverse reactions.
RESULTS
Eighteen articles were selected for the final meta-analysis, involving 1989 patients with LN, of which the renal biopsy result could be classified into class III-V according to the standards of WHO/ISN. The results revealed that MMF was superior to CYC in increasing the level of serum complement C3 [SMD = 0.475, 95%CI (0.230-0.719)] and complete remission [RR = 1.231, 95%CI (1.055-1.437)]. Furthermore, the subgroup analysis showed that it was in Asian patients, rather than in Caucasian patients, that CYC exerted a better effect on lowering the level of urine protein (UPRO) than MMF [SMD = 0.405, 95%CI (0.081-0.730)]. Besides, when the initial UPRO level was less than 4 g/day, the effect of CYC was better than MMF [SMD = 0.303, 95%CI (0.014-0.591)]. There was no significant difference between MMF and CYC in improving Scr [SMD = 0.090, 95%CI (-0.060-0.239)]. When it came to the comparison of safety between MMF and CYC, the meta-analysis showed that MMF was superior to CYC in decreasing infection in Caucasian patients [RR = 0.727, 95%CI (0.532-0.993)], reducing the risk of leukopenia and menstrual abnormalities in Asian patients and lowering the frequency of gastrointestinal symptoms [RR = 0.639, 95%CI (0.564-0.724)], independent of race.
CONCLUSIONS
MMF precedes CYC in improving serum complement C3 and complete remission regardless of race, as well as shows fewer adverse drug reactions in the induction treatment of LN belonging to type III-V. But for Asian patients or those initial UPRO levels are less than 4 g/day, CYC may be superior to MMF.
Topics: Adult; Cyclophosphamide; Female; Humans; Lupus Nephritis; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 32957400
DOI: 10.1097/MD.0000000000022328 -
Computational Intelligence and... 2022Mizoribine (MZR) is widely used in Asia due to its high safety and low cost, and comparative studies of its safety and efficacy with the first-line drug mycophenolate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mizoribine (MZR) is widely used in Asia due to its high safety and low cost, and comparative studies of its safety and efficacy with the first-line drug mycophenolate mofetil (MMF) have been carried out. This paper aimed to compare the efficacy and safety of MZR and MMF in immunosuppressive therapy of renal transplantation by meta-analysis.
METHODS
We searched randomized controlled trials (RCTs) comparing MZR versus MMF for renal transplantation in PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM). Articles were assessed for their risk of bias using the Cochrane Collaboration. Forest plots and funnel plots were also performed on the included articles.
RESULTS
A total of twelve studies with 1103 patients were selected in the analysis. No significant difference were observed between the MZR group and the MMF group for the rate of acute rejection (RR = 1.50, 95% CI 1.11 to 2.01, = 0.008), patient survival (RR = 1.01, 95% CI 0.99 to 1.03, = 0.56), graft survival (RR = 1.02, 95% CI 1.00 to 1.04, = 0.12), leucopenia (RR = 0.69, 95% CI 0.44 to 1.10, = 0.12), and liver damage (RR = 0.72, 95% CI 0.46 to 1.13, = 0.15). The MZR group was associated with a lower risk of gastrointestinal disorder (RR = 0.28, 95% CI 0.13 to 0.62, = 0.002) and cytomegalovirus infection (RR = 0.59, 95% CI 0.42 to 0.84, = 0.003) but had a higher risk of hyperuricemia (RR 1.79, 95% CI 1.17 to 2.75, = 0.007). No significant publication bias was observed among included studies. . MZR is similar to MMF in efficacy, and in terms of safety, MZR has a lower risk of gastrointestinal disorder and cytomegalovirus infection but a higher risk of hyperuricemia.
Topics: Cytomegalovirus Infections; Gastrointestinal Diseases; Humans; Hyperuricemia; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Ribonucleosides
PubMed: 35909831
DOI: 10.1155/2022/5717068 -
The Cochrane Database of Systematic... Oct 2010Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005.
OBJECTIVES
To assess treatments for bullous pemphigoid.
SEARCH STRATEGY
In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers.
SELECTION CRITERIA
Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two authors evaluated the studies for the inclusion criteria, and extracted data independently.
MAIN RESULTS
We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12).
AUTHORS' CONCLUSIONS
Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.
Topics: Azathioprine; Clobetasol; Combined Modality Therapy; Drug Therapy, Combination; Drugs, Chinese Herbal; Glucocorticoids; Humans; Immunosuppressive Agents; Niacinamide; Pemphigoid, Bullous; Plasma Exchange; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Tetracycline
PubMed: 20927731
DOI: 10.1002/14651858.CD002292.pub3