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Transplant Infectious Disease : An... Aug 2009Mycophenolate mofetil (MMF) is one of the most frequently used immunosuppressive drugs in solid organ transplant recipients. MMF is an inhibitor of... (Review)
Review
Mycophenolate mofetil (MMF) is one of the most frequently used immunosuppressive drugs in solid organ transplant recipients. MMF is an inhibitor of inosine-5'-monophosphate, and is able to preferentially inhibit B-cell and T-cell function. The immunosuppressive abilities of MMF have made it one of the most successful anti-rejection drugs in transplant patients, but patients also appear to have increased susceptibility to infections, specifically cytomegalovirus and BK virus. Despite its association with an increased risk of infection, MMF has also exhibited antimicrobial activity against pathogens including hepatitis C, Pneumocystis jirovecii, and human immunodeficiency virus. A thorough understanding of the functions of MMF on the immune system and interaction with infectious pathogens could be helpful in implementing preventative strategies against opportunistic infections in transplant patients.
Topics: Animals; Antifungal Agents; Antiviral Agents; B-Lymphocytes; Clinical Trials as Topic; Graft Rejection; Humans; Immunosuppressive Agents; Mice; Mycophenolic Acid; Opportunistic Infections; Organ Transplantation; Pneumocystis; Rats; T-Lymphocytes; Viruses
PubMed: 19497072
DOI: 10.1111/j.1399-3062.2009.00407.x -
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 -
Annals of the Rheumatic Diseases Dec 2010
Topics: Azathioprine; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 21097656
DOI: 10.1136/ard.2010.139683 -
Alimentary Pharmacology & Therapeutics Aug 2011Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment.
BACKGROUND
Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment.
AIM
To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes.
METHODS
Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression.
RESULTS
Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001).
CONCLUSIONS
Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.
Topics: Adolescent; Adult; Aged; Child; Cohort Studies; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Netherlands; Retrospective Studies; Severity of Illness Index; Syndrome; Treatment Outcome; Young Adult
PubMed: 21668459
DOI: 10.1111/j.1365-2036.2011.04727.x -
JAMA Dermatology Mar 2022
Topics: Autoimmune Diseases; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 35138336
DOI: 10.1001/jamadermatol.2021.5848 -
Clinical Journal of the American... Mar 2012The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
This observational study prospectively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR.
RESULTS
The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m(2), P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group.
CONCLUSIONS
This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.
Topics: Acute Disease; Adult; Biopsy; Chi-Square Distribution; Chicago; Drug Administration Schedule; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Sirolimus; Tacrolimus; Time Factors; Treatment Outcome
PubMed: 22282478
DOI: 10.2215/CJN.06940711 -
The Cochrane Database of Systematic... Feb 2014Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system and a leading cause of disability in young and middle-aged adults. Mycophenolate... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system and a leading cause of disability in young and middle-aged adults. Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been used for the prevention of allograft rejection after renal, cardiac, or liver transplant and in patients with autoimmune diseases such as active relapsing-remitting (RRMS) and progressive MS.
OBJECTIVES
To assess the efficacy and safety of MMF for preventing disease activity in patients with RRMS.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (January 14, 2013). We searched three Chinese databases (January 2013) and checked reference lists of identified trials. We contacted authors and pharmaceutical companies to ask for additional information. We applied no language restrictions.
SELECTION CRITERIA
We included randomized controlled trials with a follow-up of at least 12 months that compared MMF as monotherapy or in combination with other treatments versus placebo, another drug, or the same cointervention as the treated group.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the trials for inclusion, assessed trial quality, and extracted data.
MAIN RESULTS
One included study involving 26 participants with new-onset RRMS investigated the efficacy and safety of MMF (13 participants) versus placebo in interferon β-1a-treated participants. It was assessed to be at high risk of bias, and had a small numbers of participants receiving treatment with short-term duration. There was inadequate information provided by the study to determine the effect of MMF in reducing relapses, preventing disability progression, or developing new T2- or new gadolinium (Gd)-enhanced lesions on magnetic resonance imaging (MRI) after a 12-month follow-up period. No data were available at 24 months. No serious adverse effects were reported. All participants in the MMF-treated group suffered from gastrointestinal upset, but none of them discontinued therapy as a result.
AUTHORS' CONCLUSIONS
The evidence we found from one small study was insufficient to determine the effects of MMF as an add-on therapy for interferon β-1a in new-onset RRMS participants.
Topics: Adjuvants, Immunologic; Humans; Immunosuppressive Agents; Interferon beta-1a; Interferon-beta; Multiple Sclerosis, Relapsing-Remitting; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 24505016
DOI: 10.1002/14651858.CD010242.pub2 -
Ophthalmology Oct 2014To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis.
DESIGN
Multicenter, block-randomized, observer-masked clinical trial.
PARTICIPANTS
Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India.
INTERVENTION
Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered.
MAIN OUTCOME MEASURES
Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence.
RESULTS
Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31).
CONCLUSIONS
There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.
Topics: Administration, Oral; Adult; Female; Humans; Immunosuppressive Agents; Macular Edema; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Uveitis; Visual Acuity; Young Adult
PubMed: 24917273
DOI: 10.1016/j.ophtha.2014.04.023 -
BMC Nephrology Jul 2017The application of mycophenolate mofetil (MMF) in treating patients with immunoglobulin A nephropathy (IgAN) remains uncertain. This update meta-analysis was performed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The application of mycophenolate mofetil (MMF) in treating patients with immunoglobulin A nephropathy (IgAN) remains uncertain. This update meta-analysis was performed to re-evaluate the therapeutic potential of MMF in IgAN.
METHODS
Articles were obtained by searching the electronic databases without language restriction. Randomized controlled trials studying the role of MMF in treating IgAN were collected. The quality of included studies was critically evaluated. Data analyses were performed by using RevMan 5.3 software.
RESULTS
A total of 297 articles were screened and eight articles were finally included. Among the eight randomized controlled trials, five and three were high quality and low quality, respectively. Both fixed-effect and random-effect model were used. Pooled results by combining all the eight studies suggested that IgAN patients in MMF group had a higher remission rate than that in control group. Compared to placebo or corticosteroid monotherapy, MMF monotherapy exerted a higher remission rate and side effect rate in both main analysis and subgroup analysis by human race. Compared to corticosteroid plus other immunosuppressive agent therapy, corticosteroid plus MMF therapy had a higher remission rate, lower serum creatinine doubling rate, progression to end-stage renal disease rate and side effects rate. Subgroup analysis by therapeutic regimen further confirmed these results between corticosteroid plus MMF therapy and corticosteroid plus cyclophosphamide therapy. Funnel-plot displayed a symmetrical figure, indicating no publication bias existed.
CONCLUSIONS
MMF has the potential in treatment of IgAN, especially for Asians. The evidence currently available shows that MMF monotherapy has a more efficacy but higher side effects when compared to placebo or corticosteroid monotherapy in treatment of Asians with IgAN. While MMF combined with corticosteroid regimen has a more efficacy and lower side effects when compared with corticosteroid plus cyclophosphamide regimen.
Topics: Antibiotics, Antitubercular; Asian People; Gastrointestinal Diseases; Glomerulonephritis, IGA; Humans; Mycophenolic Acid; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28724421
DOI: 10.1186/s12882-017-0647-x -
Annals of Transplantation Dec 2013Liver transplantation is the only live-saving, curative treatment for various end-stage liver diseases, and it has excellent survival rates. Mycophenolate mofetil is... (Review)
Review
Liver transplantation is the only live-saving, curative treatment for various end-stage liver diseases, and it has excellent survival rates. Mycophenolate mofetil is widely used as co-medication for immunosuppression after liver transplantation, especially to allow a sparing effect on calcineurin-inhibitors, thus reducing their numerous adverse effects. It improves both graft and patient survival. The properties of its active metabolite, mycophenolic acid, are diverse: inhibition of de novo purine synthesis and selective lymphocyte inhibition, anti-tumoral, antiviral, anti-angioneoplastic, and vasculoprotective mechanisms are described and summarized in this review. The most common adverse effects of mycophenolate mofetil are gastrointestinal complaints such as diarrhea, which often lead to dose-reduction or withdrawal of mycophenolate mofetil. A newer, enteric-coated formulation is available, which is meant to reduce the gastrointestinal adverse effects. Mycophenolate mofetil does not relevantly interact with other common drugs. The question of whether therapeutic drug monitoring allows optimized dosing strategies cannot be satisfyingly answered yet. The optimal partner-immunosuppressant seems to be tacrolimus, especially in low doses. This tutorial review provides an overview of recent studies exploring the role of mycophenolate mofetil in liver transplantation with regards to its development, mechanism of action, and actual controversies such as therapeutic drug monitoring or de novo malignancy after transplantation.
Topics: End Stage Liver Disease; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Treatment Outcome
PubMed: 24346057
DOI: 10.12659/AOT.889299