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Cleveland Clinic Journal of Medicine May 2023C3 glomerulopathy (C3G) is a rare kidney disease that causes kidney dysfunction as a result of dysregulation of the complement system alternate pathway (AP). C3G...
C3 glomerulopathy (C3G) is a rare kidney disease that causes kidney dysfunction as a result of dysregulation of the complement system alternate pathway (AP). C3G encompasses 2 separate disorders, C3 glomerulonephritis and dense deposit disease. The presentation and natural history is variable and kidney biopsy is needed to confirm the diagnosis. The overall prognosis is poor with high recurrence rates after transplant. A better understanding of C3G is needed as is high-quality evidence to guide therapy, which currently includes mycophenolate mofetil and steroids for moderate to severe disease, and terminal complement blockade with anti-C5 therapy in unresponsive cases.
Topics: Humans; Kidney Diseases; Kidney; Mycophenolic Acid
PubMed: 37225259
DOI: 10.3949/ccjm.90.e-s1.01 -
The New England Journal of Medicine Nov 2011Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis.
METHODS
We carried out a 36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events.
RESULTS
A total of 227 patients were randomly assigned to maintenance treatment (116 to mycophenolate mofetil and 111 to azathioprine). Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003), and with respect to time to renal flare and time to rescue therapy (hazard ratio, <1.00; P < 0.05). Observed rates of treatment failure were 16.4% (19 of 116 patients) in the mycophenolate mofetil group and 32.4% (36 of 111) in the azathioprine group. Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68). Serious adverse events occurred in 33.3% of patients in the azathioprine group and in 23.5% of those in the mycophenolate mofetil group (P = 0.11), and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil (39.6% vs. 25.2%, P = 0.02).
CONCLUSIONS
Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy. (Funded by Vifor Pharma [formerly Aspreva]; ALMS ClinicalTrials.gov number, NCT00377637.).
Topics: Adolescent; Adult; Aged; Azathioprine; Female; Humans; Immunosuppressive Agents; Infections; Kaplan-Meier Estimate; Lupus Nephritis; Maintenance Chemotherapy; Male; Middle Aged; Mycophenolic Acid; Patient Dropouts; Secondary Prevention; Young Adult
PubMed: 22087680
DOI: 10.1056/NEJMoa1014460 -
Transplant International : Official... May 2015The patent of mycophenolate mofetil (MMF) has expired, and for enteric-coated mycophenolate sodium (EC-MPS), this will happen in 2017. In the twenty years these drugs... (Review)
Review
The patent of mycophenolate mofetil (MMF) has expired, and for enteric-coated mycophenolate sodium (EC-MPS), this will happen in 2017. In the twenty years these drugs have been used, they have become extremely popular. In this review, the reasons for the popularity of mycophenolate are discussed, including the benefits compared to azathioprine. MMF and EC-MPS are therapeutically equivalent. Although neither is considered to be a narrow therapeutic index drug, this should not lead to careless switching between the innovator drug and generic formulations, or between one generic formulation and another. The pipeline of new immunosuppressive drugs is dry, and it is very likely that we will be using mycophenolate for many more years to come as a first-line immunosuppressive drug in our transplant population. Whether or not the development of donor-specific anti-HLA antibodies is related to drug exposure (mycophenolic acid concentrations) remains to be investigated.
Topics: Azathioprine; Clinical Trials as Topic; Drug Monitoring; Drugs, Generic; Genetic Variation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tablets, Enteric-Coated
PubMed: 25758949
DOI: 10.1111/tri.12554 -
Clinical Journal of the American... Sep 2020
Topics: Humans; Immunosuppressive Agents; Kidney Diseases; Mycophenolic Acid
PubMed: 32841154
DOI: 10.2215/CJN.11740720 -
Revista Espanola de Enfermedades... Jun 2022The current edition of the journal features a Spanish, nationwide, multi-institutional study by Gomez Bravo MA et al. exploring the advantages of everolimus...
The current edition of the journal features a Spanish, nationwide, multi-institutional study by Gomez Bravo MA et al. exploring the advantages of everolimus (EVR)-facilitated tacrolimus (TAC) minimization versus TAC in combination with mycophenolate mofetil (MMF) after liver transplantation (LT).
Topics: Drug Therapy, Combination; Everolimus; Humans; Kidney; Liver Transplantation; Multicenter Studies as Topic; Mycophenolic Acid; Tacrolimus
PubMed: 35545915
DOI: 10.17235/reed.2022.8902/2022 -
The British Journal of Dermatology Sep 2022
Topics: Dermatomyositis; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid
PubMed: 35257367
DOI: 10.1111/bjd.21235 -
British Journal of Clinical Pharmacology Jan 2013A number of medications do not have a licence, or label, for use in the paediatric age group nor for the specific indication for which they are being used in children.... (Review)
Review
A number of medications do not have a licence, or label, for use in the paediatric age group nor for the specific indication for which they are being used in children. Over recent years, mycophenolate mofetil has increasingly been used off-label (i.e. off-licence) in adults for a number of indications, including autoimmune conditions; progressively, this wider use has been extended to children. This review summarizes current use of mycophenolate mofetil (MMF) in children, looking at how MMF works, the pharmacokinetics, the clinical conditions for which it is used, the advantages it has when compared with other immunosuppressants and the unresolved issues remaining with use in children. The review aims to focus on off-label use in children so as to identify areas that require further research and investigation. The overall commercial value of MMF is limited because it has now come off patent in adults. Given the increasing knowledge of the pharmacodynamics, pharmacokinetics and pharmacogenomics demonstrating the clinical benefits of MMF, new, formal, investigator-led studies, including trials focusing on the use of MMF in children, would be of immense value.
Topics: Calcineurin Inhibitors; Child; Drug Interactions; Drug Monitoring; Humans; IMP Dehydrogenase; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Off-Label Use; Polymorphism, Genetic
PubMed: 22519685
DOI: 10.1111/j.1365-2125.2012.04305.x -
Rheumatic Diseases Clinics of North... Aug 2014Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients... (Review)
Review
Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that the efficacy of mycophenolate mofetil may be similar to that of quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil.
Topics: Azathioprine; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Ethnopharmacology; Humans; Immunosuppressive Agents; Lupus Nephritis; Medication Therapy Management; Mycophenolic Acid; Organs at Risk; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25034160
DOI: 10.1016/j.rdc.2014.05.001 -
Journal of Ayub Medical College,... 2020Lupus nephritis and its induction therapies are understudied subjects in rheumatology especially in our population. The objective of this study is to compare the renal... (Comparative Study)
Comparative Study
BACKGROUND
Lupus nephritis and its induction therapies are understudied subjects in rheumatology especially in our population. The objective of this study is to compare the renal response to Mycophenolate mofetil (MMF) and Cyclophosphamide (CYC) as induction therapy in the Pakistani population with lupus nephritis.
METHODS
This is a comparative retrospective study conducted at the department of rheumatology, Fauji Foundation Hospital (FFH), Rawalpindi, and the duration of the study was 1.5 years from July 2016 to December 2017. The study includes 28 patients, all females, ages between 18 to 50 years. All have biopsy proven lupus nephritis (LN). All 28 LN patients have either stage III, IV, V. They were investigated and analysed over 1.5 years. 14 patients were given MMF (2.5 gram/day) (MMF group) and 14 patients were given CYC (NIH protocol/monthly) (CYC group) for 24 weeks as induction therapy. Comparison of baseline characteristics, complete and partial renal responses to treatment was seen in the MMF and CYC groups.
RESULTS
Primary end point (complete response) is achieved in 6 (42.85%) in MMF group and 5 (35.71%) in the CYC group. The secondary end point (partial response) was achieved in 5 (35.71%) patients in the MMF group and 6(42.85%) in the CYC group. The difference in the cumulative probability of complete and partial response was not statistically significant between the two groups (P-0.470 for CR) and (p-value 0.132 for PR).
CONCLUSIONS
Mycophenolate mofetil is a new therapy for LN and it has equal efficacy as compared to CYC for LN induction.
Topics: Adolescent; Adult; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lupus Nephritis; Middle Aged; Mycophenolic Acid; Retrospective Studies; Young Adult
PubMed: 33225643
DOI: No ID Found -
American Journal of Transplantation :... Nov 2009Mycophenolate mofetil (MMF) in combination with calcineurin inhibitors (CNIs) has greatly contributed to acute rejection rate reduction. Because of its immunosuppressive... (Review)
Review
Mycophenolate mofetil (MMF) in combination with calcineurin inhibitors (CNIs) has greatly contributed to acute rejection rate reduction. Because of its immunosuppressive potency it was initially thought that MMF would help in reducing/avoiding CNI-related nephrotoxicity. Elective avoidance of CNI in induction and maintenance MMF-based immunosuppression has resulted in an increased risk for acute and chronic rejection. A recent meta-analysis suggests that CNI elimination in patients on MMF with progressive renal dysfunction is associated with a better outcome, although more data are needed to support any recommendation. So far, the more conservative approach involving CNI minimization with MMF has been associated with amelioration of renal function and low risk for rejection, providing an adequate risk/benefit balance. However, MMF with belatacept might pave the way for CNI-free induction and maintenance immunosuppression. Meanwhile, the assessment of immunological risk by new monitoring tools could be a prerequisite to further implement such CNI sparing strategies.
Topics: Acute Disease; Calcineurin Inhibitors; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 19775321
DOI: 10.1111/j.1600-6143.2009.02812.x