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JAMA Dermatology Mar 2022
Topics: Autoimmune Diseases; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 35138336
DOI: 10.1001/jamadermatol.2021.5848 -
Transplant International : Official... Jun 2009The optimal maintenance therapy after lung transplantation remains to be established. The aim of this study was to analyse the impact of tacrolimus and mycophenolate...
The optimal maintenance therapy after lung transplantation remains to be established. The aim of this study was to analyse the impact of tacrolimus and mycophenolate mofetil (MMF) as first line immunosuppression on long-term survival and Bronchiolitis Obliterans Syndrome (BOS). From January 1996 through December 2006, all 155 recipients receiving tacrolimus and MMF as maintenance immunosuppression were included in this study. Tacrolimus and MMF was discontinued in 36 patients (23.2%). The overall survival rates were 91.6% at 6 months, 86.4% at 1 year, 74.9% at 3 years, 60.3% at 5 years and 32.4% at 10 years. The overall freedom from acute rejection was 74.6%, 63.2% and 59.4% at 1, 3, and 5 years respectively. The overall BOS-free survival was 95.6% at 1 year, 88.4% at 3 years, 69.5% at 5 years and 30.5% at 10 years. The development of BOS > or = 1 was associated with a significantly increased risk of death and reduced long-term survival. The combination of tacrolimus and MMF offers safe and reliable maintenance immunosuppression after lung transplantation. However, substantial improvements of long-term survival and freedom from BOS might only be achieved by a change in organ allocation policies and patient management beyond differential immunosuppressive protocols.
Topics: Bronchiolitis Obliterans; Female; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Mycophenolic Acid; Survival Analysis; Tacrolimus
PubMed: 19207186
DOI: 10.1111/j.1432-2277.2009.00843.x -
Journal of Veterinary Internal Medicine 2023Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive...
BACKGROUND
Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses.
HYPOTHESIS/OBJECTIVES
To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen.
ANIMALS
Six healthy Standardbred mares.
METHODS
Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability.
RESULTS
Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC ) of 12 594 h × ng/mL (8567-19 488 h × ng/mL) and terminal half-life (T ) of 11.3 hours (7.5-15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment.
CONCLUSION AND CLINICAL IMPORTANCE
Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.
Topics: Animals; Female; Horses; Mycophenolic Acid; Area Under Curve; Immunosuppressive Agents; Treatment Outcome
PubMed: 37469186
DOI: 10.1111/jvim.16797 -
British Journal of Clinical Pharmacology Apr 2017Elderly transplant recipients have a lower incidence of acute rejection, and a higher risk to die from infectious complications. A potential cause may be differences in...
AIMS
Elderly transplant recipients have a lower incidence of acute rejection, and a higher risk to die from infectious complications. A potential cause may be differences in the pharmacokinetics (PK) or pharmacodynamics (PD) of the immunosuppressive drugs they are taking. This study was designed to comprehensively evaluate the influence of age on the PK and PD of mycophenolic acid (MPA).
METHODS
In this study the PK and PD of MPA was studied in 26 elderly and 54 younger renal transplant recipients treated with mycophenolate mofetil and tacrolimus. Patients were sampled repetitively, both before and during the first 6 months after kidney transplantation. Age-related variability in MPA PK, baseline IMPDH activity, as well as MPA-induced IMPDH inhibition were studied.
RESULTS
The IMPDH activity pre-transplantation did not differ between elderly and younger patients. Neither IMPDH activity pre-transplantation nor maximum IMPDH inhibition was significantly correlated with the patients' age. The area under the MPA plasma concentration-time curve (AUC ) and the area under the effect (IMPDH activity)-time curve (AEC ) from 0 to 12 h were also not significantly different between the two groups. We found no significant differences in EC and E between elderly and younger patients.
CONCLUSIONS
Age did not significantly affect the PK or PD of MPA. It is unlikely that the lower incidence of acute rejection in elderly patients, or the higher risk to die from a severe infection in elderly patients is due to different handling of MPA in the elderly.
Topics: Adult; Age Factors; Aged; Area Under Curve; Female; Humans; IMP Dehydrogenase; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Time Factors; Transplant Recipients; Young Adult
PubMed: 27753146
DOI: 10.1111/bcp.13154 -
American Journal of Nephrology 2009Worldwide, IgA nephropathy (IgAN) is the most common type of glomerulonephritis. Mycophenolate mofetil (MMF) is relatively selective for lymphocytes and inhibits... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Worldwide, IgA nephropathy (IgAN) is the most common type of glomerulonephritis. Mycophenolate mofetil (MMF) is relatively selective for lymphocytes and inhibits antibody production by B cells more than other immunosuppressants. Several randomized controlled trials (RCTs) have analyzed the role of MMF in patients with IgAN. We conducted this meta-analysis of all available RCTs to ascertain the benefits and risks of MMF treatment in comparison with placebos or steroids in patients with IgAN.
METHODS
The studies were identified by extended computer-based searches of the PubMed database (April, 2008) and the Cochrane Library, without language restriction. References in Medline-cited studies were reviewed to identify additional reports not indexed by Medline. RCTs comparing treatment of IgAN with mycophenolate against placebo or steroids were included in the analysis.
RESULTS
We identified 32 potentially relevant articles, but only 4 RCTs, which had enrolled a total of 168 patients, were included. Our meta-analysis demonstrated that MMF treatment did not have statistically significant effects in reducing proteinuria or protecting renal function in patients with IgAN.
CONCLUSION
The currently available evidence does not support the routine use of MMF in patients with IgAN. Larger international collaborations should be put in place to further address this issue.
Topics: Creatinine; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Mycophenolic Acid; Proteinuria; Randomized Controlled Trials as Topic; Renal Replacement Therapy
PubMed: 18974636
DOI: 10.1159/000168483 -
Journal of Hepatology Sep 2011
Topics: Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid
PubMed: 21281682
DOI: 10.1016/j.jhep.2011.01.012 -
Experimental and Clinical... Aug 2020The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil... (Comparative Study)
Comparative Study
OBJECTIVES
The aim of this study was to evaluate recipient safety, tolerability, and pharmacokinetics of mycophenolate mofetil suspension compared with mycophenolate mofetil capsules as part of induction therapy after living-donor liver transplant.
MATERIALS AND METHODS
Between July 2017 and April 2019, we retrospectively enrolled 20 adult primary living-donor liver transplant recipients. Recipients were divided into 3 groups: group 1 received mycophenolate mofetil suspension of 3000 mg (n = 6), group 2 received 3000 mg mycophenolate mofetil via opened capsules (n = 8), and group 3 received mycophenolate mofetil suspension of 2000 mg (n = 6). Administration was started on postoperative day 1, with tacrolimus administered on postoperative day 2 or day 3.
RESULTS
The values of area under the plasma concentration time curve for 0 to 12 hours were significantly higher in the 3000 mg/day mycophenolate mofetil suspension group than in the 2000 mg/day mycophenolate mofetil suspension group (P = .024) and in the 3000mg/day mycophenolate mofetil capsule group (P = .013). Significant positive correlations were shown between blood concentration at 8 hours after administration and the plasma concentration time curve for 0 to 12 hours (r2 = 0.96; P < .001) in patients in the suspension group. No patients required mycophenolate mofetil reduction because of leukopenia and diarrhea. Only 1 biopsy-proven acute cellular rejection was recognized in the mycophenolate mofetil suspension group (at 2000 mg/day). There were no significant differences in frequency of opportunistic infections among the 3 groups.
CONCLUSIONS
Mycophenolate mofetil suspension is useful as part of immunosuppressive induction therapy after living-donor liver transplant because its concentration increases greater than that of mycophenolate mofetil capsules and because of the low risk of rejection and adverse events.
Topics: Aged; Capsules; Drug Compounding; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Pharmaceutical Solutions; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 32490763
DOI: 10.6002/ect.2020.0041 -
Scientific Reports Oct 2020Mycophenolate mofetil (MMF) is an immunosuppressive agent (IS) which is widely prescribed in neuromyelitis optica spectrum disorder (NMOSD) patients. We aim to assess... (Meta-Analysis)
Meta-Analysis
Mycophenolate mofetil (MMF) is an immunosuppressive agent (IS) which is widely prescribed in neuromyelitis optica spectrum disorder (NMOSD) patients. We aim to assess the efficacy and safety of MMF in controlling relapse and disease severity. Eligible studies obtained from the EMBASE and Ovid MEDLINE databases were studies of NMOSD patients treated with MMF, which reported treatment outcomes as Annualized Relapse Rate (ARR) or Expanded Disability Status Scale (EDSS) before and after treatment. Fifteen studies included 1047 patients, of whom 915 (87.4%) were aquaporin-4 immunoglobulin seropositive. The total number of patients that received MMF was 799. A meta-analysis on ARR was conducted in 200 patients from 4 studies and on EDSS in 158 patients from 3 studies. The result showed a significant improvement with a mean reduction of 1.13 [95% confidence interval (CI) 0.60-1.65] in ARR, and a mean reduction of 0.85 (95% CI 0.36-1.34) in EDSS after MMF therapy. Adverse events occurred in 106 (17.8%) of 594 patients during MMF therapy. This systematic review and meta-analysis showed that using MMF as a preventive therapy in NMOSD patients can significantly reduce relapse rates and improve disease severity with acceptable tolerability.
Topics: Humans; Immunosuppressive Agents; Mycophenolic Acid; Neuromyelitis Optica; Treatment Outcome
PubMed: 33028926
DOI: 10.1038/s41598-020-73882-8 -
Frontiers in Immunology 2022Regulators of TLRs signaling pathways play an important role in the control of the pro-inflammatory response that contributes to sepsis-induced tissue injury....
Regulators of TLRs signaling pathways play an important role in the control of the pro-inflammatory response that contributes to sepsis-induced tissue injury. Mycophenolate mofetil, an immunosuppressive drug inhibiting lymphocyte proliferation, has been reported to be a regulator of TLRs signaling pathways. Whether MMF used at infra-immunosuppressive doses has an impact on survival and on innate immune response in sepsis is unknown. C57BL/6J mice were infected intraperitoneally with 10 CFU , and treated or not with low-dose of MMF (20mg/kg/day during 4 days). Survival rate and bacterial clearance were compared. Cytokine levels, quantitative and qualitative cellular responses were assessed. - infected mice treated with MMF exhibited improved survival compared to non-treated ones (48% vs 10%, p<0.001). With the dose used for all experiments, MMF did not show any effect on lymphocyte proliferation. MMF treatment also improved local and systemic bacterial clearance, improved phagocytosis activity of peritoneal macrophages resulting in decreased inflammatory cytokines secretion. MMF-treated mice showed enhanced activation of NF-κB seemed with a suspected TLR4-dependent mechanism. These results suggest that infra-immunosuppressive doses of MMF improve host defense during sepsis and protects infected mice from fatal outcome by regulating innate immune responses. The signaling pathways involved could be TLR4-dependent. This work brings new perspectives in pathogenesis and therapeutic approaches of severe infections.
Topics: Animals; Bacteremia; Cytokines; Disease Models, Animal; Immunosuppressive Agents; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mycophenolic Acid; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Toll-Like Receptor 4
PubMed: 35936013
DOI: 10.3389/fimmu.2022.939213 -
BMC Cancer Mar 2020Clinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a...
Phase II, multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Mycophenolate Mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): rationale and design of the ESMMO trial.
BACKGROUND
Clinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a substantial need for further research and development to identify and develop more efficacious agents/regimens in order to improve clinical outcomes of patients for whom the prognosis is unfavorable. Recently, mycophenolate mofetil, a prodrug of mycophenolic acid, has been found to have anticancer activity against osteosarcoma in both in vitro and animal experiments, so that further investigation in humans is warranted.
METHODS
A total of 27 patients with high-grade locally advanced or metastatic osteosarcoma will be enrolled into this phase II, multi-center, open-label, single-arm, two-stage clinical trial. The main objectives of this study are to determine the efficacy and safety of mycophenolate mofetil in the patients. The primary endpoint is progression-free survival at 16 weeks; the secondary endpoints include progression-free survival, overall survival, overall response rate, safety parameters, pharmacokinetic parameters, biomarkers, pain score, and quality of life. Mycophenolate mofetil at the initial dose of 5 g/day or lower will be administered for 4 cycles (28 days/cycle) or until disease progression or unacceptable toxicity. The dose of mycophenolate mofetil may be reduced by 1-2 g/day or withheld for some Grade 3 or Grade 4 toxicities whenever clinically needed. The duration of study participation is approximately 4-5 months, with a minimum of 12 study visits. If mycophenolate mofetil proves beneficial to some patients, as evidenced by stable disease or partial response at 16 weeks, administration of mycophenolate mofetil will continue in the extension period.
DISCUSSION
This trial is the first step in the translation of therapeutic potential of mycophenolate mofetil emerging from in vitro and animal studies into the clinical domain. It is designed to assess the efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma. The results will provide important information about whether or not mycophenolate mofetil is worth further development.
TRIAL REGISTRATION
This trial was prospectively registered on Thai Clinical Trials Registry (registration number: TCTR20190701001). The posted information will be updated as needed to reflect protocol amendments and study progress.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Humans; Mycophenolic Acid; Neoplasm Staging; Osteosarcoma; Quality of Life; Survival Analysis; Treatment Outcome
PubMed: 32228535
DOI: 10.1186/s12885-020-06751-2