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Rheumatology (Oxford, England) Mar 2021To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma.
OBJECTIVES
To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma.
METHODS
Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis.
RESULTS
MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy.
CONCLUSION
The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment.
Topics: Antirheumatic Agents; Child; Female; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Methotrexate; Mycophenolic Acid; Retrospective Studies; Scleroderma, Localized; Thermography; Treatment Failure; Treatment Outcome
PubMed: 32978631
DOI: 10.1093/rheumatology/keaa392 -
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 -
Molecules (Basel, Switzerland) Aug 2023Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine... (Review)
Review
Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10-50 µL) within a few seconds (2-4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS). After optimization and validation of an analytical method of a drug taken by VAMS, a clinical validation study is needed to show that the results by VAMS can substitute what is gained from CVS and to justify implementation in routine practice. This narrative review aimed to assess and present studies about optimization and analytical validation of assays for drugs taken by VAMS, considering their physicochemical drug properties, extraction conditions, validation results, and studies on clinical validation of VAMS compared to CVS. The review revealed that the bio-analysis of many drugs taken with the VAMS technique was optimized and validated. However, only a few clinical validation studies have been performed so far. All drugs that underwent a clinical validation study demonstrated good agreement between the two techniques (VAMS and CVS), but only by Bland-Altman analysis. Only for tacrolimus and mycophenolic acid were three measurements of agreement evaluated. Therefore, VAMS can be considered an alternative to CVS in routine practice, especially for tacrolimus and mycophenolic acid. Still, more extensive clinical validation studies need to be performed for other drugs.
Topics: Mycophenolic Acid; Tacrolimus; Biological Assay
PubMed: 37630297
DOI: 10.3390/molecules28166046 -
Frontiers in Immunology 2022Belatacept (Bela) was developed to reduce nephrotoxicity and cardiovascular risk that are associated with the chronic use of Calcineurin inhibitors (CNIs) in kidney... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Belatacept (Bela) was developed to reduce nephrotoxicity and cardiovascular risk that are associated with the chronic use of Calcineurin inhibitors (CNIs) in kidney transplant recipients. The use of Bela with early steroid withdrawal (ESW) and simultaneous CNI avoidance has not been formally evaluated.
METHODS
At 3 months post-transplant, stable kidney transplant recipients with ESW on Tacrolimus (Tac) + mycophenolate (MPA) were randomized 1:1:1 to: 1) Bela+MPA, 2) Bela+low-dose Tac (trough goal <5 ng/mL), or 3) continue Tac+MPA. All patients underwent surveillance graft biopsies at enrollment and then at 12, and 24 months post-transplant. Twenty-seven recipients were included; 9 underwent conversion to Bela+MPA, 8 to Bela+low-dose Tac and 10 continued Tac+MPA. Serial blood samples were collected for immune phenotyping and gene expression analyses.
RESULTS
The Bela+MPA arm was closed early due to high rate of biopsy proven acute rejection (BPAR). The incidence of BPAR was 4/9 in Bela+MPA, 0/8 in Bela+low dose Tac and 2/10 in Tac+MPA, P= 0.087. The Bela+low-dose Tac regimen was associated with +8.8 mL/min/1.73 m increase in eGFR compared to -0.38 mL/min/1.73 m in Tac+MPA, P= 0.243. One graft loss occurred in the Bela+MPA group. Immunophenotyping of peripheral blood monocyte count (PBMC) showed that CD28CD4 and CD28CD8 T cells were higher in Bela+MPA patients with acute rejection compared to patients without rejection, although the difference did not reach statistical significance.
CONCLUSIONS
Our data indicate that, in steroid free regimens, low-dose Tac maintenance is needed to prevent rejection when patients are converted to Bela, at least when the maneuver is done early after transplant.
Topics: Humans; Abatacept; Calcineurin; Calcineurin Inhibitors; CD28 Antigens; CD8-Positive T-Lymphocytes; Immunosuppressive Agents; Kidney Transplantation; Leukocytes, Mononuclear; Mycophenolic Acid; Steroids; Tacrolimus; Drug Substitution
PubMed: 36601111
DOI: 10.3389/fimmu.2022.1096881 -
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 -
Journal of Hazardous Materials Apr 2023The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and...
The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and the temporal evolution of cytostatics in wastewaters from a Portuguese hospital center was evaluated through a 9-month sampling campaign, comprising a total of one hundred and twenty-nine samples, collected from May 2019 to February 2020. Eleven cytostatics out of thirteen pharmaceuticals were studied, including flutamide, mycophenolate mofetil and mycophenolic acid, which have never been monitored before. Target analytes were extracted and quantified by solid-phase extraction coupled to liquid-chromatography-tandem mass spectrometry analysis; the method was fully validated. All pharmaceuticals were detected in at least one sample, bicalutamide being the one found with higher frequency (detected in all samples), followed by mycophenolic acid, which was also the compound detected at higher concentrations (up to 5340 ± 211 ng/L). Etoposide, classified as carcinogenic to humans, was detected in 60% of the samples at concentrations up to 142 ± 15 ng/L. The risk from exposure to cytostatics was estimated for aquatic organisms living in receiving bodies. Cyclophosphamide, doxorubicin, etoposide, flutamide, megestrol and mycophenolic acid are suspected to induce risk. Long-term and synergic effects should not be neglected, even for the cytostatics for which no risk was estimated.
Topics: Humans; Cytostatic Agents; Flutamide; Etoposide; Mycophenolic Acid; Water Pollutants, Chemical; Solid Phase Extraction; Environmental Monitoring; Pharmaceutical Preparations
PubMed: 36731320
DOI: 10.1016/j.jhazmat.2023.130883 -
Archives of Pathology & Laboratory... Sep 2019Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver... (Review)
Review
CONTEXT.—
Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver complications.
OBJECTIVE.—
To detail the pathologic features of the various gastrointestinal and liver complications occurring after hematopoietic stem cell transplantation in relation to their clinical context. The specific complications covered include graft-versus-host disease, mycophenolate mofetil-induced injury, timeline of infections, neutropenic enterocolitis, gastrointestinal thrombotic microangiopathy, sinusoidal obstruction syndrome, hepatic iron overload, and the controversy around cord colitis syndrome.
DATA SOURCES.—
The content of this article is based on pertinent peer-reviewed articles in PubMed, relevant textbooks, and on the authors' personal experiences.
CONCLUSIONS.—
The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.
Topics: Biopsy; Colitis; Enterocolitis, Neutropenic; Gastrointestinal Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Infections; Liver Diseases; Mucous Membrane; Mycophenolic Acid; Thrombotic Microangiopathies
PubMed: 30838881
DOI: 10.5858/arpa.2018-0282-RA -
ACS Applied Bio Materials Oct 2023Exosomes are natural endogenous extracellular vesicles with phospholipid-based bilayer membrane structures. Due to their unique protein-decorated membrane properties,...
Exosomes are natural endogenous extracellular vesicles with phospholipid-based bilayer membrane structures. Due to their unique protein-decorated membrane properties, exosomes have been regarded as promising drug carriers to deliver small molecules and genes. A number of approaches have been developed for exosome-based drug loading. However, the drug loading capability of exosomes is inconsistent, and the effects of loading methods on the therapeutic efficacy have not been investigated in detail. Herein, we developed anti-inflammatory drug-loaded exosomes as an immunomodulatory nanoplatform. Naïve macrophage-derived exosomes (Mϕ-EVs) were loaded with the anti-inflammatory drug mycophenolic acid (MPA) by three major loading methods. Loading into exosomes significantly enhanced anti-inflammatory and antioxidation effects of MPA in vitro compared to free drugs. These findings provide a scientific basis for developing naïve macrophage-secreted exosomes as drug carriers for immunotherapy.
Topics: Mycophenolic Acid; Myoblasts, Cardiac; Extracellular Vesicles; Drug Carriers; Macrophages; Anti-Inflammatory Agents
PubMed: 37774367
DOI: 10.1021/acsabm.3c00475 -
Clinical Journal of the American... Mar 2022
Topics: Cyclosporine; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Mycophenolic Acid
PubMed: 35121594
DOI: 10.2215/CJN.00690122 -
The Journal of Biological Chemistry Oct 2022Adipocyte browning is one of the potential strategies for the prevention of obesity-related metabolic syndromes, but it is a complex process. Although previous studies...
Adipocyte browning is one of the potential strategies for the prevention of obesity-related metabolic syndromes, but it is a complex process. Although previous studies make it increasingly clear that several transcription factors and enzymes are essential to induce browning, it is unclear what dynamic and metabolic changes occur in induction of browning. Here, we analyzed the effect of a beta-adrenergic receptor agonist (CL316243, accelerator of browning) on metabolic change in mice adipose tissue and plasma using metabolome analysis and speculated that browning is regulated partly by inosine 5'-monophosphate (IMP) metabolism. To test this hypothesis, we investigated whether Ucp-1, a functional marker of browning, mRNA expression is influenced by IMP metabolism using immortalized adipocytes. Our study showed that mycophenolic acid, an IMP dehydrogenase inhibitor, increases the mRNA expression of Ucp-1 in immortalized adipocytes. Furthermore, we performed a single administration of mycophenolate mofetil, a prodrug of mycophenolic acid, to mice and demonstrated that mycophenolate mofetil induces adipocyte browning and miniaturization of adipocyte size, leading to adipose tissue weight loss. These findings showed that IMP metabolism has a significant effect on adipocyte browning, suggesting that the regulator of IMP metabolism has the potential to prevent obesity.
Topics: Animals; Mice; Adipocytes; Adipose Tissue, Brown; Adipose Tissue, White; Inosine Monophosphate; Metabolomics; Mice, Inbred C57BL; Mycophenolic Acid; Obesity; RNA, Messenger
PubMed: 36063990
DOI: 10.1016/j.jbc.2022.102456