- MeSH
- Pemphigoid, Benign Mucous Membrane * diagnostic imaging drug therapy pathology MeSH
- Cyclophosphamide administration & dosage MeSH
- Hyperemia drug therapy MeSH
- Drug Therapy, Combination MeSH
- Mycophenolic Acid administration & dosage MeSH
- Humans MeSH
- Conjunctival Diseases * diagnostic imaging drug therapy pathology MeSH
- Prednisolone administration & dosage MeSH
- Rituximab administration & dosage MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
Mycophenolate mofetil (MMF) is an immunosuppressant drug approved for prophylaxis of transplant rejection in patients undergoing solid organ transplantation and is further employed in management of various autoimmune disorders. MMF exhibits notable pharmacokinetic inter- and intraindividual variability necessitating tailored therapeutic approaches to achieve optimal therapeutic outcomes while mitigating risks of adverse effects. The objective of this review was to summarize factors that influence the pharmacokinetics of MMF and its active metabolite mycophenolic acid in order to deduce recommendations for personalized treatment strategies. Presumed predictors were analysed in relation to each of the four pharmacokinetic phases, providing tools and targets for MMF dosing optimization amenable to clinical implementation.
- MeSH
- Immunosuppressive Agents * pharmacokinetics administration & dosage MeSH
- Precision Medicine MeSH
- Mycophenolic Acid * pharmacokinetics administration & dosage MeSH
- Humans MeSH
- Graft Rejection prevention & control MeSH
- Organ Transplantation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Účinnost nintedanibu na zpomalení poklesu plicních funkcí u pacientů s progredujícím fibrotizujícím (PF) fenotypem intersticiálního plicního procesu (IPP) byla ověřena klinickou studií INBUILD, jejíž výsledky byly publikovány v roce 2019. Zatímco v této studii bylo souběžné použití nintedanibu a imunosupresiv omezeno, v klinické praxi před rozhodnutím, zda nintedanibem imunosupresi nahradit, nebo jej ke stávající léčbě přidat, stojíme poměrně často. Zatím nebylo publikováno mnoho prací zabývajících se snášenlivostí kombinované imunosupresivní a antifibrotické léčby. Sdělení přináší přehled zkušeností s kombinovanou imunosupresivní a antifibrotickou léčbou u šesti nemocných, s dobrou snášenlivostí léčby.
The effectiveness of nintedanib in slowing the decline in lung function in patients with a progressive fibrotic (PF) phenotype of the interstitial lung process (IPP) was validated in the INBUILD clinical trial, published in 2019. While the concomitant use of nintedanib and immunosuppressants was limited in this study, the practice before deciding whether to replace nintedanib with immunosuppression or to add it to existing treatment is quite common. To date, many studies have been published on the tolerability of combined immunosuppressive and antifibrotic therapy. The communication provides an overview of the experience with combined immunosuppressive and antifibrotic treatment in six patients with good tolerance.
- Keywords
- nintedanib, pirfenidon,
- MeSH
- Azathioprine administration & dosage MeSH
- Cyclophosphamide administration & dosage MeSH
- Adult MeSH
- Alveolitis, Extrinsic Allergic drug therapy MeSH
- Immunosuppression Therapy * methods adverse effects MeSH
- Protein Kinase Inhibitors * administration & dosage MeSH
- Lung Diseases, Interstitial diagnostic imaging drug therapy MeSH
- Drug Therapy, Combination MeSH
- Mycophenolic Acid administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug Substitution MeSH
- Connective Tissue Diseases diagnostic imaging drug therapy MeSH
- Occupational Diseases drug therapy MeSH
- Tomography, X-Ray Computed MeSH
- Prednisone administration & dosage MeSH
- Disease Progression MeSH
- Antineoplastic Agents administration & dosage adverse effects MeSH
- Waiting Lists MeSH
- Lung Transplantation MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Case Reports MeSH
BACKGROUND: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high-risk acute lymphoblastic leukemia (ALL) lacking a matched donor. METHODS: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in 2010-2020. RESULTS: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19-73) and 38 (18-75) years, respectively (p = .51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T-cell depletion (anti-thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p < .0001). Neutrophil (absolute neutrophil count >0.5 × 109 /L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81-2.62; p = .21) and HR = 0.81 (95% CI, 0.52-1.28, p = .38), respectively. HRs for leukemia-free survival, overall survival, and GVHD-free, relapse-free survival were respectively, HR = 1.05 (95% CI, 0.73-1.50, p = .8), HR = 1.17 (95% CI, 0.77-1.76, p = .46), and HR = 1.07 (95% CI, 0.78-1.46, p = .7) for haplo compared to MMUD. Acute (a)GVHD grade 2-4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08-2.76, p = .023), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups. CONCLUSION: Outcomes of MMUD and haplo transplants with PTCy-based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants.
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma * drug therapy MeSH
- Acute Disease MeSH
- Cyclophosphamide therapeutic use MeSH
- Adult MeSH
- HLA Antigens MeSH
- Mycophenolic Acid therapeutic use MeSH
- Humans MeSH
- Graft vs Host Disease * prevention & control MeSH
- Unrelated Donors MeSH
- Transplantation Conditioning adverse effects MeSH
- Retrospective Studies MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Biopsy methods MeSH
- Cyclophosphamide pharmacology therapeutic use MeSH
- Glucocorticoids pharmacology therapeutic use MeSH
- Hydroxychloroquine pharmacology therapeutic use MeSH
- Mycophenolic Acid pharmacology therapeutic use MeSH
- Humans MeSH
- Lupus Nephritis * diagnosis drug therapy MeSH
- Proteinuria diagnosis etiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered.
- MeSH
- COVID-19 prevention & control MeSH
- Mycophenolic Acid therapeutic use MeSH
- Humans MeSH
- Kidney Diseases * drug therapy immunology MeSH
- Antibodies, Viral MeSH
- Rituximab therapeutic use MeSH
- COVID-19 Vaccines * adverse effects immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The use of haploidentical hematopoietic cell transplantation (haplo-HCT) with peripheral blood stem cells (PBSCs) to treat acute myelogenous leukemia (AML) is increasing. We explored whether the addition of antithymocyte globulin (ATG) to post-transplantation cyclophosphamide (PTCy) allows better outcomes compared with PTCy alone in haplo-HCT with PBSCs (haplo-PBSCT). We included 441 adult patients undergoing a first haplo-PBSCT for AML in first or second complete remission; graft-versus-host disease (GVHD) prophylaxis contained either PTCy alone (n = 374) or ATG plus PTCy (n = 67), in addition to cyclosporine A (CsA) and mycophenolate mofetil (MMF) as other immunosuppressive agents. All transplantations were performed between 2011 and 2019. No major imbalances were observed between the 2 groups. For both groups, the median patient age was 56 years, and the median year of haplo-PBSCT was 2017. Most patients received a reduced-intensity conditioning regimen (57% in the PTCy group and 61% in the ATG+PTCy group; P = .54). The median follow-up was 19 months in the PTCy group versus 15 months in the ATG+PTCy group (P = .59), and the rate of neutrophil engraftment in the 2 groups was 97% and 98%, respectively. In univariate analysis, there were no statistical differences in transplantation outcomes between the 2 groups. In multivariate analysis, ATG+PTCy was associated with a lower risk of chronic GVHD compared with PTCy alone (hazard ratio, .46; 95% confidence interval, .23 to .93; P = .03). No between-group differences in the other transplantation outcomes were seen. In haplo-PBSCT, the addition of ATG to PTCy (with CsA and MMF) is feasible and better at preventing chronic GVHD and is associated with survival and transplantation outcomes comparable to those with PTCy alone, without increasing transplantation toxicity, mortality, or relapse incidence.
- MeSH
- Leukemia, Myeloid, Acute * MeSH
- Antilymphocyte Serum MeSH
- Cyclophosphamide MeSH
- Cyclosporine MeSH
- Transplantation, Haploidentical MeSH
- Bone Marrow MeSH
- Mycophenolic Acid MeSH
- Middle Aged MeSH
- Humans MeSH
- Graft vs Host Disease * MeSH
- Retrospective Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
Poly(ε-caprolactone; PCL) is an attractive biodegradable polymer that has been increasingly used to solve environmental problems caused by plastic wastes. In the present study, 468 bacterial isolates were recovered from soil samples and screened for PCL degradation activity. Of the isolates, 37 (7.9%) showed PCL depolymerase activity on PCL agar medium, with the highest activity being by isolate S22 which was identified using 16S rRNA and rpoB gene sequencing as Acinetobacter seifertii. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the degradation of PCL films after treatment with A. seifertii S22. The PCL depolymerase activity of A. seifertii S22 relied on the activity of esterase which occurred at an optimum temperature of 30-40 °C. The highest PCL depolymerase activity (35.5 ± 0.7 U/mL) was achieved after culturing A. seifertii S22 for 6 h in mineral salt medium (MSM) containing 0.1% Tween 20 and 0.02% ammonium sulfate as the carbon and nitrogen sources, respectively, which was approximately 20-fold higher than for cultivation in MSM supplemented with 0.1% PCL as sole carbon source. The results suggested that A. seifertii S22 or its enzymes could be used for PCL bioplastic degradation.
Intersticiální plicní postižení je častou orgánovou manifestací systémových chorob pojiva, jako jsou systémová sklerodermie, idiopatické zánětlivé myopatie či revmatoidní artritida. Byť tyto formy plicního postižení mají lepší prognózu než idiopatická plicní fibróza, představují i tak hlavní determinantu zvýšené morbidity a mortality revmatických chorob. V současnosti je třeba přehodnotit roli, která se připisuje metotrexátu v souvislosti s rozvojem intersticiálního plicního onemocnění. Z nově publikovaných studií vyplývá, že rozvoj intersticiálního plicního postižení není spojen s užíváním metotrexátu, ba naopak, jeho užívání může u nemocných rozvoj této manifestace pravděpodobně zpomalit. Historicky i v současnosti jsou manifestace intersticiálního plicního postižení u revmatických chorob léčeny především širokou paletou protizánětlivých léčiv, jejichž preference se u jednotlivých chorob liší. Je možné použít glukokortikoidy, cyklofosfamid, mykofenolát mofetil, azathioprin, kalcineurinové inhibitory či rituximab. Nová data poukazují také na efekt tocilizumabu v léčbě intersticiálního plicního postižení u sklerodermie. Efekt těchto léků je však nízký u fibrotizujících forem, kde se začínají uplatňovat antifibrotické léky používané již dříve v terapii idiopatické plicní fibrózy. Nintedanib je intracelulární inhibitor tyrozinkináz, který je již zavedenou léčebnou modalitou u idiopatické plicní fibrózy. Klinické studie prokázaly jeho efekt na zpomalení progrese intersticiálního plicního postižení u systémové sklerodermie, jakož i u dalších systémových chorob pojiva.
Interstitial lung disease is a common organ manifestation of systemic connective tissue diseases such as systemic scleroderma, idiopathic inflammatory myopathies or rheumatoid arthritis. Although these forms of pulmonary involvement have a better prognosis than idiopathic pulmonary fibrosis, they are still a significant determinant of increased morbidity and mortality in rheumatic diseases. The role of methotrexate in the development of interstitial lung disease needs to be reconsidered. Newly published studies show that the development of interstitial lung disease is not associated with its use; on the contrary, its use in patients is likely to slow down the development of this manifestation. Historically and today, the manifestations of interstitial lung disease in rheumatic diseases are treated primarily by a wide range of anti‐inflammatory drugs, whose preferences vary from disease to disease. Glucocorticoids, cyclophosphamide, mycophenolate mofetil, azathioprine, calcineurin inhibitors or rituximab may be used. The new data also point to the effect of tocilizumab in the treatment of interstitial lung disease in scleroderma. However, the effect of these drugs is low in fibrotic forms, where antifibrotic drugs used previously in the treatment of idiopathic pulmonary fibrosis are beginning to be used. Nintedanib is an intracellular tyrosine kinase inhibitor, an established treatment modality in idiopathic pulmonary fibrosis. Clinical studies have shown its effect in slowing disease progression in interstitial lung disease in systemic scleroderma as well as in other systemic connective tissue diseases.
- Keywords
- tocilizumab, nintedanib,
- MeSH
- Cyclophosphamide therapeutic use MeSH
- Glucocorticoids therapeutic use MeSH
- Interleukin-6 antagonists & inhibitors MeSH
- Lung Diseases, Interstitial * drug therapy MeSH
- Mycophenolic Acid therapeutic use MeSH
- Humans MeSH
- Methotrexate adverse effects MeSH
- Connective Tissue Diseases * complications MeSH
- Arthritis, Rheumatoid complications MeSH
- Rituximab therapeutic use MeSH
- Scleroderma, Systemic complications MeSH
- Protein-Tyrosine Kinases antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS: Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS: From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS: In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * drug therapy MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Remission Induction MeSH
- Mycophenolic Acid therapeutic use MeSH
- Humans MeSH
- Microscopic Polyangiitis * MeSH
- Peroxidase MeSH
- Antibodies, Antineutrophil Cytoplasmic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Systematic Review MeSH
