scholarly journals Therapeutic drug monitoring of methotrexate and its metabolites in the red blood cells and mononuclear cells of patients with rheumatoid arthritis

2020 ◽  
Vol 14 (4) ◽  
pp. 60-64
Author(s):  
G. I. Gridneva ◽  
Yu. V. Muravyev ◽  
N. V. Baimeeva ◽  
V. S. Sygyrta ◽  
S. I. Glukhova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Drug Monitoring ◽  
Red Blood Cells ◽  
Drug Monitoring ◽  
Blood Cells ◽  
Older Patients ◽  
Time Course ◽  
Mononuclear Cells ◽  
Individual Characteristics ◽  
Therapeutic Drug

Objective: to assess the time course of changes in the concentration of methotrexate (MTX) and its main metabolites in the red blood cells (RBC) and mononuclear cells (MNC) of patients with rheumatoid arthritis (RA), by taking into account individual characteristics (age, statin therapy, and smoking).Patients and methods. The investigation enrolled 33 MTX-treated patients (mean age 53.2±11.7 years) with RA, who underwent therapeutic drug monitoring to measure the RBC and MNC concentrations of free MTX and MTX polyglutamates (MTXPGs) with 2, 3, and 4 glutamate residues (MTXPG 2–4) in using tandem chromatomass spectrometry after 4, 12, and 24 weeks of therapy.Results and discussion. Following 12 weeks, the concentration of MTXPG4 in the MNC was higher in patients taking statins, while that of MTX and MTXPG2 in the RBC were significantly lower than in smokers. At 24 weeks, older patients were observed to have a higher MTX level and a lower MTXPG4 concentration in the RBC.Conclusion. After 24 weeks of therapy, the RBC concentration of MTPG4 was lower and that of MTX was higher in older patients than in others, which confirms data on a slower MTX metabolism in the elderly. The use of statins is likely to have a positive impact on the accumulation of MTXPG. There is a statistically significantly lower RBC concentration of MTXPG in at 12 weeks of therapy.

Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Susanne Weber ◽  
Sara Tombelli ◽  
Ambra Giannetti ◽  
Cosimo Trono ◽  
Mark O’Connell ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Real Time ◽  
Drug Monitoring ◽  
Time Course ◽  
Drug Dosage ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Continuous Sampling ◽  
Real Time Analysis ◽  
Drug Concentrations

AbstractObjectivesTherapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).MethodsWe analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.ResultsUsing LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82).ConclusionsThe new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Rheumatoid Arthritis

2017 ◽  
Vol 39 (4) ◽  
pp. 364-369 ◽  
Author(s):  
Frédéric Medina ◽  
Chamaida Plasencia ◽  
Philippe Goupille ◽  
David Ternant ◽  
Alejandro Balsa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Current Practice ◽  
Therapeutic Drug

scholarly journals Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthritis?

2017 ◽  
Vol 83 (5) ◽  
pp. 962-975 ◽  
Author(s):  
Carla Bastida ◽  
Virginia Ruíz ◽  
Mariona Pascal ◽  
Jordi Yagüe ◽  
Raimon Sanmartí ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Biologic Agents ◽  
Therapeutic Drug

Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilars

2016 ◽  
Vol 75 (9) ◽  
pp. 1693-1696 ◽  
Author(s):  
M Begoña Ruiz-Argüello ◽  
Ainara Maguregui ◽  
Ainhoa Ruiz del Agua ◽  
Dora Pascual-Salcedo ◽  
Ana Martínez-Feito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Therapeutic Drug Monitoring ◽  
Rheumatic Diseases ◽  
Drug Monitoring ◽  
Correlation Coefficients ◽  
Therapeutic Drug ◽  
Switching Strategy ◽  
Loss Of Response ◽  
Rheumatic Patients

ObjectivesThe aim of this study was to determine whether antibodies to infliximab (IFX) in Remicade-treated patients cross-react with the biosimilar CT-P13.Methods250 consecutive patients with rheumatic diseases under Remicade and 77 controls were retrospectively selected for the study. Anti-IFX antibodies at drug through levels were measured in parallel with three different bridging ELISA assays: Promonitor-ANTI-IFX kit, which uses Remicade to detect antibodies, and two more assays that use either Inflectra or Remsima with the same format. Correlation and association between each assay was studied.Results50.4% of patients were tested positive with Promonitor-ANTI-IFX. All were antibodies to IFX (ATI)-positive when either Inflectra or Remsima assays were used. In all comparisons positive and negative percentage agreements were 100%, and correlation coefficients were ≥0.995. No differences between rheumatoid arthritis and spondyloarthritis, or between concomitant immunosuppressives, were observed.ConclusionsAnti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima. Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to IFX are also present in the biosimilar. Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.

scholarly journals POS0467 STUDY OF METHOTREXATE METABOLITES CONCENTRATIONS IN RED BLOOD CELLS AND MONONUCLEAR CELLS IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 465.2-465
Author(s):  
V. Sygyrta ◽  
G. Gridneva ◽  
A. Lila ◽  
E. Samarkina ◽  
N. Baymeeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Red Blood Cells ◽  
Correlation Coefficient ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Total Concentration ◽  
Pairwise Comparison ◽  
The Body ◽  
Inadequate Response ◽  
Mean Cell Volume

Background:Studying the dynamics of the methotrexate metabolites concentration in cells will help to predict the therapeutic effect and assess patient compliance. We suggest that studying the dynamics of changes in the concentration of methotrexate metabolites in mononuclear cells (MO) may be a more accurate method than measuring in red blood cells (RBC).Objectives:To study the dynamics of changes in the concentration of MTX and its metabolites in RBC and MO in methotrexate-naive patients with RA.Methods:33 patients (26 women, 7 men) aged 53.2 ± 11.7 years with a diagnosis of rheumatoid arthritis, according to the ACR / EULAR 2010 criteria, were included. All patients had GFR >60 ml/min. Patients were monitored after 4, 12, 24 and 36 weeks from the start of МТX. Mean Cell Volume (MCV) of RBC was measured by standard methods. Samples of RBC and MO were collected separately to determine the concentrations of MTX (basic monoglutamate form), total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), 7- hydroxymethotrexate (7-OH-MTX) by tandem mass spectrometry.Results:Table 1.Total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), nmol/lMe[25;75]MinMaxWeek 4RBC42.819.0;155.03987.7MO6.25.3;11.91.6147.2Week 12RBC48.117.1;89.00.1519.9MO10.93.9;31.00.9147.6Week 24RBC39.417.2;70.62.7191.8MO8.32.7;14.00.472.4A pairwise comparison of MTX, MTPG2-4 and 7-OH-MTX concentrations, according to the Wilcoxon method did not reveal statistically significant differences at weeks 4, 12 and 24. The concentration of the studied substances did not correlate with the value of the body mass index, taking statins, glucocorticoids, a cumulative dose of MTX, and the frequency of adverse reactions. At the week 4, of therapy, the level of MTPG4 in MO was inversely correlated with the duration of the disease (correlation coefficient - 0.58, p 0.05) The concentration of MTX and its metabolites in MO was lower in smokers (MTX 11.2 [2.6;21.9], 7-OH-MTX 2.1 [0.5; 10.4], MTPG2 0.5 [0.1;1.3]) than in non-smokers (MTX 46.5 [25.3;97.5], 7-OH-MTX 28.2 [7.1; 64.7], MTPG2 8.2 [4.1;32.9]), p = 0.02, 0.01 and 0.003, respectively. At week 24 of therapy, a negative correlation was found between age and MTPG4 level (correlation coefficient 0.51, p <0.05).Conclusion:The inadequate response to MT therapy in smokers, described in many previous studies, may be associated with a low concentration of the MTX metabolites in mononuclear cells.The level of MTPG4 in mononuclear cells increases more slowly in patients with a longer duration of the disease.Disclosure of Interests:None declared

scholarly journals Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonello Di Paolo ◽  
Giacomo Luci
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Personalized Medicine ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Individual Characteristics ◽  
Therapeutic Drug ◽  
Therapeutic Effects ◽  
Primary Resistance ◽  
Inflammatory Bowel

The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.

Therapeutic drug monitoring of biologicals in rheumatoid arthritis

2018 ◽  
Vol 30 (3) ◽  
pp. 266-275 ◽  
Author(s):  
Alfons A. den Broeder ◽  
Noortje van Herwaarden ◽  
Bart J.F. van den Bemt
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug
Sign in / Sign up

Export Citation Format

Share Document