scholarly journals SAT0258 Weekly split dose compared with single dose oral methotrexate reduced polyglutamylation in red blood cells and increased the risk of adverse events in patients with rheumatoid arthritis

Author(s):  
Y. Yoshioka ◽  
K. Katayama ◽  
T. Kasama ◽  
M. Sato ◽  
S. Ohno ◽  
...  
2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Kyoko Honne ◽  
Takao Nagashima ◽  
Masahiro Iwamoto ◽  
Toyomi Kamesaki ◽  
Seiji Minota

A 57-year-old man with rheumatoid arthritis developed severe anemia during treatment with adalimumab plus methotrexate. Cold agglutinin disease was diagnosed because haptoglobin was undetectable, cold agglutinin was positive (1 : 2048), and the direct Coombs test was positive (only to complement). Although the cold agglutinin titer was normalized (1 : 64) after treatment with prednisolone (0.7 mg/kg/day for two weeks), the patient’s hemoglobin did not increase above 8 g/dL. When cold agglutinins were reexamined using red blood cells suspended in bovine serum albumin, the titer was still positive at 1 : 1024. Furthermore, the cold agglutinin had a wide thermal amplitude, since the titer was 1 : 16 at 30°C and 1 : 1 at 37°C. This suggested that the cold agglutinin would show pathogenicity even at body temperature. After the dose of prednisolone was increased to 1 mg/kg/day, the patient’s hemoglobin rapidly returned to the normal range. The thermal amplitude test using red blood cells suspended in bovine serum albumin is more sensitive than the standard test for detecting pathogenic cold agglutinins.


2016 ◽  
Vol 54 (1) ◽  
pp. 111-116 ◽  
Author(s):  
Hirokazu Kawase ◽  
Moritoki Egi ◽  
Tomoyuki Kanazawa ◽  
Kazuyoshi Shimizu ◽  
Yuichiro Toda ◽  
...  

1983 ◽  
Vol 12 (4) ◽  
pp. 333-347 ◽  
Author(s):  
Gerald D. Groff ◽  
Keith N. Shenberger ◽  
William S. Wilke ◽  
Thomas H. Taylor

2013 ◽  
Vol 5 ◽  
pp. 370-374
Author(s):  
Sylwia Elert-Kopeć ◽  
Małgorzata Tłustochowicz ◽  
Laura Załucka ◽  
Grzegorz Kopeć ◽  
Witold Tłustochowicz

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1164-1164
Author(s):  
M. Poudret ◽  
M. Norman ◽  
S. Hodin ◽  
A. S. Amouzougan ◽  
K. Boussoualim ◽  
...  

Background:Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA). Due to its short half-life, blood MTX dosage is not performed in current practice. Erythrocyte MTX-polyglutamate (MTX-PG), which penetrates into the red blood cells, would be correlated with the area under the MTX curve and would be more accessible for dosing. When treatment is initiated, its concentration correlates with efficacy and therapeutic adherence.Objectives:To determine the interest of erythrocyte MTX-PG dosage in case of failure of 1st line MTX treatment.Methods:In this single-centre cross-sectional study, RA patients presenting for consultation at the Saint-Etienne University Hospital, with a stable dose of MTX for more than 3 months at least 15 mg/week subcutaneously with either clinical remission (DAS28<2.6) or active disease (DAS28>3.2) were included between July 2nd 2018 and May 28th 2020. In order to assess therapeutic compliance, the patient completed the compliance questionnaire of Rheumatology (CQR) questionnaire. The determination of erythrocytic MTX-PG was performed on a 5 mL blood sample by liquid chromatography method for the determination of the different PG forms.Results:Sixty patients were included, 34 in the active RA group and 26 in the RA group in remission. One patient withdrew his consent. Only 16% of patients were observed with a CQR score > 80%. Patients in remission were leaner with a longer duration of disease and MTX treatment. The sex ratio, RA status, creatinine clearance and MTX dose was not different in both groups. The CQR was better in the remission group than in the active RA group. However, total MTX-PG was not different in the two groups. The same results were observed for the different forms of MTX-PG 1, 2, 3 or 4. In contrast, in the remission PR group, total MTX-PG or MTX-PG2, 3, 4 and 5 correlated inversely with BMI while MTX-PG3 correlated positively with BMI in the active PR group. In the active PR group, MTX-PG5 correlated with MTX dose.Conclusion:MTX-PG dosage is not a biomarker of good response to MTX in our study. However, compliance is a key factor to be considered in RA with active disease in adapting patient management.References:[1]Pasma A, Boer E den, Spijker A van ’t, Timman R, Bemt B van den, Busschbach JJV, et al. Nonadherence to disease modifying antirheumatic drugs in the first year after diagnosis: comparing three adherence measures in early arthritis patients. Rheumatology 2016;55:1812–1819.[2]Haandel L van, Becker ML, Leeder JS, Williams TD, Stobaugh JF. A novel high-performance liquid chromatography/mass spectrometry method for improved selective and sensitive measurement of methotrexate polyglutamation status in human red blood cells. Rapid Commun Mass Spectrom RCM 2009;23:3693–3702.[3]Dervieux T. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 2005;64:1180–1185.Disclosure of Interests:Marion POUDRET: None declared, Myriam Norman: None declared, Sophie Hodin: None declared, Adamah Stanislas AMOUZOUGAN: None declared, Karima BOUSSOUALIM: None declared, Astrid Coassy: None declared, Tiphany Neel: None declared, THIERRY THOMAS: None declared, Xavier DELAVENNE: None declared, Hubert MAROTTE Speakers bureau: Pfizer, Nordic, Paid instructor for: Amgen, Consultant of: Novartis, Grant/research support from: Nordic


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 465.2-465
Author(s):  
V. Sygyrta ◽  
G. Gridneva ◽  
A. Lila ◽  
E. Samarkina ◽  
N. Baymeeva ◽  
...  

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


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Amela Dervišević ◽  
Amila Muhić ◽  
Asija Začiragić ◽  
Almir Fajkić ◽  
Lejla Dervišević ◽  
...  

AbstractIntroduction: Present study was performed to verify red blood cell distribution width-to-platelet ratio (RPR) level in rheumatoid arthritis (RA) patients and to examine its correlation with clinical and biochemical indicators of disease activity status.Methods: In this cross-sectional analytical study, 67 patients with RA and 34 age- and gender-matched healthy control subjects were enrolled. Based on the disease activity score 28-ESR (DAS28-ESR), RA patients were divided into subgroups: low disease activity (n=20), moderate disease activity (n=22) and high disease activity (n=25). Laboratory tests included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, platelet count (PLT), red blood cells count (RBC), red blood cells distribution width (RDW) and fibrinogen concentration. Statistical analyses were carried out using SPSS 13 software. Statistical significance was set at a p-value less than 0.05.Results: There was statistically significant difference (p=0.006) between RPR in RA patients with different stages of disease activity, with higher values in patients with low disease activity. The RPR showed statistically significant negative correlations with ESR (rho= -0.309; p=0.012), CRP (rho= -0.421; p=0.001), swollen joint count - SJC (rho = -0.368; p=0.002) and tender joint count - TJC (rho= -0.355; p=0.003), DAS28-ESR (rho= -0.409; p=0.001), DAS28-CRP (rho= -0.422; p<0.0005) and Visual analogue scale - VAS (rho= -0.260; p=0.033) in RA patients.Conclusion: The present study provided evidence that the lower RPR values in RA patients are significantly associated with the disease activity indicators.


Sign in / Sign up

Export Citation Format

Share Document