Methotrexate Triglutamate as a Determinant of Clinical Response in Mexican Patients with Rheumatoid Arthritis: Pharmacokinetics and dose Recommendation

2021 ◽  
Author(s):  
Ana P. Huerta‐García ◽  
Ana S. Rodríguez‐Báez ◽  
Susanna E. Medellín‐Garibay ◽  
Diana P. Portales‐Pérez ◽  
Marco U. Martínez‐Martínez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Dose Recommendation ◽  
Mexican Patients

scholarly journals AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1095.3-1096
Author(s):  
A. Karateev ◽  
A. Lila ◽  
E. Nasonov ◽  
V. Mazurov ◽  
D. Chakieva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Central Sensitization ◽  
Intracellular Signaling ◽  
Pain Reduction ◽  
Pain Severity ◽  
Jak Inhibitors ◽  
Significant Pain ◽  
Number Of Patients ◽  
Days Of Therapy

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р<0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared

scholarly journals AB0304 IMMUNOGENICITY OF BIOLOGIC DRUGS IN THE CLINICAL PRACTICE IN THE BULGARIAN POPULATION OF PATIENTS SUFFERING FROM RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1451.3-1451
Author(s):  
K. Kraev ◽  
M. Geneva-Popova ◽  
S. Popova
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Clinical Response ◽  
Neutralizing Antibodies ◽  
Tnf Alpha ◽  
Drug Bioavailability ◽  
Drug Induced ◽  
Etanercept Treatment ◽  
Markers Of Inflammation

Background:Biological drugs are protein derivatives that, as such, are highly immunogenic. In recent years there have been many conflicting opinions about the role of drug immunogenicity in clinical practice.Objectives:To evaluate the drug immunogenicity of TNF-alpha blocking drugs (etanercept and adalimumab) used to treat patients with rheumatoid arthritis. To determine whether their presence can alter the effect of treatment and to evaluate their role in the clinical practice of rheumatologists.Methods:121 patients with rheumatoid arthritis, as well as 31 healthy controls, similar in sex and age, were examined. They were all monitored at 0, 6, 12 and 24 months from the start of TNF-alpha blocker treatment. Demographics, vital signs, markers of inflammation such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity indices were examined at each visit, respectively. Drug-induced neutralizing antibodies, as well as drug bioavailability in patients treated with adalimumab, were examined by ELISA.Results:Drug-induced neutralizing antibodies to adalimumab were detected in 11.57% of patients at 6 month, in 17.64% of patients at 12 month, and 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not detected at 6 months, at 7.77% at 12 months, at 9.63% of patients at 24 months. Of the adalimumab patients who were having drug-induced antibodies, 92.59% had low drug bioavailability, while the remaining 7.41% of patients showed normal drug bioavailability despite the presence of drug-induced neutralizing antibodies. In terms of worsening of the disease activity, a positive correlation was found with the presence of drug antibodies - Pearson Correlation = 0.701, p = 0.001. Patients with poor clinical response and available drug antibodies receiving adalimumab were slightly more than those treated with etanercept at 12 and 24 months but the difference is non-significant-U = 0.527, p> 0.05 and U = 0.623, p> 0.05, respectively.Conclusion:Presence of drug-induced neutralizing antibodies in patients treated with adalimumab and etanercept has been associated with poor clinical response and worsening of the patient’s condition. Testing of drug-induced neutralizing antibodies as well as the drug bioavailability of the drug used can be used as reliable biomarkers in clinical rheumatology.References:[1]Benucci M., F.Li Gobbi, M. Meacii et al., “Antidrug antibodies against TNF-blocking agents: correlations between disese activity, hypersensitivity reactions, and different classes of immunoglobulins”, Biologics and Targets and Therapy, 2015: 9 7 -2.[2]Chen D., Y. Chen, W. Tsai et al., “ Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis”, Ann Rheum Dis. 2015 Mar; 74 (3).[3]Kalden J. and H. Schulze-Koops, “ Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment ”, Nature Reviews Rheumatology, 2017 volume 13, 707–718.[4]Wolf-Henning Boehnck, N. Brembilla, “ Immunogenicity of biological therapies: causes and consequences, ” Expert Review of Clinical Immunology, Vol 14, 2018, Issue 6, 513-523Disclosure of Interests:None declared

scholarly journals SAT0006 SIMULTANEOUS ANALYSIS OF ANTI-CCP, RHEUMATOID FACTOR, ANTI-PAD4 AND ANTI-CARBAMYLATED PROTEIN ANTIBODIES REVEALS INTERACTION EFFECTS WITH RESPONSE TO ANTI-TNF THERAPY IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 933.2-934
Author(s):  
A. Julià ◽  
M. Lopez Lasanta ◽  
F. Blanco ◽  
A. Gómez ◽  
I. Haro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Clinical Response ◽  
Therapeutic Approach ◽  
Drug Response ◽  
Single Marker Analysis ◽  
Das28 Score ◽  
Positive Interaction ◽  
Single Marker ◽  
Necrosis Factor

Background:Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal.Objectives:We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4).Methods:A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint.Results:Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044).Conclusion:The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships.Acknowledgments :We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gómez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Mª Luz García Vivar: None declared, Jordi Monfort: None declared, Simon Sánchez Fernandez: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-López: None declared, Raúl Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared

scholarly journals The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Martina Biggioggero ◽  
Federica Mesina ◽  
Ennio Giulio Favalli
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Tumor Necrosis ◽  
Retention Rate ◽  
First Line ◽  
Necrosis Factor Alpha ◽  
Comorbidity Index ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Moderate Response

Introduction. To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods. The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results. 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions. Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.

A8.08 The role of epigenetics in determining the clinical response to methotrexate for the treatment of rheumatoid arthritis

2016 ◽  
Vol 75 (Suppl 1) ◽  
pp. A67.3-A68
Author(s):  
S Cregan ◽  
K Creevey ◽  
T McGarry ◽  
C Orr ◽  
DJ Veale ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response

scholarly journals Is MRI a predictive biomarker for clinical response to biologics in rheumatoid arthritis?

2017 ◽  
Vol 76 (11) ◽  
pp. e45-e45 ◽  
Author(s):  
Joshua F Baker ◽  
Mikkel Østergaard ◽  
Philip G Conaghan
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Predictive Biomarker

scholarly journals Delay in imaging versus clinical response: A rationale for prolonged treatment with anti–tumor necrosis factor medication in early rheumatoid arthritis

2007 ◽  
Vol 57 (8) ◽  
pp. 1564-1567 ◽  
Author(s):  
Richard J. Wakefield ◽  
Jane E. Freeston ◽  
Elizabeth M. A. Hensor ◽  
Domini Bryer ◽  
Mark A. Quinn ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Clinical Response ◽  
Early Rheumatoid Arthritis ◽  
Tumor Necrosis ◽  
Prolonged Treatment ◽  
Necrosis Factor
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