scholarly journals JNK pathway‐associated phosphatase associates with rheumatoid arthritis risk, disease activity, and its longitudinal elevation relates to etanercept treatment response

2021 ◽  
Vol 35 (4) ◽  
Author(s):  
Li Sun ◽  
Jianxin Tu ◽  
Xiaowei Chen ◽  
Meijie Dai ◽  
Xiaoru Xia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Etanercept Treatment ◽  
Rheumatoid Arthritis Risk ◽  
Jnk Pathway

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 The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

2021 ◽  
Author(s):  
Yongji Li ◽  
Wendi Yang ◽  
Feng Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Treatment Efficacy ◽  
Th17 Cells ◽  
Immune Cell ◽  
Disease Risk ◽  
Th1 Cells ◽  
Clinical Role ◽  
Reactive Protein

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

PP001 Ultrasound To Guide Treatment Decisions In Rheumatoid Arthritis

2017 ◽  
Vol 33 (S1) ◽  
pp. 67-67
Author(s):  
E Simpson ◽  
Matt Stevenson ◽  
Emma Hock ◽  
Ruth Wong ◽  
R Wakefield ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Clinical Examination ◽  
Treatment Strategies ◽  
Cost Effective ◽  
Treatment Decisions ◽  
Potential Cost ◽  
Disease Modifying ◽  
Rheumatic Drug

INTRODUCTION:Ultrasound (US) detects synovitis more accurately than clinical examination (CE) in people with rheumatoid arthritis (RA). This review aimed to investigate the use of US, compared to CE alone, in treatment strategies for RA, and to estimate its potential to be cost-effective in making treatment decisions.METHODS:A systematic review was conducted of studies: investigating RA treatment response or strategies that compared US with CE-assessed synovitis; and of tapering RA treatment (1). A model was constructed to investigate the potential cost-effectiveness of US in (i) selecting patients suitable for treatment tapering; and (ii) avoiding treatment escalation (2).RESULTS:Seven prospective cohort studies suggested US-detected synovitis was significantly associated with a treatment response or tapering failure, whereas in most cases clinical examination alone was not. Two randomized controlled trials (RCTs) identified suggested that US added to the Disease Activity Index (DAS)-based treatment strategies but did not significantly improve primary outcomes, but was associated with improved rate of DAS remission. The evidence showed that some patients (proportions varied widely) who had achieved low disease activity could have treatment tapered, with no, or little, short-term harm to the patient.The model estimated that an average reduction of 2.5 percent in the costs of biological disease-modifying anti-rheumatic drug (bDMARDs) was sufficient to cover the costs of performing US every three months. This value increased to 4 percent and 13 percent for the costs of conventional disease-modifying anti-rheumatic drug (cDMARDs) depending on the assumed regimen.CONCLUSIONS:Use of US to monitor synovitis could potentially be a cost-effective approach, given that low proportions of patients for whom clinicians consider amending treatment, would need to taper treatment, or remain on therapy without escalation. US could provide clinicians with more confidence in reducing the drug burden. However, there is considerable uncertainty in this conclusion due to lack of robust data relating to key parameters.

Musculoskeletal ultrasound using superb microvascular imaging documents treatment response to biosimilar infliximab in rheumatoid arthritis

2021 ◽  
Vol 14 (2) ◽  
pp. e239112
Author(s):  
Julian Alejandro Santos ◽  
Cherica Afurong Tee ◽  
Romelito Jose Galvan Galsim ◽  
Michael Lucas Tee
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Activity Index ◽  
Power Doppler ◽  
Musculoskeletal Ultrasound ◽  
Joint Effusion ◽  
Das 28 ◽  
Superb Microvascular Imaging ◽  
Microvascular Imaging

A 60-year-old woman with rheumatoid arthritis consulted for acute flare. She had elevated disease activity score 28 - erythrocyte sedimentation rate (DAS 28-ESR) of 6.88 and clinical disease activity index (CDAI) of 32. Her 12-joint ultrasound revealed widespread joint effusion. Synovial vascularity scores measured through superb microvascular imaging (SMI) and power Doppler were universally increased. We documented her treatment response 2 weeks after she received a single dose of biosimilar infliximab using clinical and sonographic data. Her DAS 28-ESR and CDAI scores decreased to 4.21 and 7.0, respectively. Reduction in synovial vascularity scores was demonstrated using SMI. While there was near total resolution in joint effusion and tenosynovitis, SMI was able to demonstrate synovial vascularity in joints with no clinical swelling nor tenderness. Musculoskeletal ultrasound and superb microvascular imaging are useful adjuncts in evaluating synovitis in rheumatoid arthritis and documenting treatment response through documentation of synovial vascularity, effusion and tenosynovitis.

Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis

2017 ◽  
Vol 76 (12) ◽  
pp. 2031-2037 ◽  
Author(s):  
Maria Karolina Jonsson ◽  
Nina Paulshus Sundlisæter ◽  
Hilde Haugedal Nordal ◽  
Hilde Berner Hammer ◽  
Anna-Birgitte Aga ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Radiographic Progression ◽  
Activity Index ◽  
Inflammatory Marker ◽  
Target Therapy ◽  
Power Doppler ◽  
Treat To Target ◽  
Symptom Duration

ObjectivesCalprotectin is an inflammatory marker of interest in rheumatoid arthritis (RA). We evaluated whether the level of calprotectin was associated with disease activity, and if it was predictive of treatment response and radiographic progression in patients with early RA.MethodsPlasma from disease-modifying antirheumatic drug (DMARD)-naïve patients with RA fulfilling 2010 American College of Rheumatology/European League Against Rheumatism classification criteria with symptom duration <2 years was analysed for calprotectin at baseline, and after 1, 3 and 12 months. All patients received treat-to-target therapy, as part of a randomised controlled strategy trial (ARCTIC). The association between calprotectin, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and measures of disease activity were assessed by correlations. We used likelihood ratios and logistic regression models to assess the predictive value of the baseline inflammatory markers for treatment response and radiographic damage.Results215 patients were included: 61% female, 82% anti-citrullinated peptide antibody positive, mean (SD) age 50.9 (13.7) years and median (25, 75 percentile) symptom duration 5.8 (2.8, 10.5) months. Calprotectin was significantly correlated with Clinical Disease Activity Index (r=0.32), ESR (r=0.50) and ultrasonography power Doppler (r=0.42) before treatment onset. After 12 months of treatment, calprotectin, but not ESR and CRP, was significantly correlated with power Doppler (r=0.27). Baseline levels of calprotectin, ESR and CRP were not predictive of treatment response, but high levels of calprotectin were associated with radiographic progression in multivariate models.ConclusionsCalprotectin was correlated with inflammation assessed by ultrasound before and during DMARD treatment, and was also associated with radiographic progression. The data support that calprotectin may be of interest as an inflammatory marker when assessing disease activity in different stages of RA.Trial registration numberNCT01205854; Post-results.

scholarly journals Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients

2019 ◽  
Vol 78 (6) ◽  
pp. 761-772 ◽  
Author(s):  
Frances Humby ◽  
Myles Lewis ◽  
Nandhini Ramamoorthi ◽  
Jason A Hackney ◽  
Michael R Barnes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
B Cells ◽  
Disease Activity ◽  
Treatment Response ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Molecular Signatures ◽  
Early Ra ◽  
Treatment Naïve

ObjectivesTo unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.Methods144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.ResultsCellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) diffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.ConclusionsWe demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

Patients with Moderate Rheumatoid Arthritis (RA) Achieve Better Disease Activity States with Etanercept Treatment Than Patients with Severe RA

2009 ◽  
Vol 36 (3) ◽  
pp. 522-531 ◽  
Author(s):  
EDWARD KEYSTONE ◽  
BRUCE FREUNDLICH ◽  
MICHAEL SCHIFF ◽  
JUAN LI ◽  
MICHELE HOOPER
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Radiographic Progression ◽  
Severe Disease ◽  
High Dose ◽  
Etanercept Treatment ◽  
Low Disease Activity ◽  
Moderate Disease ◽  
Das28 Remission

Objective.This analysis examined clinical and radiographic responses to methotrexate (MTX), etanercept (ETN), and combination ETN and MTX in patients with moderate versus severe rheumatoid arthritis (RA) in both early and late disease.Methods.Data from the Trial of Etanercept and Methotrexate With Radiographic Patient Outcomes (TEMPO) and the Early Rheumatoid Arthritis trials were used. Patients were classified with moderate or severe RA based on Disease Activity Score including 28-joint count (DAS28). Outcomes included DAS28 remission, DAS28 low disease activity, Health Assessment Questionnaire (HAQ), American College of Rheumatology (ACR) scores, Total Sharp Score (TSS) progression, no radiographic progression (annualized change in TSS ≥ 0), change from baseline in TSS, and the change in TSS for patients who had radiographic progression (TSS > 0).Results.Patients with moderate disease generally achieved better clinical outcomes than patients with severe disease, including significant differences in DAS28 remission, low disease activity, and HAQ ≤0.5 at Month 12. Patients with baseline severe disease had higher ACR and DAS responses than patients with moderate disease.Conclusion.Patients with severe RA disease activity achieved substantial clinical improvement with high-dose MTX and/or ETN treatment, but patients with moderate disease were more likely to reach a lower disease activity state. These findings were independent of disease duration. The results support the opportunity for excellent clinical outcomes, particularly with combination therapy, in patients with moderate RA.

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