Biologics in rheumatoid arthritis

2014 ◽  
Vol 1 (1) ◽  
pp. 34-37
Author(s):  
Khalid Testas ◽  
◽  
Samy Slimani ◽  
Lamia Djeghader ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
B Cells ◽  
Disease Activity ◽  
Small Molecule ◽  
Radiographic Progression ◽  
Tnf Alpha ◽  
Janus Kinases ◽  
Low Disease Activity ◽  
The World

Remission of low disease activity has become the main goal in the management of rheumatoid arthritis (RA), thanks to immunosuppressants but more importantly to a new emerging drug called biologics. Biologics used in RA have proved their efficacy on symptoms as well as radiographic progression, and they have been integrated into the recommendations for the management of RA. TNF alpha inhibitors with their five different molecules are the most prescribed bDMARDs in the world since their approval during the 1990s. Since then, more molecules were made available, targeting other compounds of the rheumatoid inflammation: IL1 (Anakinra), CD20 B cells (Rituximab), costimulation molecules of T cells (Abatacept), IL6 (Tocilizumab) and more recently small molecule inhibitors (Janus kinases), Tofacitinib.

Determining a Magnetic Resonance Imaging Inflammatory Activity Acceptable State Without Subsequent Radiographic Progression in Rheumatoid Arthritis: Results from a Followup MRI Study of 254 Patients in Clinical Remission or Low Disease Activity

2013 ◽  
Vol 41 (2) ◽  
pp. 398-406 ◽  
Author(s):  
Frédérique Gandjbakhch ◽  
Espen A. Haavardsholm ◽  
Philip G. Conaghan ◽  
Bo Ejbjerg ◽  
Violaine Foltz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Disease Activity ◽  
Clinical Remission ◽  
Radiographic Progression ◽  
Inflammatory Activity ◽  
Resonance Imaging ◽  
Low Disease Activity ◽  
Synovitis Score

Objective.To assess the predictive value of magnetic resonance imaging (MRI)-detected subclinical inflammation for subsequent radiographic progression in a longitudinal study of patients with rheumatoid arthritis (RA) in clinical remission or low disease activity (LDA), and to determine cutoffs for an MRI inflammatory activity acceptable state in RA in which radiographic progression rarely occurs.Methods.Patients with RA in clinical remission [28-joint Disease Activity Score-C-reactive protein (DAS28-CRP) < 2.6, n = 185] or LDA state (2.6 ≤ DAS28-CRP < 3.2, n = 69) with longitudinal MRI and radiographic data were included from 5 cohorts (4 international centers). MRI were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS). Statistical analyses included an underlying conditional logistic regression model stratified per cohort, with radiographic progression as dependent variable.Results.A total of 254 patients were included in the multivariate analyses. At baseline, synovitis was observed in 95% and osteitis in 49% of patients. Radiographic progression was observed in 60 patients (24%). RAMRIS synovitis was the only independent predictive factor in multivariate analysis. ROC analysis identified a cutoff value for baseline RAMRIS synovitis score of 5 (maximum possible score 21). Rheumatoid factor (RF) status yielded a significant interaction with synovitis (p value = 0.044). RF-positive patients with a RAMRIS synovitis score of > 5 vs ≤ 5, had an OR of 4.4 (95% CI 1.72–11.4) for radiographic progression.Conclusion.High MRI synovitis score predicts radiographic progression in patients in clinical remission/LDA. A cutoff point for determining an MRI inflammatory activity acceptable state based on the RAMRIS synovitis score was established. Incorporating MRI in future remission criteria should be considered.

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.

Optimal response to dimethyl fumarate associates in MS with a shift from an inflammatory to a tolerogenic blood cell profile

2017 ◽  
Vol 24 (10) ◽  
pp. 1317-1327 ◽  
Author(s):  
Silvia Medina ◽  
Noelia Villarrubia ◽  
Susana Sainz de la Maza ◽  
José Lifante ◽  
Lucienne Costa-Frossard ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Disease Activity ◽  
Cd8 T Cells ◽  
Blood Lymphocyte ◽  
Dimethyl Fumarate ◽  
Effector Memory ◽  
Tnf Alpha ◽  
Ifn Gamma ◽  
Optimal Response

Background: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. Objective: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. Methods: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up. Results: During treatment, all patients experienced an increase in the naive T cells and a decrease in effector memory ones. However, only NEDA patients showed a significant reduction in central memory CD4+ and CD8+ T cells, memory B cells, CD4+ T cells producing interferon (IFN)-gamma, CD8+ T cells producing tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma and B cells producing TNF-alpha. Additionally, they had an increase in regulatory CD56bright cells not observed in ODA group. After treatment, there was a negative correlation between CD56bright cells and CD8+ T cells producing IFN-gamma and TNF-alpha. Conclusion: A pro-tolerogenic shift in the blood leukocyte profile associates with an optimal response to DMF in MS.

Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis

2017 ◽  
Vol 77 (4) ◽  
pp. 515-522 ◽  
Author(s):  
Sophie Henaux ◽  
Adeline Ruyssen-Witrand ◽  
Alain Cantagrel ◽  
Thomas Barnetche ◽  
Bruno Fautrel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Initial Treatment ◽  
Radiographic Progression ◽  
Meta Analysis ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Systematic Analysis ◽  
Low Disease Activity ◽  
Increased Risk

ObjectivesTo assess the risk of losing remission, low disease activity (LDA) or radiographic progression in the case of (1) discontinuing or (2) tapering doses of biological disease-modifying antirheumatic drugs (bDMARDs) compared with continuation of the initial treatment regimen in rheumatoid arthritis (RA) patients with remission or LDA.Materials and methodsA systematic literature analysis was carried out through May 2017 on the PubMed, Embase, Cochrane and international congress databases, selecting controlled trials comparing bDMARDs discontinuation/tapering versus continuation in RA patients with remission or LDA. The meta-analysis assessed the risk ratio (RR) and 95% CI of losing remission or LDA and the risk of radiographic progression after (1) discontinuing and (2) tapering doses of bDMARDs versus continuing the initial treatment.ResultsThe meta-analysis comparing bDMARDs discontinuation versus continuation performed on nine trials showed an increased risk of losing remission (RR (95% CI)=1.97(1.43 to 2.73), P<0.0001) or LDA (RR (95% CI)=2.24(1.52 to 3.30), P<0.0001) and an increased risk of radiographic progression (RR (95% CI)=1.09(1.02 to 1.17), P=0.01) in case of bDMARD discontinuation. The meta-analysis comparing bDMARDs tapering versus continuation performed on 11 trials showed an increased risk of losing remission (RR (95% CI)=1.23(1.06 to 1.42), P=0.006) but no increased risk of losing LDA (RR (95% CI)=1.02 (0.85 to 1.23), P=0.81) nor any increased risk of radiographic progression (RR (95% CI)=1.09(0.94 to 1.26), P=0.26) in case of bDMARD tapering.ConclusionDiscontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographic progression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographic progression, even though there is an increased risk of losing remission.

scholarly journals Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Association with Worse Clinical Outcomes

2018 ◽  
Vol 45 (11) ◽  
pp. 1515-1521 ◽  
Author(s):  
Katie Bechman ◽  
Lieke Tweehuysen ◽  
Toby Garrood ◽  
David L. Scott ◽  
Andrew P. Cope ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Functional Disability ◽  
Radiographic Progression ◽  
Cox Regression ◽  
Short Form ◽  
Functional Health ◽  
Low Disease Activity ◽  
Sf 36

Objective.To investigate predictors of flare in rheumatoid arthritis (RA) patients with low disease activity (LDA) and to evaluate the effect of flare on 12-month clinical outcomes.Methods.Patients with RA who were taking disease-modifying antirheumatic drugs and had a stable 28-joint count Disease Activity Score (DAS28) < 3.2 were eligible for inclusion. At baseline and every 3 months, clinical (DAS28), functional [Health Assessment Questionnaire–Disability Index (HAQ-DI), EQ-5D, Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F), Medical Outcomes Study Short Form-36 (SF-36)], serum biomarkers [multibiomarker disease activity (MBDA) score, calprotectin, CXCL10], and imaging data were collected. Flare was defined as an increase in DAS28 compared with baseline of > 1.2, or > 0.6 if concurrent DAS28 ≥ 3.2. Cox regression analyses were used to identify baseline predictors of flare. Biomarkers were cross-sectionally correlated at time of flare. Linear regressions were performed to compare clinical outcomes after 1 year.Results.Of 152 patients, 46 (30%) experienced a flare. Functional disability at baseline was associated with flare: HAQ-DI had an unadjusted HR 1.82 (95% CI 1.20–2.72) and EQ-5D had HR 0.20 (95% CI 0.07–0.57). In multivariate analyses, only HAQ-DI remained a significant independent predictor of flare (HR 1.76, 95% CI 1.05–2.93). At time of flare, DAS28 and its components significantly correlated with MBDA and calprotectin, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers. Patients who flared had significantly worse outcomes at 12 months (HAQ-DI, EQ-5D, FACIT-F, SF-36, and radiographic progression).Conclusion.Flares occur frequently in RA patients with LDA and are associated with worse disease activity, quality of life, and radiographic progression. Higher baseline HAQ-DI was modestly predictive of flare, while biomarker correlation at the time of flare suggests a noninflammatory component in a majority of events.

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