Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies.

To identify the targets recognized by anti-carbamylated protein antibodies (anti-CarP) in patients with early Rheumatoid Arthritis (RA), to study the cross-reactivity between anti-CarP and anti-citrullinated protein antibodies (ACPA) and to evaluate their prognostic value. 331 patients (184 RA and 147 other rheumatisms) from the Very Early Arthritis (VErA) French cohort were analyzed. We performed mass spectrometry analysis of RA sera displaying anti-CarP activity and epitope mapping of the carbamylated fibrinogen γ chain to identify immunodominant peptides.

Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis.

Background: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 ( and ), tyrosine kinase 2 (), signal transducer and activator of transcription 4 () and osteopontin (). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24).

Methods: Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response.

Soluble vascular endothelial (VE) cadherin and autoantibodies to VE-cadherin in rheumatoid arthritis patients treated with etanercept or adalimumab.

Objectives: The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate.

Methods: This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA.

Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data.

Introduction: Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX).

Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enrolled in the French Society of Rheumatology's ORA registry.

Objective: To study the effect of age on the risk-benefit balance of abatacept in RA.

Methods: Data from the French orencia and RA registry, including a 2-year follow-up, were used to compare the effectiveness and safety of abatacept according to age.

Results: Among the 1017 patients, 103 were very elderly (⩾75 years), 215 elderly (65-74), 406 intermediate aged (50-64) and 293 very young (<50).

Early phase clinical and biological markers associated with subclinical atherosclerosis measured at 7 years of evolution in an early inflammatory arthritis cohort.

Objectives: Accelerated atherosclerosis has emerged as a critical issue in rheumatoid arthritis (RA). There is a need to better understand the link between RA and atherosclerosis. Our aim was to identify parameters associated with the development of subclinical atheroma in a very early arthritis (VErA) cohort.

Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors.

Background: B and T cells play a key role in rheumatoid arthritis (RA) pathophysiology. RasGRP1 and RasGRP3 are involved in T and B cell receptors signaling, and belong to gene combination able to predict infliximab responsiveness, leading to the question of RasGRP1 and RasGRP3 involvement in RA.

Methods: RasGRP1 and RasGRP3 expression levels were measured by qRT-PCR and/or western-blot in peripheral blood mononuclear cells (PBMCs), in T and B cells from untreated RA patients and in RA patients treated by TNFα inhibitors.

Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response.

Objective: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects.

Improvement in patient-reported outcomes after rituximab in rheumatoid arthritis patients: An open-label assessment of 175 patients.

Objective: Patient-reported outcomes (PROs) reflect treatment efficacy from the patients' perspective. The objective was to assess PROs improvement with rituximab in rheumatoid arthritis.

Methods: Patients with long-standing rheumatoid arthritis received rituximab 1000mg twice at 2 weeks interval, and were assessed over 6 months.

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry.

Objectives: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry.

Methods: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA.

Switching from an anti-TNF monoclonal antibody to soluble TNF-receptor yields better results than vice versa: An observational retrospective study of 72 rheumatoid arthritis switchers.

Objectives: To evaluate the benefits for rheumatoid arthritis (RA) patients of switching from one tumor necrosis factor inhibitor (TNFi) to another based on reason for change (primary failure, escape or intolerance) and molecule-switching order.

Methods: Between 2000 and 2008, 356 RA patients prescribed a TNFi (infliximab [IFX], etanercept [ETA] or adalimumab [ADA]) and undergoing standardized evaluation were included in this retrospective study. Detailed demographic, clinical and biological data were collected before first biologic use and ≤6 months later to evaluate response based on EULAR-criteria.

Identification of S100A9 as biomarker of responsiveness to the methotrexate/etanercept combination in rheumatoid arthritis using a proteomic approach.

Objectives: One way to optimize the drug prescription in rheumatoid arthritis (RA) is to identify predictive biomarkers of drug responsiveness. Here, we investigated the potential "theranostic" value of proteins of the S100 family by monitoring levels of both S100A8 and S100A9 in blood samples from RA patients.

Design: For proteomic analysis, peripheral blood mononuclear cells (PBMC) and serum samples were collected in patients prior to initiation of the methotrexate/etanercept (MTX/ETA) combination.

Usefulness of monitoring of B cell depletion in rituximab-treated rheumatoid arthritis patients in order to predict clinical relapse: a prospective observational study.

Our objective was to evaluate the contribution of monitoring B cell subset depletion after rituximab in patients with rheumatoid arthritis (RA) in order to guide reintroduction to forestall relapse. This prospective, monocentre study included all RA patients receiving two 1-g rituximab infusions at a 15-day interval. The patients were followed clinically and biologically every 2 months until rituximab reintroduction.

Validation of the 2010-ACR/EULAR -classification criteria using newly EULAR-defined erosion for rheumatoid arthritis on the very early arthritis community-based (VErA) cohort.

Objective: To validate the 2010-ACR/EULAR criteria for rheumatoid arthritis (RA), taking into account the recent EULAR definition of "erosive disease", on the 310 patients comprising the very early arthritis cohort (VErA).

Methods: 2010-criteria performances were tested by first strictly applying its three items successively: ≥ 1 clinical synovitis/another disease(s)/score ≥ 6/10), then the typical erosion grid without obtaining a score of ≥ 6 to diagnose RA. We tested successively: no erosion (S1), ≥ 1 erosion(s) (S2), EULAR-defined erosive disease (S3).

Efficacy and safety of rituximab in elderly patients with rheumatoid arthritis enrolled in a French Society of Rheumatology registry.

Objective: The aim of this study was to compare the efficacy and safety of rituximab (RTX) as a function of patient age.

Methods: We included all rheumatoid arthritis patients in the AutoImmunity and Rituximab registry with a 2-year followup.

Results: Of the 1,709 patients, 191 were age ≥75 years, 417 were ages 65–74 years, 907 were ages 50–64 years, and 194 were age <50 years.

Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis.

Aims: This study aimed at describing adalimumab pharmacokinetics (PK) and the concentration-effect relationship of adalimumab using pharmacokinetic-pharmacodynamic (PK-PD) modelling in patients with rheumatoid arthritis (RA).

Methods: Adalimumab PK and PK-PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one-compartment model.

Influence of gender on response to rituximab in patients with rheumatoid arthritis: results from the Autoimmunity and Rituximab registry.

Objective: The response rate to many therapies for RA is lower in women. The aim of this study was to analyse the influence of gender on the response to rituximab (RTX) in patients with RA.

Methods: A total of 1709 RA patients were included in the French Autoimmunity and Rituximab (AIR) registry.

Use of whole-blood transcriptomic profiling to highlight several pathophysiologic pathways associated with response to rituximab in patients with rheumatoid arthritis: data from a randomized, controlled, open-label trial.

Objective: To identify a molecular signature that could be predictive of the clinical response to rituximab (RTX) and elucidate the transcriptomic changes after RTX therapy in patients with rheumatoid arthritis (RA), with the use of whole-blood transcriptomic profiling.

Methods: A microarray assay of the whole human genome was performed using RNA from peripheral blood samples obtained before the first cycle of RTX from 68 patients with RA in the SMART study. The transcriptomic profile was also assessed 24 weeks after the first administration of RTX (among 24 nonresponders and 44 responders, according to the European League Against Rheumatism response criteria at week 24).

Retention rates of adalimumab, etanercept and infliximab as first and second-line biotherapy in patients with rheumatoid arthritis in daily practice.

Objectives: To compare retention rates of adalimumab, etanercept and infliximab as first-line biotherapy in rheumatoid arthritis (RA), to determine causes of discontinuation, retention-associated factors, and retention rates of possible second-line TNF-α inhibitors (TNFi).

Methods: In this retrolective, multicentric study, medical charts of RA patients starting TNFi between March 2005 and April 2009 were reviewed, with follow-up between two and six years. The retention rate was estimated using the Kaplan-Meier method.

Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene.

Objective: To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid arthritis (RA) genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals.

Methods: We analysed a total of 11,715 RA cases and 26,493 controls from nine independent cohorts; all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on osteopontin (OPN) expression in macrophages and OPN serum levels was investigated.

Association of tobacco exposure and reduction of radiographic progression in early rheumatoid arthritis: results from a French multicenter cohort.

Objective: To investigate the initial response to treatment and risk of radiographic disease progression in current smokers (S), ex-smokers (EX), and nonsmokers (NS) in a prospective early arthritis cohort and to analyze the influence of smoking cessation on arthritis outcome.

Methods: The ESPOIR cohort is a prospective cohort study monitoring clinical, biologic, and radiographic data for patients with inflammatory arthritis lasting 6 weeks to 6 months. We examined the influence of smoking status on disease presentation (baseline characteristics) and therapeutic response at 1 year.

CCL19, a B cell chemokine, is related to the decrease of blood memory B cells and predicts the clinical response to rituximab in patients with rheumatoid arthritis.

Objective: Migration of B cells from peripheral blood to the synovium in patients with rheumatoid arthritis (RA) may predict clinical response to rituximab (RTX). We undertook this study to investigate whether serum levels of chemokines involved in B cell trafficking are correlated with blood levels of memory B cells or serum levels of B cell activation biomarkers before B cell depletion and whether chemokine levels predict RTX responsiveness.

Methods: Blood B cell subsets were analyzed by flow cytometry (CD27, IgD), and serum B cell activation biomarkers (rheumatoid factor, anti-cyclic citrullinated peptide, free light chains, IgG, IgA, IgM, and BAFF) were measured in 208 RA patients and 70 control subjects.

Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial.

Background: The licensed dose of rituximab in rheumatoid arthritis (RA) is two doses of 1000 mg given 2 weeks apart. A lower dose has never been specifically studied in patients with an inadequate response to anti-tumour necrosis factor (TNF) agents.

Objective: To compare the efficacy and safety of rituximab repeat treatment with two doses (1000 mg×1 and 1000 mg×2) following initial treatment with 1000 mg×2.