French Rheumatoid Arthritis Patients Research Articles

Two-year treatment persistence with subcutaneous abatacept in rheumatoid arthritis: results from the French cohort of the ASCORE study.

While multiple studies have investigated treatment persistence rates with intravenous abatacept, limited information is available about real-world treatment continuation with the subcutaneous form. The international ASCORE study described the characteristics and treatment persistence of real-world patients with rheumatoid arthritis (RA) receiving subcutaneous abatacept. This article presents the findings of the French cohort. This was an observational study in French RA patients who initiated subcutaneous abatacept between August 2014 and January 2017. The primary endpoint was treatment maintenance at 2 years, analysed according to the number of previous biologic therapies. Of 546 evaluable patients, 281 (51.5%) were biologic-naive, 265 (48.5%) had experienced failure with 1 (n=134; 24.5%) or ≥2 (n=131; 24.0%) biologic therapies. At enrolment, patients who had experienced failure with ≥1 biologic therapy had more erosions and a longer duration of RA compared with biologic-naive patients, but had comparable mean disease activity scores. Overall, 43.0% of patients (95% confidence interval 38.6-47.2) were still taking subcutaneous abatacept at 2 years, which was comparable with that in other countries participating in ASCORE. The abatacept persistence rate was higher in biologic-naive patients (48.8%) than in those with 1 (40.9%) or ≥2 (32.8%) biologic therapy failures. The main reason for discontinuing abatacept was lack of efficacy (46.6%). In current practice in France, the rate of subcutaneous abatacept persistence at 2 years was comparable with that of the intravenous form. Treatment persistence was higher when abatacept was used as first-line versus later-line biologic therapy.

Joint Destruction Is Associated With All Types of Cardiovascular Events in French Rheumatoid Patients: A Real-Life Study With Very Long Follow-Up.

Objective: Rheumatoid arthritis (RA) leads not only to joint destruction but also to systemic manifestations, with an increased incidence of cardiovascular events (CVE). Many studies have shown a link between RA severity and CV risk, but the duration of follow-up remains often insufficient to allow a conclusion. The CVE definition was generally reduced to myocardial infarction and stroke, and few studies were conducted in non-Anglo-Saxon countries with low CV incidence. This study aimed to assess the relationship between joint destruction and the occurrence of different types of CVE in a large cohort of French RA patients with a long-term follow-up.Methods: This historical cohort study included 571 RA patients followed between 1992 and 2012 in Lyon, France. The primary endpoint was the first occurrence of a CVE. Logistic regressions were used to identify factors associated with CVE occurrence. Cox proportional hazard models were performed as a separate analysis to take advantage of the long-term follow-up.Results: During a mean follow-up of 16.1 years, 30.3% of patients experienced a CVE, mostly acute arterial events. Joint destruction was associated with an increased risk of CVE [odds ratio = 3.72; 95% confidence interval (CI), 1.09–15.35; p = 0.047] among non-smoker RA patients. A survival analysis revealed that joint destruction was associated with a shorter time to onset of the first CVE only among non-smokers (hazard ratio = 3.44; 95% CI, 1.07–11.04; p = 0.038).Conclusion: Joint destruction is associated with CVE occurrence in RA patients from a population with a lower incidence of CV disease. This study suggests that RA patients, especially those with destruction, merit the institution of precise guidelines to manage this CV risk, and trials are required to evaluate them.

SAT0064 VACCINATION RATE AND RISK FACTORS FOR NON-VACCINATION IN RHEUMATOID ARTHRITIS: A CROSS-SECTIONAL PROSPECTIVE MULTICENTRIC OBSERVATIONAL STUDY

Background:Rheumatoid arthritis (RA) patients are at increased risk of infections, some of which could be prevented in part by vaccination (1). Influenza and pneumococcal vaccines are recommended in RA (2). However, vaccination coverage of these patients remains very low. Five years ago, we found in a previous study that vaccination rates in France were 55% for pneumococcal and 60% for influenza vaccines (3).Objectives:The aim of our study was to evaluate the vaccination rate among RA patients, compare it with our previous results, and identify factors associated with non-vaccination.Methods:We conducted a cross sectional multicentric observational study in the rheumatology departments of 5 university hospitals in France. Data were collected from December 2018 to July 2019. Outpatients and hospitalized adult patients with RA according to the ACR/EULAR 2010 criteria were included. Data were collected during a single visit through an anonymous questionnaire completed by the patients. Pearson Chi-squared analysis and multivariable logistic regression were used to compare characteristics of vaccinated versus non vaccinated patients.Results:584 patients (77.9% of women, mean age 61.8±12.6 years old) were included. 81.7% were RF and/or ACPA positive, with a mean RA duration of 15.7±10.5 years, 58.2% were treated with methotrexate (MTX), and 68.6% with a biologic. Vaccination rate against pneumococcal was 78.9% (versus 55% in 2013, p<0.0001) and 60.4% for influenza (versus 60% in 2013). The main reason for non-vaccination was absence of vaccine proposal (59.2%) for pneumococcal, and fear of vaccines (56.7%) for influenza. In the multivariate analysis, a higher level of education (OR [CI95] 4.4 [2.3-8.4], p<0.0001), a very good opinion on vaccination (2.1 [1.1-4.1], p=0.003), vaccination against influenza done (2.3 {1.3-4.2], p=0.006), and exposure to biologics (4.0 [2.2-7.4], p<0.0001) were associated with vaccination against pneumococcal. Age over 65 years old (2.0 [1.2-3.2], p=0.006), participation in a patients’ association (3.6 [1.4-8.9], p=0.006), vaccination against pneumococcal done (2.4 [1.3-4.5], p=0.004), exposure to biologics (2.1 [1.2-3.7], p=0.006), a good (3.3 [1.4-8.9], p=0.03) and a very good opinion on vaccination (6.6 [2.8-15.6], p<0.0001) were associated with vaccination against influenza.Conclusion:Vaccination rate against pneumococcal increased over the last 5 years but remained stable for influenza vaccine in French RA patients. This could be improved with patient’s information and education, especially in patients age under 65, biologic naïve and with a bad opinion about vaccination.

A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients.

Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested.

FRI0182 Non-biologics disease modifying anti-rheumatic drugs (nbdmards) and biologics agents acquisition and adherence among french rheumatoid arthritis patients in real life population: results from a cross-sectional study

BackgroundRecent meta-analysis established that the efficacy of combination therapy with a biological agent is superior to methotrexate for remission (1). Moreover, superiority of combination of anti-TNFa (aTNF) + nbDMARDs over...

A Functional Haplotype of PADI4 Gene in Rheumatoid Arthritis: Positive Correlation in a French Population

A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies. DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using an ELISA technique. We focused on PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PADI4_89*G PADI4_90*T), described, respectively, as "nonsusceptible" and "susceptible." A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13%; p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes. Our findings confirm those of Japanese, Korean, and Canadian studies and suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations.

Impact of etanercept on the costs of rheumatoid arthritis (RA): Results from a French observational study

Introduction Economical impact of rheumatoid arthritis (RA) has been widely modified thanks to TNF inhibitors. Our study aims to estimate the impact etanercept prescription, in term of health resources consumption, within a regional cohort of French RA patients. Methods The study included 148 RA patients, with a mean follow-up duration of 343 days before and after etanercept initiation. Data were anonymously collected from ERASME database of French Health Insurance in Midi-Pyrénées region. A patient-by-patient microcosting approach was performed. Results The average annual cost per patient, attributable to RA, was 2.8 times higher after treatment by etanercept than before (15,148.57€ versus 5248.95€). We observed a rise in pharmaceutical costs, from 11.7% of direct medical costs before to 69.7% after etanercept initiation (120.12€ versus 9995.23€). We observed a small decrease particularly for NSAIDs (142.14€ versus 102.21€) and physiotherapy (286.40€ versus 138.77€). Attributable act costs and indirect costs did not differ before and after etanercept initiation. Discussion In this short-term study, initiation of etanercept in RA patients did not come along with a decrease of consumption of health resources. Long-term studies are needed to reveal a potential economical advantage as a consequence of the clinical, structural and functional efficacy of anti-TNF.

A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis

The HLA-DRB1 gene was reported to be associated with anticitrullinated protein/peptide autoantibody (ACPA) production in rheumatoid arthritis (RA) patients. A new classification of HLA-DRB1 alleles, reshaping the shared epitope (SE) hypothesis, was recently found relevant in terms of RA susceptibility and structural severity.We investigated the relevance of this new classification of HLA-DRB1 SE+ alleles in terms of rheumatoid factor (RF) and ACPA production in a sample of French RA patients.We studied 160 early RA patients included in a prospective longitudinal cohort of French Caucasian patients with recent-onset arthritis. RF, anticyclic citrullinated peptide 2 (anti-CCP2) and antideiminated human fibrinogen autoantibodies (AhFibA) were assessed in all patients at inclusion. The HLA-DRB1 gene was typed by PCR-sequence specific oligonucleotides probes (PCR-SSOP), and SE+ alleles were classified into four groups (S1, S2, S3P, S3D) according to the new classification.The new classification of HLA-DRB1 SE+ alleles distinguishes predisposing and protective alleles for RF, anti-CCP2 or AhFibA production. The presence of S2 or S3P alleles is associated with both RF, anti-CCP2 or AhFibA positivity, whereas the presence of S3D or S1 alleles appears to be protective for RF, anti-CCP2 or AhFibA positivity.The new classification of HLA-DRB1 SE+ alleles is relevant in terms of autoantibody production in early RA patients by differentiating predisposing and protective alleles for RF or ACPA production.

T cell receptor gamma variable gene locus polymorphism in patients with rheumatoid arthritis.

We sought new susceptibility markers for rheumatoid arthritis (RA) among the T cell receptor gamma (TCR gamma) genes. We analyzed restriction fragment length polymorphisms (RFLP) of the first variable subgroup of TCR gamma genes in a group of French control subjects and a group of French RA patients. No significant difference in Eco RI RFLP was found between the 2 study populations: Allele frequencies were virtually identical. There was no polymorphism using Hind III. These results exclude TCRV gamma I polymorphism as a disease susceptibility marker in RA.