ESPOIR Cohort Research Articles

Effect of adherence to European treatment recommendations on early arthritis outcome: data from the ESPOIR cohort

ObjectiveTo assess the association of adherence to the 2007 recommendations of the European League Against Rheumatism (EULAR) for managing early arthritis and radiographic progression and disability in patientsMethodsThe authors conducted...

Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort

ObjectiveTo identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the...

Responsiveness of EQ-5D and SF-6D in patients with early arthritis: results from the ESPOIR cohort

ObjectivesThe revolution of early aggressive treatments for early arthritis (EA) has fuelled the search for better approaches to establishing their cost–utility ratio. The authors aimed to compare the responsiveness of...

Validation of ACR/EULAR definition of remission in rheumatoid arthritis from RA practice: the ESPOIR cohort

IntroductionIn development of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) remission definitions using clinical trials data, one criterion used to compare different remission definitions was whether, compared with those not in remission, those in remission had evidence of later disease stability defined by x-ray and functional status. Validation of the RA remission criteria using observational study data is necessary before recommending their use in practice.MethodsUsing data from those who met RA criteria in the ESPOIR cohort, we matched each person in remission with a person not in remission and then carried out analyses comparing later stability of x-ray and health assessment questionnaire (HAQ) between the two groups. We compared the predictive validity of the same candidate definitions of remission evaluated in the ACR/EULAR process. To minimize potential bias and produce more stable results, we used a bootstrap resampling approach to select those not in remission, repeating the sample matching analysis process 500 times.ResultsResults were similar to those of clinical trials analyzed for the ACR/EULAR remission criteria. Specifically, the ACR/EULAR remission definitions using either an simple disease activity index (SDAI) ≤ 3.3, clinical disease activity index (CDAI) ≤ 2.8 or a definition of remission requiring tender joint count, swollen joint count, patient global assessment all ≤ 1 performed as well or better than other candidate definitions of remission in terms of predicting later x-ray and function stability.ConclusionsACR/EULAR definitions of remission developed for trials are similarly valid in observational studies in RA and could be used in practice.

Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort

IntroductionEarly rheumatoid arthritis (RA) patients may show rapid radiographic progression (RRP) despite rapid initiation of synthetic disease-modifying anti-rheumatic drugs (DMARDs). The present study aimed to develop a matrix to predict risk of RRP despite early DMARD initiation in real life settings.MethodsThe ESPOIR cohort included 813 patients from the community with early arthritis for < 6 months; 370 patients had early RA and had received methotrexate or leflunomide during the first year of follow-up. RRP was defined as an increase in the van der Heijde-modified Sharp score (vSHS) ≥ 5 points at 1 year. Determinants of RRP were examined first by bivariate analysis, then multivariate stepwise logistic regression analysis. A visual matrix model was then developed to predict RRP in terms of patient baseline characteristics.ResultsWe analyzed data for 370 patients. The mean Disease Activity Score in 28 joints was 5.4 ± 1.2, 18.1% of patients had typical RA erosion on radiographs and 86.4% satisfied the 2010 criteria of the American College of Rheumatology/European League Against Rheumatism. During the first year, mean change in vSHS was 1.6 ± 5.5, and 41 patients (11.1%) showed RRP. A multivariate logistic regression model enabled the development of a matrix predicting RRP in terms of baseline swollen joint count, C-reactive protein level, anti-citrullinated peptide antibodies status, and erosions seen on radiography for patients with early RA who received DMARDs.ConclusionsThe ESPOIR matrix may be a useful clinical practice tool to identify patients with early RA at high risk of RRP despite early DMARD initiation.

Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification criteria: an analysis based on ESPOIR cohort data

BackgroundIn 2010, new classification criteria for rheumatoid arthritis (RA) were developed.ObjectiveTo assess agreement between 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria and the...

Is routine viral screening useful in patients with recent‐onset polyarthritis of a duration of at least 6 weeks? Results from a nationwide longitudinal prospective cohort study

To study the contribution of routine viral screening tests in patients with early rheumatoid arthritis (RA) or a potential for progressing to RA. Eight hundred thirteen patients with swelling of at least 2 joints for at least 6 weeks and a symptom duration of less than 6 months in the ESPOIR cohort were screened for parvovirus B19 (IgG and IgM anti-parvovirus B19 antibodies), hepatitis B virus (HBV; hepatitis B surface antigen), hepatitis C virus (HCV; anti-HCV antibodies), and human immunodeficiency virus (HIV; anti-HIV-1 and -2 antibodies). Parvovirus B19 testing was performed in 806 patients and showed longstanding immunity in 574 (71.2%) and no antibodies in 223 (27.7%). Among the 9 remaining patients (7 IgG positive/IgM positive, 1 IgG negative/IgM positive, and 1 IgG indeterminate/IgM positive), only 2 (0.25%; 95% confidence interval [95% CI] 0-0.99%) had a positive polymerase chain reaction test for parvovirus B19; these patients (women ages 34 and 40 years) had no extraarticular signs. HIV seroprevalence was 0.12% (n = 1 of 813; 95% CI 0.01-0.8%) and HCV seroprevalence was 0.86% (n = 7 of 808, 95% CI 0.38-1.86%). HCV-related arthritis was diagnosed in 4 patients (0.5%). HCV-seropositive patients had significantly higher transaminase levels than the other patients (P = 0.001), with no significant differences for the other laboratory data. HBV seroprevalence was 0.12% (n = 1 of 808; 95% CI 0.01-0.8%); the positive HBV status was known before study inclusion, and the patient had no diagnosis of HBV-related arthritis. Finally, routine viral testing identified 2 patients with parvovirus B19 infection and 3 with HBV infection (0.6%; 95% CI 0.2-1.5%). Cost was €85.05 per patient (total €68,720). Routine serologic testing did not contribute substantially to the diagnosis in this context.

PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort

To investigate genotype-phenotype correlation and gene-environment interaction between PTPN22 R620W environmental factors such as tobacco/hormonal treatments in an inception cohort of RA patients. An intra-cohort study including 532 Caucasian RA patients genotyped for the PTPN22 rs2476601 polymorphism was performed. Anti-CCP and RF status at baseline, presence of bone erosions at 1 year, HLADR1 and/or DR4 status, demography, comorbidities, exposure to tobacco with the cumulative dose in pack-years, hormonal treatments and treatments received for RA were collected. Logistic regression was performed to estimate the ORs and multiplicative interaction with adjustment for confounding factors. Gene-environment interaction was estimated by the relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (SI). PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P < 0.0001]. Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status. No evidence for a gene-environment interaction was detected. These data provide new insights into the pathogenesis of RA, underlying the pivotal key role of environmental factors in the typical heterogeneity of RA.

Favorable effect of very early disease-modifying antirheumatic drug treatment on radiographic progression in early inflammatory arthritis: Data from the Étude et Suivi des Polyarthrites IndifféRenciées récentes (Study and Followup of Early Undifferentiate

While there is consensus that treatment with disease-modifying antirheumatic drugs (DMARDs) should be started early in patients with inflammatory arthritis, confirmation that radiographic progression is inhibited with early treatment start is scarce. This study was undertaken to compare radiographic progression in patients treated with a DMARD very early in the course of their disease (within 3 months of diagnosis) and those who began DMARD treatment later. Patients included in the French observational ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes [Study and Followup of Early Undifferentiated Polyarthritis]) cohort were followed up, and radiographic progression after 12 months was assessed. Propensity scores, reflecting the indication to start a DMARD, were obtained by modeling the start of DMARD therapy by disease-specific and demographic variables obtained at baseline, using logistic regression analysis. The influence of very early versus delayed DMARD start on radiographic progression was evaluated by generalized linear regression, with and without adjustment for propensity scores. Six hundred sixty-one patients were analyzed. In an unadjusted analysis, patients starting DMARD therapy within 3 months of diagnosis did not show a significant difference in radiographic progression score as compared to those starting DMARD therapy later (1.2 units versus 1.6 units; P = 0.37). Adjustment for the propensity score revealed a statistically significant difference in mean progression (0.8 units versus 1.7 units; P = 0.033). Analysis by propensity score quintile showed a trend suggesting that early treatment was especially beneficial for patients in the fourth and fifth quintiles (worse prognosis). Our findings indicate that among patients with inflammatory arthritis in daily clinical practice, early initiation of DMARD therapy reduces 12-month radiographic progression. This strengthens the current recommendations for very early initiation of specific therapy in patients with early arthritis.

Comparison of the EQ-5D and the SF-6D Utility Measures in 813 Patients with Early Arthritis: Results from the ESPOIR Cohort

The revolution of early aggressive therapy in early arthritis (EA) has fueled the search for better approaches to establish cost-effectiveness. Our objective was to compare the EuroQol EQ-5D health outcome measure and the SF-6D and to investigate their relationship to clinical variables in a large prospective cohort of patients with EA. The EQ-5D and SF-6D utility measures were longitudinally assessed in 813 patients with EA. Agreement and aspects of validity (construct validity, discrimination) were assessed. At baseline, mean values for EQ-5D were 0.52 ± 0.31 (range -0.59 to 1.0) and for SF-6D were 0.58 ± 0.11 (range 0.30 to 0.92), with a bimodal distribution for the EQ-5D. Agreement was low for patients with severe disability or active disease: the utility was systematically lower with EQ-5D. The intraclass correlation coefficient was 0.42 at baseline and increased to 0.53 at 6 months and 0.57 at 1 and 2 years. Correlations between the 2 utility scores and the Health Assessment Questionnaire were good, and remained similar and stable over 2 years (r = -0.70). Correlations with the Disease Activity Score for 28 joints and the physical component of the MOS 36-item Short-form Health Survey (SF-36) were moderate to good and stable. In contrast, correlation with the mental component of the SF-36 was better with the SF-6D, and the correlation with pain, weak at baseline, improved at 6 months and remained stable thereafter. The SF-6D was better able to discriminate patients with high disease activity. There was systematic disagreement between EQ-5D and SF-6D in EA, especially in patients with worse clinical outcomes. Using the 2 instruments could be appropriate to conduct sensitivity analyses of cost-utility ratios because the instruments measure utility with closely similar measured properties, but at different levels.

Diagnostic performance of three assays for anticitrullinated protein antibodies in the very early arthritis ‘ESPOIR’ cohort

Background and objectivesAnticitrullinated protein antibodies (ACPA) are recognised as the most specific markers for rheumatoid arthritis (RA). Their detection can be performed with various ELISAs using either the autoantigenic targets...

Musculoskeletal Ultrasonography in Healthy Subjects and Ultrasound Criteria for Early Arthritis (The ESPOIR Cohort)

To confirm the occurrence of bone erosions and synovitis in healthy subjects detectable by ultrasound (US) and to establish US criteria for early arthritis. Our study involved 127 healthy subjects matched with a cohort of patients with early arthritis (the ESPOIR cohort). The second and fifth metacarpophalangeal (MCP) joints and the fifth metatarsophalangeal (MTP) joint of both hands and feet were assessed with US to detect bone erosion; and the second, third, fourth, and fifth MCP and the fifth MTP were evaluated for synovial thickening in B-mode US and synovial vascularity in power Doppler. Bone erosion and synovitis were defined according to the Outcome Measures in Rheumatology Clinical Trials consensus. Bone erosion and grade 2-3 synovial thickening in B-mode were detected in 11% and 9% of healthy subjects. To consider the diagnosis of early arthritis, a cutoff at 1 case of synovial thickening in B-mode enabled discrimination between patients with early arthritis and healthy subjects, with a good sensitivity of 74.8% (95% CI 67.2%-82.3%) and a high specificity of 90.5% (95% CI 85.4%-95.6%). If higher specificity is required to confirm the diagnosis of early arthritis, cutoff at 2 cases of synovial thickening in B-mode or at 2 cases of bone erosion gave optimal results, with specificity of 98.4% (95% CI 96.2%-100%) and 100%, respectively, and lower sensitivity of 59.8% (95% CI 51.2%-68.3%) and 17% (95% CI 10.5%-23.5%) (area under the curve = 0.85 for synovitis and 0.63 for bone erosion). Neither the combination of power Doppler signal plus bone erosion, nor bone erosions plus synovial thickening on the same joint, were seen in healthy subjects. A single case of bone erosion or synovial thickening in B-mode is common in healthy subjects. However, more than 1 case of synovial thickening in B-mode or bone erosion is a strong argument for the diagnosis of early inflammatory arthritis.

Disease activity score-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort

ObjectivesTo compare the efficacy of disease activity score in 28 joints (DAS28ESR)-driven therapy with anti-tumour necrosis factor (patients from the GUEPARD trial) and routine care in patients with recent-onset rheumatoid...

Disease activity score-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort

Disease activity score-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort

Hormonal replacement therapy may reduce the risk for RA in women with early arthritis who carry HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP: results from the ESPOIR cohort

ObjectiveTo assess the effect of reproductive factors, especially hormone replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of rheumatoid arthritis (RA) and the...

Is Screening for Hepatitis B and Hepatitis C Useful in Patients with Recent-Onset Polyarthritis? The ESPOIR Cohort Study

To evaluate the seroprevalence of hepatitis B (HBV) and C (HCV) in patients living in France with recent-onset polyarthritis suggesting rheumatoid arthritis. The 813 patients in the ESPOIR cohort were screened for anti-HCV antibodies and HBs antigen. Seroprevalence was 0.86% for HCV (n = 7) and 0.12% for HBV (n = 1). HCV-related arthritis was diagnosed in 4 (0.5%) patients; no patient had HBV-related arthritis. HCV-seropositive patients had significantly higher transaminase levels (ALAT, 41.5 IU vs 23.2 IU, p = 0.02; and ASAT, 39.2 IU vs 21.8 IU, p = 0.001) but only 2 patients had ASAT or ALAT levels > 40 IU. No significant differences were found for anti-CCP antibodies, C-reactive protein, erythrocyte sedimentation rate, or other test. HCV seroprevalence was significantly higher in the subgroup with history of blood transfusion than in other patients (3.7% vs 0.42%, p = 0.02). Two of the 7 HCV positive patients and the single patient with confirmed hepatitis B infection were born in areas with higher prevalence of viral hepatitis (Togo, Senegal, Vietnam). Positive hepatitis status was known before study inclusion in 4 of the 7 HCV-positive patients and in the HBV-positive patient. The prevalence of HBV and HCV in a population of patients with recent-onset polyarthritis suggestive of RA was not greater than expected based on data from the general population in the same geographic area. Routine HBV and HCV serological testing did not contribute substantially to the diagnosis of recent-onset polyarthritis. Although advisable before initiating immunosuppressive or hepatotoxic drugs, serological testing for HCV and HBV is unnecessary in routine diagnostic evaluation of recent-onset polyarthritis.

The Gap Between Practice and Guidelines in the Choice of First-line Disease Modifying Antirheumatic Drug in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort

To compare rheumatologists' prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines. Method. ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. "Definite" and "probable" RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients' usual rheumatologists to investigate the reasons for their nonconformity with guidelines. In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist. There is a substantial gap between CPG and rheumatologists' daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA.

Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort

IntroductionLittle is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort.MethodsIn the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients.ResultsAll markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA.ConclusionsMarkers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.

Ability of oblique foot radiographs to detect erosions in early arthritis: Results in the ESPOIR cohort

To assess the usefulness of using oblique foot radiographs in addition to posteroanterior radiographs of the hands and feet for detecting erosions in patients with recent-onset arthritis. We included 813 patients from the prospective French ESPOIR cohort with arthritis of <6 months' duration and >or=2 swollen joints. Baseline standardized posteroanterior radiographs of the hands and feet and oblique radiographs of the feet were assessed by 2 blinded readers for erosions typical for rheumatoid arthritis (ETRA) and the Sharp score as modified by van der Heijde. A total of 715 complete sets were available. Mean +/- SD total Sharp scores were 3.6 +/- 6.6, 2.5 +/- 6.3, and 1.8 +/- 5 for the hand and wrist, foot, and oblique foot, respectively. ETRA were visible in 160 (22.4%) of 715 patients (95% confidence interval [95% CI] 19.4-25.6). They were seen on hand radiographs in 86 (53.7%) of 160 patients (95% CI 45.7-61.6), on posteroanterior foot radiographs in 91 (56.9%) of 160 patients (95% CI 48.8-64.6), and on oblique foot radiographs in 84 (52.5%) of 160 patients (95% CI 44.5-60.4). ETRA were visible at the feet, but not at the hands, in 74 (46%) of 160 patients (95% CI 38.4-54.3), among whom 22 (30%) had erosions only on the posteroanterior view, 16 (21%) only on the oblique view, and 36 (48.6%) on both. ETRA were found in 22.4% of patients. Adding an oblique foot radiograph identified 16 (10%) of 160 additional patients (95% CI 6-16), compared with 27.5% and 13.8% identified by adding posteroanterior radiographs of the hands and feet, respectively.

The ESPOIR cohort: A ten-year follow-up of early arthritis in France: Methodology and baseline characteristics of the 813 included patients

Objectives The French Society of Rheumatology initiated a large national multicenter, longitudinal and prospective cohort, the so-called “ESPOIR cohort study” in order to set up databases to allow various investigations on diagnosis, prognostic markers, epidemiology, pathogenesis and medico-economic factors in the field of early arthritis and rheumatoid arthritis. Methods Patients were recruited if they had undifferentiated arthritis or rheumatoid arthritis, of less than 6 months disease duration and if they were DMARD and steroids naïve. Patients have then to be followed every 6 months during the first 2 years then every year during at least 10 years. Clinical, biological, radiographic and medico-economic databases have been constituted to fit in the different objectives of the project and more than 20 scientific studies have already been accepted by the scientific committee. Results 813 patients were included (76.75% were female). The mean age was 48.07 ± 12.55 years. The mean delay from the onset of symptoms to referral to the rheumatologist was 74.8 ± 76.6 days. Baseline swollen and tender joint counts were 7.19 ± 5.37 and 8.43 ± 7.01; DAS28 score was 5.11 ± 1.31. CRP was abnormal in 38.9% of the patients; 44.2%, 45.8% and 38.8% had respectively IgM rheumatoid factor (RF), IgA RF and anti-CCP antibodies. HLA DRB1*01 or 04 genes were found in 56.7% of them. Finally, 22% of these patients had erosions on hand or feet at baseline.