DAS28-γGT for the prediction of major cardiovascular events in rheumatoid arthritis: results from the ESPOIR cohort.

OBJECTIVE: To validate the predictive value of the DAS28 γ-glutamyl transferase (DAS28-γGT) for the occurrence of major cardiovascular (CV) events (MACE) in the 'Etude et Suivi des Polyarthrites Indifférenciées Récentes' ESPOIR cohort. METHODS: Analysis of 13-year outcome from the ESPOIR cohort. RA patients with missing data for baseline γGT activity and those not followed-up to 1 year were excluded. Baseline DAS28-γGT was calculated using the following formula: 0.56*√TJ-28 + 0.28 * √SJ-28 + 2*ln(γGT) + 0.014 * GH. Our primary outcome was the merit of the DAS28-γGT in predicting the occurrence of MACE. RESULTS: Among the 696 patients [536 women, mean (s.d.) age of 49 (12) years], 34 MACE were recorded, with a mean time to event of 71 (44) months. Receiver operating characteristic curve analysis indicated that a DAS28-γGT >9.4 had the best sensitivity and specificity for the diagnosis of MACE during the observation period. DAS28-γGT >9.4 was predictive of the occurrence of MACE, with a hazard ratio (HR) of 3.11 (95% CI 1.41, 5.43). Multivariate Cox analyses confirmed higher DAS28-γGT (HR 2.44, 95% CI 1.05, 5.64) together with age (HR 1.04, 95% CI 1.01, 1.07) and diabetes mellitus (HR 4.12, 95% CI 1.55, 10.95) as independent predictors of MACE. There was a dose effect of the DAS28-γGT for MACE-risk prediction, which was in line with the application of the Framingham risk score. CONCLUSION: The DAS28-γGT was identified in this large prospective cohort as an independent predictor of MACE in patients with RA. The DAS28-γGT is a simple and useful tool to evaluate CV risk in routine and warn the clinician about the CV risk burden in patients with RA.

Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis.

OBJECTIVES: To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. METHODS: Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. RESULTS: This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. CONCLUSION: Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.

Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early rheumatoid arthritis.

OBJECTIVES: To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA. METHODS: Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. RESULTS: Among the 608 patients [480 women, mean age of 47.5 (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6-4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35). CONCLUSION: The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. TRIAL REGISTRATION: (ClinicalTrials.gov Identifier: NCT03666091).

Current favourable 10-year outcome of patients with early rheumatoid arthritis: data from the ESPOIR cohort.

OBJECTIVE: To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. METHODS: From 2003 to 2005, 813 patients were included if they had early arthritis (<6 months) with a high probability of RA and had never been prescribed DMARDs. Multivariate analysis was used to evaluate predictors of outcome. RESULTS: In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. CONCLUSIONS: We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort.

BACKGROUND: Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. OBJECTIVE: To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. METHODS: Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. RESULTS: Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. CONCLUSION: Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.

Seven-year tolerability profile of glucocorticoids use in early rheumatoid arthritis: data from the ESPOIR cohort.

OBJECTIVE: To explore the 7-year tolerability profile of glucocorticoids (GC) for early rheumatoid arthritis (RA). METHODS: We examined data for 602 patients with RA from the early arthritis Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort (<6 months disease duration) stratified into two groups: with or without GC treatment at least once during follow-up (median 7 years (IQR 0.038-7.65)). The main outcome was a composite of death, cardiovascular disease (including myocardial ischaemia, cerebrovascular accident and heart failure), severe infection and fracture. RESULTS: Among the 602 patients with RA (476 women (79%), mean age 48±12 years), 386 with GC (64.1%) received low-dose prednisone (mean 3.1±2.9 mg/day for the entire follow-up): 263 started GC during the first 6 months (68%), and the mean duration of total GC treatment was 1057±876 days. As compared with patients without GC (216 (35.9%)), those with GC showed greater use of non-steroidal anti-inflammatory drugs, synthetic and biological disease-modifying antirheumatic drugs and had more active disease disability, higher C reactive protein and anticitrullinated protein antibody levels. Among 65 events (7 deaths, 14 cardiovascular diseases, 19 severe infections and 25 fractures), 44 and 21 occurred in patients with and without GC (p=0.520). Infections were more frequent, although not significantly, in patients with than without GC (p=0.09). On weighted Cox proportional-hazards analysis, with use of propensity score and inverse-probability-of-treatment weighting, and including age, gender, history of hypertension and GC treatment, outcomes did not differ with and without GC (p=0.520; HR=0.889; 95% CI 0.620 to 1.273). CONCLUSIONS: This 7-year analysis of the ESPOIR cohort supports the good safety profile of very low-dose GC for early active RA.

Management of dyslipidaemia in high-risk patients with recent-onset rheumatoid arthritis: targets still not met despite specific recommendations. Results from the ESPOIR cohort during the first five years of follow-up.

OBJECTIVES: Reduction of LDL-cholesterol (LDLc) is essential to decrease the cardiovascular mortality in rheumatoid arthritis (RA). Between 2005 and 2010, French recommendations for dyslipidaemia defined the LDLc target based on the number of cardiovascular risk factors. In 2006, it was recommended to consider LDLc objectives with RA being counted as an additional cardiovascular risk factor. Our objective was to assess lipid target achievement between 2006 and 2010 in a cohort of patients with recent-onset RA. METHODS: 814 patients were included between 2002 and 2005 in a French cohort of patients with early arthritis and a high probability of RA (ESPOIR). Repeated cross-sectional analyses for cardiovascular risk factors, cholesterol levels were performed every year from 2006 to 2010 to determine lipid profile and achievement of the LDLc goal according to the French guidelines. RESULTS: On the 620 patients analysed at the first point, 77% were female, 89.8% fulfilled the ACR criteria for RA and 2.7% received a statin. The proportion of patients failing to achieve the LDLc target did not improve following the publication of specific RA guidelines in 2006 (15.3 to 22.5% between 2006 and 2010). In patients with the highest cardiovascular risk, more than 58% did not reach the LDLc target. CONCLUSIONS: Specific recommendations for RA published in 2006 decreased LDLc target but did not improve management of dyslipidaemia in daily life which remained suboptimal particularly in patients at highest risk.

Psychological distress over time in early rheumatoid arthritis: results from a longitudinal study in an early arthritis cohort.

OBJECTIVE: RA is a chronic disease with frequent psychological co-morbidities, of which depression and anxiety are two common manifestations. We aimed to identify predictive factors of psychological distress in a large prospective cohort of very early RA patients. METHODS: ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) is a multicentre, longitudinal and prospective cohort study of patients with early arthritis (<6 months disease duration). The study sample comprised 641 patients with very early RA according to the 2010 ACR/European League Against Rheumatism RA criteria from the ESPOIR cohort. Psychological distress was assessed over 3 years by the five-item Mental Health Inventory questionnaire at various time points (baseline, 6, 12, 18, 24 and 36 months). Logistic regression with a generalized estimating equation model was used to analyse the association of disease variables and risk of psychological distress. RESULTS: At baseline, 46.9% of RA patients were screened as positive for psychological distress. Over 3 years, psychological distress decreased significantly, with a prevalence of 25.8% at 36 months. The HAQ Disability Index (HAQ-DI) score was the most important factor predicting psychological distress over 3 years [odds ratio 2.10 (95% CI 1.41, 3.14)-3.59 (2.29, 5.63)]. Baseline biological and radiological variables and treatment regimens were not associated with distress. CONCLUSION: Psychological distress in very early RA is frequent and the HAQ-DI score is a predictor of depression and anxiety in these patients. A psychological evaluation in patients with early RA is important for further individual psychiatric diagnosis and management.

The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort.

OBJECTIVE: To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. METHODS: Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. RESULTS: Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. CONCLUSION: Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA.

Defining erosive disease typical of RA in the light of the ACR/EULAR 2010 criteria for rheumatoid arthritis; results of the data driven phase.

BACKGROUND: According to the 2010 criteria, rheumatoid arthritis (RA) can be classified in the presence of ≥6 points on the criteria or 'typical' erosive disease. RA-specific erosiveness however has not been defined yet. This study reports the results of the data driven phase of a European League Against Rheumatism (EULAR) taskforce aiming to define RA-specific erosiveness. METHODS: Baseline radiographs of hands and feet of 980 Dutch and 811 French early arthritis patients were studied on the number and site of erosive joints. Test characteristics were determined, with the outcome measures being initiation of methotrexate (MTX) therapy or any disease modifying antirheumatic drug (DMARD) therapy within the first year of disease and arthritis persistency over 5 years. Analyses were repeated in the patients with <6 points on the American College of Rheumatology/EULAR 2010 criteria. RESULTS: In both cohorts comparable test characteristics were observed for the outcomes MTX therapy, any DMARD therapy and arthritis persistency. Test characteristics were not influenced by the site of erosiveness. The specificity observed was >50% for ≥1 erosive joint, >80% for ≥3 erosive joints and >90% for ≥5 erosive joints. When analysing the patients not fulfilling the 2010 criteria (n=308 and 149), specificity was >60% for ≥1 erosive joint, >90% for ≥3 erosive joints and >95% for ≥5 erosive joints. Few of these patients fulfilled the radiological criterion; 27-36 patients had ≥3 erosive joints and 13-14 patients had ≥5 erosive joints. CONCLUSIONS: RA-specific erosiveness can be defined with high specificity at several cut-offs for the number of erosive joints in two independent cohorts with multiple different outcomes. The final radiological criterion will be established in the next phase.

Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data from the French ESPOIR cohort.

OBJECTIVES: To compare the performance of anticitrullinated peptides/protein antibodies (ACPA) detected by three immunoassays in the French ESPOIR cohort of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) and to study the relationship between ACPA and disease activity. METHODS: A diagnosis of RA (1987 American College of Rheumatology (ACR) criteria) was established at baseline in 497 patients and after a 2-year follow-up in 592 patients. At baseline, antibodies to citrullinated fibrinogen (AhFibA), antimutated citrullinated vimentin (anti-MCV) and anticyclic citrullinated peptide (anti-CCP2) were assayed and the individual and combined diagnostic sensitivities and predictive values of the tests were determined. Relationships between ACPA positivity and the 28-joint disease activity score and Health Assessment Questionnaire scores were analysed. RESULTS: At a diagnostic specificity of at least 98%, the three tests exhibited similar diagnostic sensitivities (47-48.5%). When considering as positive patients with at least one positive test, the sensitivity increased to 53.5% with a probable loss of specificity. Among the patients classified as having UA at baseline, 30% were positive for one ACPA, the positive predictive values for RA of the three tests ranging from 73% to 80% but increasing when two tests were associated. Whatever the test used, the addition of ACPA positivity to the 1987 criteria enhanced their sensitivity by 6%, close to that of the 2010 ACR/European League Against Rheumatism (EULAR) criteria. CONCLUSIONS: In early arthritis, AhFibA, anti-MCV and anti-CCP2 showed similar diagnostic sensitivity with a high diagnostic specificity and a similar high positive predictive value for RA. Adding ACPA to the 1987 ACR criteria significantly increased the number of patients classified as having RA, confirming the validity of the recent inclusion of the serological criterion in the ACR/EULAR criteria.

Birth Outcomes in DES Children and Grandchildren: A Multigenerational National Cohort Study on Informative Families.

OBJECTIVE: Diethylstilbestrol (DES), a potent synthetic nonsteroidal estrogen belonging to the family of endocrine disrupting chemicals (EDCs), can cross the placenta and may cause permanent adverse health effects in the exposed mothers, their children (exposed in utero), and also their grandchildren through germline contribution to the zygote. This study evaluated pregnancy duration and birthweight (BW) variations in the children and grandchildren born before, during, and after maternal DES treatment in the same informative families, to rule out genetic, endocrine, and environmental factors. DESIGN AND SETTING: Nationwide retrospective observational study on 529 families of DES-treated women registered at the HHORAGES-France Association. The inclusion criteria were: (i) women with at least three pregnancies and three viable children among whom the first was not exposed in utero to DES, followed by one or more children with fetal exposure to DES, and then by one or more children born after DES treatment; (ii) women with at least one pre-DES or post-DES grandchild and one DES grandchild; (iii) confirmed data on total DES dose. Women with severe pathologies or whose illness status, habitat, lifestyle habits, profession, treatment changed between pregnancies, and all mothers who reported pregnancy-related problems, were excluded. RESULTS: In all, 74 women met all criteria. The preterm birth (PTB) rate was 2.7% in pre-DES, 14.9% in DES, and 10.8% in post-DES children (Cochran-Armitage test for trend, p = 0.0095). The mean BW was higher in DES than pre-DES full-term neonates (≥37 weeks of gestation) (p = 0.007). In grandchildren, BW was not different, whereas the PTB and low BW rates were slightly increased in children of DES women. CONCLUSIONS: These data within the same informative families show the DES impact on BW and PTB in DES and post-DES children and grandchildren. In particular, mean BW was higher in DES than pre-DES full-term neonates. This result may be in opposition to previous data from American cohorts, which reported lower BW in DES children, but is consistent with animal study. Our retrospective observational study highlights a multigenerational and likely transgenerational effect of this EDC in humans.

Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.

OBJECTIVE: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). METHODS: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). RESULTS: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (ß = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (ß = 0.24 [95% CI 0.14, 0.34]), less exercise (ß = 0.17 [95% CI 0.09-0.25]), and less education (ß = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. CONCLUSION: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.

Validation in the ESPOIR cohort of vitamin K-dependent protein S (PROS) as a potential biomarker capable of predicting response to the methotrexate/etanercept combination.

BACKGROUND: To validate the ability of PROS (vitamin K-dependent protein S) and CO7 (complement component C7) to predict response to the methotrexate (MTX)/etanercept (ETA) combination in rheumatoid arthritis (RA) patients who received this therapeutic combination in a well-documented cohort. METHOD: From the ESPOIR cohort, RA patients having received the MTX/ETA or MTX/adalimumab (ADA) combination as a first-line biologic treatment were included. Serum concentrations of PROS and CO7 were measured by ELISA prior to the initiation of ETA or ADA, at a time where the disease was active (DAS28 ESR > 3.2). The clinical efficacy (response/non-response) of both combinations has been evaluated after at least 6 months of treatment, according to the EULAR response criteria with some modifications. RESULTS: Thirty-two were treated by MTX/ETA; the numbers of responders and non-responders were 24 and 8, respectively. Thirty-three patients received the MTX/ADA combination; 27 and 5 patients were respectively responders and non-responders. While there were no differences for demographic, clinical, biological, and X-rays data, as well as for CO7, serum levels of PROS tended to be significantly higher in responders to the MTX/ETA combination (p = 0.08) while no difference was observed in the group receiving MTX/ADA. For PROS, the best concentration threshold to differentiate both groups was calculated at 40 µg/ml using ROC curve. The theranostic performances of PROS appeared better for the ETA/MTX combination. When considering the response to this combination, analysis of pooled data from ESPOIR and SATRAPE (initially used to validate PROS and CO7 as potential theranostic biomarkers) cohorts led to a higher theranostic value of PROS that became significant (p = 0.009). CONCLUSION: PROS might be one candidate of a combination of biomarkers capable of predicting the response to MTX/ETA combination in RA patients refractory to MTX. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03666091 and NCT00234234 .

Early referral to the rheumatologist for early arthritis patients: evidence for suboptimal care. Results from the ESPOIR cohort.

OBJECTIVE: To assess the time to access a rheumatologist (TTAR) by early arthritis (EA) patients participating in a nationwide incidental cohort (ESPOIR) and compare it with European League Against Rheumatism (EULAR) recommendations, which recommends rapid referral, ideally within 6 weeks, to a rheumatologist for patients presenting with EA. METHODS: Eight hundred and thirteen patients with EA were included in the cohort between 2002 and 2005. The inclusion criteria were 18-70 years old, two or more swollen joints, symptom duration from 6 weeks to 6 months and possible RA diagnosis. TTAR was defined as the time between the first synovitis and first visit to a rheumatologist. TTAR and satisfaction of the EULAR guidelines were investigated by multiple linear and logistic regressions. RESULTS: Mean TTAR was 76 days; only 46.2% of patients were seen by a rheumatologist within the EULAR-recommended time frame. Patients' patterns of accessing medical care substantially affected access to specialized care: mean TTAR was 58 days for patients who directly scheduled an appointment with the rheumatologist and 78 days for those referred by their general practitioner (P < 0.0007). Only 57.2 and 44.5%, respectively, were able to consult a rheumatologist within 6 weeks. Multivariate analysis confirmed the significant impact of indirect access on TTAR, after adjustment for EA characteristics and medical density in the region. CONCLUSIONS: Significant disparities were identified in the care of EA patients in terms of early access to a rheumatologist. More effort is needed to optimize the physicians' knowledge about EA and to improve the efficiency of medical networks.

Association Between Vitamin D Deficiency and Disease Activity, Disability, and Radiographic Progression in Early Rheumatoid Arthritis: The ESPOIR Cohort.

OBJECTIVE: To evaluate the association of baseline serum level of vitamin D with disease activity, disability, and radiographic damage over the first year in early rheumatoid arthritis (RA). METHODS: Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and van der Heijde modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitamin D level and radiographic progression (mTSS increased by ≥ 1 point) or disability (HAQ-DI ≥ 0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes. RESULTS: Among 813 patients with early arthritis, data for 645 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10-29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency compared with groups 2 and 3 combined (P = 0.007 and P = 0.001, respectively), as was mean mTSS, but not significantly (p = 0.076). On multivariate analysis, baseline vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76). CONCLUSION: Vitamin D deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients. [ClinicalTrials.gov: NCT03666091].

Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort.

OBJECTIVE: To describe the disease course of patients with early arthritis without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) for these patients within 3 years. METHOD: Patients included in the multicenter ESPOIR cohort were compared at baseline and 3 years by whether they were negative for RF and ACPA ("seronegative") or positive for RF and/or ACPA ("seropositive"). Univariate analysis was used to determine the association between baseline variables in seronegative patients and RA classification. Stepwise multiple logistic regression was used to identify predictors of RA classification within 3 years, estimating odds ratios (ORs). RESULTS: Among 354 seronegative patients, 224/340 with available data (65.9%) fulfilled RA classification at baseline and 189/233 (81.1%) at 3 years. As compared with seropositive patients, seronegative patients had lower DAS28 (p = 0.002) and lower modified total Sharp score (mTSS; p = 0.026) at baseline; DAS28 remission was similar (p = 0.634), but radiographic progression rate was lower in seronegative patients (p <  0.001) at 3 years. In seronegative patients, factors predicting RA classification within 3 years were additive (OR = 3.61), bilateral (OR = 2.59) and hand, wrist or forefeet involvement (OR = 3.87); presence of a trigger event (OR = 3.57); pain at rest (OR = 2.76); morning stiffness (OR = 2.62); number of tender joints (OR = 23.73); and mTSS (OR = 2.56). CONCLUSION: "Seronegative" patients have less active disease at baseline and less radiographic progression during follow-up than "seropositive" patients. With inflammatory pain, symmetric involvement of numerous small joints and erosive disease, a classification of RA is likely.

Early lessons from the recent-onset rheumatoid arthritis cohort ESPOIR.

ESPOIR is a French multicenter cohort of patients with undifferentiated arthritis enrolled within six months of symptom onset, naive to disease-modifying antirheumatic drugs and corticosteroid therapy, and either having rheumatoid arthritis (RA) or being at risk for progression to RA. The cohort is sponsored by the French Society for Rheumatology (Société française de rhumatologie [SFR]). Between December 2002 and March 2005, 813 patients were enrolled at 14 regional university hospitals, with the participation of a network of community-based rheumatologists. The objective was to establish a database on recent-onset inflammatory joint disease and, more specifically, on RA to serve for scientific research in the clinical, epidemiological, pathophysiological, and healthcare-cost fields. Ten years after enrolment were started, the cohort still has about 500 patients. The scientific committee has approved 104 clinical research projects, of which many are ongoing, and 54 original articles written by numerous French and international groups have been published. These projects cover a vast spectrum of topics including environmental factors, diagnosis, outcomes, prognosis, disease evaluation, imaging, genetics, biomarkers, costs, and RA management strategies.

Prevalence and concordance of early and sustained remission assessed by various validated indices in the early arthritis "ESPOIR" cohort.

OBJECTIVES: To assess the prevalence of remission in early arthritis, to evaluate the concordance across different criteria sets in defining this state, and to look for predictive factors for early and sustained remission. METHODS: Patients from the ESPOIR cohort were followed-up every 6months. We analysed early remission and sustained remission in 3 groups of patients: patients having rheumatoid arthritis (RA) according to 2010 ACR/EULAR criteria, undifferentiated arthritis (UA), and the whole cohort. Remission was defined according to ACR/EULAR criteria, 28 Joint Disease Activity Score (DAS28<2.6), and Simplified Disease Activity Index (SDAI≤3.3). Agreement was evaluated by k-coefficient. Predictive factors for sustained remission at 1, 3 and 5year in RA patients were analyzed. RESULTS: Eight hundred and nineteen patients were included. Early remission rates in the RA/UA/ESPOIR groups were observed in respectively 29.2% (181/682), 51.4% (55/123) and 32.7% (239/813) of patients by DAS28; 15.7%, 29.1% and 18% by SDAI; and 11.2%, 29.1% and 12.8% by ACR/EULAR criteria. Agreement between classifications of remission was low for DAS28 vs. ACR/EULAR (k=0.44), high for SDAI vs. ACR/EULAR (k=0.78), and moderate for SDAI vs. DAS28 (k=0.54). Lower baseline disease activity scores, non-menopausal status and younger age were the best predictive factors for sustained remission, with consistent results across the 3 definitions of remission. CONCLUSION: Our study showed that the rate of early and sustained remission in early arthritis is dependent on the definition used, with a variable degree of agreement across criteria sets, but with consistent predictive factors of favourable outcome in patients finally diagnosed with RA.