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.

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. METHODS: VErA-cohort patients were prospectively recruited from 1998 to 2002. Arthritis treatment was standardised from onset. The clinical, biological and radiological parameters of all patients were collected from inclusion. Carotid intima-media thickness (cIMT) was measured 7 years after their first symptoms. RESULTS: Among 105 patients included, 82 developed RA (mean age at onset: 51.7±12.8 years). Mean carotid artery IMT at year 7 was 0.67±0.12 mm. Larger thickness defined by values above the median (0.66) was associated with inclusion age (p<10-6), swollen joint count (p=0.01), DAS44 (p=0.048) and hypertension (p=0.006). In contrast, anti-CCP positivity (>50 UA/ml) was associated with thinner cIMT (p=0.03). Baseline as well as cumulated values of markers reflecting systemic inflammation, lymphocyte activation, endothelial dysfunction and oxidative stress were not correlated with carotid subclinical atherosclerosis. Major independent atheroma risk factors retained by multivariate analyses were hypertension (OR 4.33 [1.59-11.73]; p=0.004) and swollen joint count at inclusion (OR 3.87 [1.54-9.72]; p=0.004), while methotrexate use was a protective marker (OR 0.27 [0.11-0.71]; p=0.007). CONCLUSIONS: This study conducted from the VErA vascular cohort of community-cases of RA confirm that cIMT is under the influence of classical CV risk (hypertension), disease marker (SJC) and methotrexate intake.

Combining anti-cyclic citrullinated peptide with the American College of Rheumatology 1987 criteria failed to improve early rheumatoid arthritis diagnosis in the community-based very early arthritis cohort.

OBJECTIVES: To test the performances of combining anti-CCP second generation (CCP2) with ACR 1987 classification criteria and to diagnose early RA in a community-based very early arthritis (VErA) patient cohort. METHODS: The VErA cohort comprised 310 patients (median age 52 years; 68.1% women; median symptom duration 4.2 months; glucocorticoid- and DMARD naïve) conservatively treated during the first 2 years. At 6 years of follow-up, a three-expert committee classified the patients into three groups: RA, other classified arthritis (OCA) or unclassified arthritis (UA). We calculated the performances of the different sets, including anti-CCP2 positivity, while retaining or deleting RF and rheumatoid nodule components with ACR 1987 criteria for early RA diagnosis. Models were subjected to receiver operating characteristics curve and logistic regression analyses to try to identify relevant sets able to classify very early RA. RESULTS: At 6 years, 149 patients were diagnosed as RA and 119 as non-RA (95 OCA and 24 UA). The original ACR 1987 criteria had 77.9% sensitivity and 64.7% specificity for the RA diagnosis at 6 years. The modified set excluding rheumatoid nodules, including anti-CCP2 positivity and retaining RF performed significantly better than ACR 1987 criteria, with 79.9% sensitivity and 64.7% specificity and with a larger area under the curve. However, in the zone of interest, i.e., ≥4/7 criteria, the curves for these sets were superimposed. CONCLUSIONS: Adding anti-CCP2 positivity and deleting rheumatoid nodules failed to improve the performances of ACR 1987 classification criteria for the diagnosis of early RA.

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). Two gold standards were used: expert diagnosis at six years and EULAR erosive disease at two years. RESULTS: At inclusion, median age was 52 years; median RA duration 4.2 months. 2010-ACR/EULAR criteria, including EULAR-defined erosive disease applied at baseline, classified comparable numbers of patients as the 1987 criteria (P=0.27). Using expert diagnosis at six years, more patients were classified as RA with S2 than 1987-ACR criteria (P<0.04). In contrast, sensitivity and specificity indicated that 2010-ACR/EULAR-S3 criteria performed slightly but not significantly better than 1987-ACR criteria. On ROC curves, a score ≥ 6 correctly classified RA. When EULAR-defined erosion at two years was the gold standard, the 1987-ACR, the 2010-S1, -S2 and -S3 criteria performed comparably. CONCLUSIONS: Using the very early community-based, conservatively treated VErA cohort, the strict application of 2010-ACR/EULAR criteria using the new EULAR definition of erosive disease or not performed slightly but not significantly better than the 1987-ACR criteria.

Prediction of radiographic damage in early arthritis by sonographic erosions and power Doppler signal: a longitudinal observational study.

OBJECTIVE: To assess the ability of ultrasonography (US) to predict radiographic damage in early arthritis. METHODS: ESPOIR is a multicentric cohort of early arthritis (i.e., ≥2 swollen joints between 6 weeks and 6 months). US synovitis in B mode, power Doppler (PD) mode, and erosions were searched on the second through the fifth metacarpophalangeal and fifth metatarsophalangeal joints according to Outcome Measures in Rheumatology definitions. Structural radiographic progression was assessed using the modified Sharp/van der Heijde erosion score (SHS) at baseline and 1 and 2 years. Predictive factors of erosive arthritis at 2 years and rapid radiographic progression (RRP) at 1 year (defined by change of SHS ≥5) were searched. RESULTS: A total of 127 patients were included, with a mean ± SD Disease Activity Score in 28 joints of 5.1 ± 1.3; 37.6% were anti-citrullinated protein antibody positive and 27.6% had typical rheumatoid arthritis (RA) erosions on radiographs. At 2 years, 42 patients (39.2%) had typical RA erosions. US erosions predicted radiographic evidence of erosive arthritis (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.04-1.98). PD synovitis score was predictive of RRP at 1 year (OR 1.22, 95% CI 1.04-1.42). US erosions and PD synovitis scores were associated with change of SHS on linear regression. Of the 1,184 analyzed joints, 105 (8.9%) had radiographic erosion at 1 year. At the joint level, baseline US erosions were predictive of the presence of radiographic erosions at 1 year (P < 0.001). The same trend was observed in the joints without radiographic erosions at baseline (P = 0.052). CONCLUSION: US is useful to evaluate the potential severity of early arthritis: US erosions and PD-positive synovitis have prognostic value to predict future radiographic damage.

Factors associated with fatigue in early arthritis: results from a multicenter national French cohort study.

OBJECTIVE: Fatigue frequently occurs in patients with early arthritis (EA). Determinants of its severity are unknown. We aimed to identify the factors associated with fatigue in EA and changes in fatigue after 1 year of followup. METHODS: The Evaluation et Suivi de Polyarthrites Indifférenciées Récentes (Assessment and Followup of Early Undifferentiated Arthritis) cohort study is a multicenter, prospective, national cohort of patients with EA. At baseline and every 6 months up to 1 year, we recorded sociodemographic, clinical, and treatment characteristics, Arthritis Impact Measurement Scales 2 Short Form (AIMS2-SF) and Short Form 36 (SF-36) scores for health-related quality of life (HRQOL), and fatigue severity by a visual analog scale (f-VAS) and the SF-36 vitality score (fatigue_SF36). RESULTS: We included 813 patients (77% women, mean ± SD age 48 ± 13 years). At baseline, fatigue as assessed by the f-VAS or fatigue_SF36 was independently associated with young age, female sex, low education level, smoking, increased Disease Activity Score in 28 joints (DAS28), waking up at night, Sjögren's syndrome, and worse AIMS2-SF physical, affect, and symptom scores. At 1-year followup, a favorable change in fatigue scores was associated with increased baseline AIMS2-SF physical and affect scores (better quality of life), high baseline fatigue scores, and improved 1-year AIMS2-SF affect scores. Age, sex, and change in AIMS2-SF physical score, DAS28, and hemoglobin or C-reactive protein level were inconsistently associated with change in fatigue scores. The AIMS2-SF affect score explained most of the variance in baseline fatigue score and was an important factor in 1-year change in fatigue score. CONCLUSION: Fatigue in EA is multifactorial. Its level and its course are strongly associated with HRQOL, notably the affect dimension. These results should help professionals inform patients about fatigue, explore its causes, and develop tailored interventions.

Serum IgA rheumatoid factor and pyridinoline in very early arthritis as predictors of erosion(s) at two years: a simple model of prediction from a conservatively treated community-based inception cohort.

OBJECTIVE: To identify, in conservatively treated, very early arthritis patients, predictors of ≥1 erosion(s) at 2 years, and to construct a prediction model. METHODS: Community-based adults (n=310) who had never taken disease-modifying antirheumatic drugs (DMARDs) or steroids with swelling of ≥2 joints persisting for >4 weeks and lasting <6 months were recruited. Erosion status was assessed at 0, 6, 12, and 24 months; evaluations were comprised of clinical criteria (Disease Activity Score, Health Assessment Questionnaire), C-reactive protein level, erythrocyte sedimentation rate, autoantibodies, bone and cartilage markers, hand densitometry, and HLA class II shared epitopes. Patients meeting American College of Rheumatology rheumatoid arthritis (RA) criteria or with undifferentiated arthritis (UA) were followed and treated conservatively: one-third of RA patients and three-fourths of UA patients received no DMARDs during 2 years; a biologic agent was given to 1.8% of the patients during the first year. The main judgment criterion was ≥1 erosion(s) at 2 years. RESULTS: At 2 years, 219 patients were assessed; 31.3% with RA and 10.6% with UA had ≥1 erosion(s). Logistic regression analysis at that time showed erosion(s) strongly associated with serum IgA rheumatoid factor (IgA-RF) and pyridinoline levels for the 190 patients with no baseline erosions, with the corresponding receiver operating characteristic curve having an area under the curve of 0.77 (95% confidence interval 0.64-0.86). A prediction model was constructed with IgA-RF thresholds of 5 and 25 IU/ml and a pyridinoline threshold of 10 nM/liter; odds ratios ranged from 1 for IgA-RF<5 IU/ml and pyridinoline <10 nM/liter to 50.75 for the association of IgA-RF≥5 IU/ml and pyridinoline≥10 nM/liter. CONCLUSION: This model, using serum IgA-RF and pyridinoline concentrations, was able to predict≥1 erosion(s) at 2 years in very early arthritis patients.

CoRoT measures solar-like oscillations and granulation in stars hotter than the Sun.

Oscillations of the Sun have been used to understand its interior structure. The extension of similar studies to more distant stars has raised many difficulties despite the strong efforts of the international community over the past decades. The CoRoT (Convection Rotation and Planetary Transits) satellite, launched in December 2006, has now measured oscillations and the stellar granulation signature in three main sequence stars that are noticeably hotter than the sun. The oscillation amplitudes are about 1.5 times as large as those in the Sun; the stellar granulation is up to three times as high. The stellar amplitudes are about 25% below the theoretic values, providing a measurement of the nonadiabaticity of the process ruling the oscillations in the outer layers of the stars.

Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction.

OBJECTIVE: To investigate the involvement of angiogenesis markers in very early arthritis patients and their relevance to predict further joint destruction. METHODS: Levels of Vascular Endothelial Growth Factor (VEGF), angiopoietin-1 (Ang-1), and soluble Fms-like tyrosine kinase-1 (sFlt-1) were measured by ELISA in serum samples from 310 patients having polyarthritis, evolving for less than 6 months (VErA cohort). Each angiogenesis marker was measured at baseline and one year later. X-rays of hands and feet were carried out at inclusion and after 1 year and read using the van der Heidje-modified Sharp method. RESULTS: At baseline and after 1 year, VEGF levels were correlated with clinical and biological parameters of inflammation. We also observed a positive correlation between sFlt-1 levels and biological inflammation (Erythrocyte Sedimentation Rate (ESR): r=0.17, p=0.006; C Reactive Protein: r=0.14, p=0.02). Angiopoietin-1 levels were correlated with ESR (r=0.12, p=0.04). Interestingly, only VEGF levels measured at baseline were correlated with Disease Activity Score measured 1 year later. Relationship between angiogenesis markers and radiographic progression was also evaluated. VEGF and Ang-1 levels measured at inclusion were related with Sharp score after one year (VEGF: r=0.21, p<0.001; Ang-1: r=0.24, p<0.001; Spearman's test). Moreover, VEGF levels were higher in patients with radiographic progression (p=0.002). CONCLUSION: Serum concentrations of VEGF, sFlt-1 and angiopoietin-1 were correlated to parameters of inflammation and to bone destruction in early arthritis. These results contribute to demonstrate that angiogenesis reflects disease severity and angiogenesis markers might become a new useful tool to evaluate disease activity and to estimate outcome for patients with inflammatory arthritis.

Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis.

Tumour necrosis factor (TNF)-alpha plays a key role in the pathogenesis of rheumatoid arthritis (RA). It binds to two receptors, namely TNF receptor (TNFR)I and TNFRII. Several studies have suggested an association between TNFRII 196R/R genotype and RA. The objective of the present study was to evaluate the predictive value of the TNFRII 196R allele for RA diagnosis and prognosis in a cohort of patients with very early arthritis. We followed up a total of 278 patients recruited from the community, who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for less than 6 months, and who had not received disease-modifying antirheumatic drugs or steroid therapy. At 2 years, patients were classified according to the American College of Rheumatology criteria. All patients were genotyped with respect to TNFRII 196M/R polymorphism. Radiographs of hands and feet (read according to the modified Sharp method) and the Health Assessment Questionnaire were used to quantify structural and functional severity. The cohort of 278 patients was found to include 156 and 122 RA and non-RA patients, respectively. The TNFRII 196R allele was found to be associated with RA (P = 0.002). However, progression of radiographic severity and Health Assessment Questionnaire scores over 1 year did not differ between carriers of the 196R allele and noncarriers. Our findings suggest that the TNFRII 196R allele may be associated with RA diagnosis but that it does not predict early radiographic progression or functional severity in patients with very early, unclassified arthritis.