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Objective: The discovery of anti-citrullinated protein antibodies (ACPAs) and the introduction of new therapeutic options have had profound impacts on early rheumatoid arthritis (RA) care. Since ACPA status, most widely assessed as reactivity to cyclic citrullinated peptides (CCPs), influences treatment decisions in early RA, we aimed to determine whether anti-CCP remains a predictor of disease activity and radiographic joint damage in more recent 'real-world' early RA. Method: Two observational early RA cohorts from Sweden enrolled patients in 1996–1999 (TIRA-1, n = 239) and 2006–2009 (TIRA-2, n = 444). Clinical and radiographic data and ongoing treatment were prospectively collected up to 3 years. Two other cohorts served as confirmation cohorts (TRAM-1, with enrolment 1996–2000, n = 249; and TRAM-2, 2006–2011, n = 528). Baseline anti-CCP status was related to disease activity, pharmacotherapy, and radiographic joint damage according to Larsen score. Results: In the TIRA-1 cohort, anti-CCP-positive patients had significantly higher 28-joint Disease Activity Score, swollen joint count, C-reactive protein level, and erythrocyte sedimentation rate during follow-up compared with anti-CCP-negative patients. In TIRA-2, no such differences were found, but baseline anti-CCP positivity was associated with higher 3 year Larsen score (5.4 vs 3.5, p = 0.039). In TRAM-2, anti-CCP also predicted radiographic damage (8.9 vs 6.7, p = 0.027), with no significant differences in disease activity. Conclusion: In the early RA cohorts recruiting patients in 2006–2011, baseline anti-CCP positivity was not associated with disease activity over time, but was associated with increased radiographic damage at follow-up. Hence, close radiographic monitoring is warranted in early anti-CCP-positive RA regardless of disease activity. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular disease (CVD) is increased among patients with rheumatoid arthritis (RA). The underlying cause is not clear. In this prospective study, patients with early RA were investigated for associations between subclinical atherosclerosis and CVD risk factors as well as inflammation. Method: At diagnosis, RA patients were recruited into a prospective study. A subgroup was included (n = 55) for ultrasound measurements of intima-media thickness (IMT) at inclusion (T0), and after 5 years (T5) and 11 years (T11). Thirty-one age and gender-matched controls were also included for comparison. Results: IMT increased significantly between T0 and T11 among patients and controls (p < 0.0001). No statistically significant differences in IMT between patients and controls were detected at T11, T5, or T0 (p > 0.05 for all). In simple regression models, IMT at T11 was significantly associated with age (p < 0.0001), as well as systolic blood pressure at T0 (p < 0.01) and T11 (p < 0.01) among RA patients. Furthermore, the composite Systematic COronary Risk Evaluation (SCORE) measurements (p < 0.0001) and Reynolds risk score (p < 0.01) and the radiographic Larsen score (p < 0.05) at T0 were all significantly associated with IMT at T11. Results from conditional logistic regression analysis showed an increased progression rate between T0 and T11 in the RA group compared with controls (p < 0.05). Conclusion: We found increased atherosclerotic development among patients with RA compared with controls 11 years after diagnosis. The atherosclerotic burden was associated with disease severity at baseline. [ABSTRACT FROM AUTHOR]

Objective For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. Methods A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status. Results Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10−7); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression. Conclusion Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11. [ABSTRACT FROM AUTHOR]

The article discusses a study of rs12212067 minor allele in FOXO3A with respect to the severity of RA (rheumatoid arthritis) in multiple cohorts. Topics discussed include the Leiden Early Arthritis Clinic (EAC) cohort made up of 587 patients with early RA, the Umea cohort consisting of 459 patients with early RA from Sweden and the Wichita cohort consisting of 101 patients from a single practice in Wichita, Kansas and the notion FOXO3A is not a major factor that regulates the severity of RA.

Objective: To compare application of the 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for diagnosing rheumatoid arthritis (RA) in clinical practice. Method: The medical records of patients with early arthritis attending the Rheumatology Department, Umeå University Hospital (n = 1026) were analysed. Patients with synovitis in at least one joint, no diagnosis other than RA being better for explaining the synovitis, and duration of symptoms less than 1 year at first visit, and at least 1 year of follow-up were included consecutively. Fulfilment of the 1987 and 2010 criteria at baseline was evaluated. Sensitivity and specificity for each criterion set, where estimated by using the outcome measures: initiation of methotrexate (MTX) therapy during the first year, and a clinical diagnosis of RA at the 1-year follow-up. Radiographs of hands and feet were evaluated using the Larsen score. Results: The study included 313 patients, of whom 56% fulfilled the 1987 ACR criteria, 74% the 2010 ACR/EULAR criteria, and 53% both sets of criteria at baseline. The sensitivity/specificity for the 1987 and 2010 criteria with MTX within the first year as the outcome measure was 0.68/0.79 and 0.84/0.54, respectively, and with a diagnosis of RA at follow-up 0.72/0.83 and 0.91/0.65, respectively. Older patients (i.e. ≥ 60 years) more often fulfilled the 2010 criteria. Patients who fulfilled the 2010 ACR/EULAR but not the 1987 ACR criteria had a lower Larsen score at inclusion and after 2 years. Conclusions: Compared with the 1987 ACR criteria, the 2010 ACR/EULAR criteria have higher sensitivity but lower specificity, especially in patients aged ≥ 60 years. The 1987 ACR criteria are suggested to predict a more erosive disease. [ABSTRACT FROM AUTHOR]

Objectives: To study the influence of female hormonal factors on the development of rheumatoid arthritis (RA) in relation to the human leucocyte antigen (HLA)-DRB1 shared epitope (SE), the protein tyrosine phosphatase ( PTPN22) 1858T variant, anti-citrullinated protein antibodies (ACPAs), and immunoglobulin (Ig)M-rheumatoid factor (IgM-RF). Methods: A case-control study (1:4) was nested within the Medical Biobank of northern Sweden. Females who had subsequently developed RA (n = 70), median of 2.7 years before the onset of symptoms, and matched controls (n = 280) were identified from among the blood donors. A questionnaire concerning previous exposures until disease onset, including hormonal and reproductive factors, and smoking habits was distributed. Results: Breastfeeding was significantly associated with the development of RA [odds ratio (OR) 4.8, 95% confidence interval (CI) 1.43-15.8]. Increasing time of breastfeeding increased the risk of RA (OR 5.7, 95% CI 1.83-17.95) for breastfeeding ≥ 17 months. In a multiple logistic regression analysis, increasing time of breastfeeding (OR 9.5, 95% CI 2.14-42.43 for ≥ 17 months), seropositivity for ACPAs (OR 19.5, 95% CI 4.47-84.81), and carriage of the PTPN22 1858T variant (OR 3.2, 95% CI 1.36-7.54) remained significant predictors of RA. Users of oral contraceptives (OC) for ≥ 7 years had a decreased risk for development of RA (OR 0.37, 95% CI 0.15-0.93). Conclusions: A longer duration of breastfeeding increased the risk of developing RA, especially among individuals seropositive for ACPA or IgM-RF or carrying the PTPN22 1858T variant. Use of OC for ≥ 7 years was associated with a decreased risk. [ABSTRACT FROM AUTHOR]