Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts.

OBJECTIVE: Patients with rheumatoid arthritis (RA)-related autoantibodies have an increased mortality rate. Different autoantibodies are frequently co-occurring and it is unclear which autoantibodies associate with increased mortality. In addition, association with different causes of death is thus far unexplored. Both questions were addressed in three early RA populations. METHODS: 2331 patients with early RA included in Better Anti-Rheumatic Farmaco-Therapy cohort (BARFOT) (n=805), Norfolk Arthritis Register (NOAR) (n=678) and Leiden Early Arthritis Clinic cohort (EAC) (n=848) were studied. The presence of anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and anticarbamylated protein (anti-CarP) antibodies was studied in relation to all-cause and cause-specific mortality, obtained from national death registers. Cox proportional hazards regression models (adjusted for age, sex, smoking and inclusion year) were constructed per cohort; data were combined in inverse-weighted meta-analyses. RESULTS: During 26 300 person-years of observation, 29% of BARFOT patients, 30% of NOAR and 18% of EAC patients died, corresponding to mortality rates of 24.9, 21.0 and 20.8 per 1000 person-years. The HR for all-cause mortality (95% CI) was 1.48 (1.22 to 1.79) for ACPA, 1.47 (1.22 to 1.78) for RF and 1.33 (1.11 to 1.60) for anti-CarP. When including all three antibodies in one model, RF was associated with all-cause mortality independent of other autoantibodies, HR 1.30 (1.04 to 1.63). When subsequently stratifying for death cause, ACPA positivity associated with increased cardiovascular death, HR 1.52 (1.04 to 2.21), and RF with increased neoplasm-related death, HR 1.64 (1.02 to 2.62), and respiratory disease-related death, HR 1.71 (1.01 to 2.88). CONCLUSIONS: The presence of RF in patients with RA associates with an increased overall mortality rate. Cause-specific mortality rates differed between autoantibodies: ACPA associates with increased cardiovascular death and RF with death related to neoplasm and respiratory disease.

Association of morbid obesity with disability in early inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: Obesity has been associated with disease outcomes in inflammatory arthritis. This study aimed to investigate cross-sectionally the relationship between body mass index (BMI) and functional disability in a large inception cohort of patients with early inflammatory polyarthritis (IP). METHODS: Patients age ≥16 years with ≥2 swollen joints for ≥4 weeks were recruited into the Norfolk Arthritis Register. At the initial assessment, clinical and demographic data were obtained, joints were examined, and height and weight were measured. Blood samples were taken to measure inflammatory markers and autoantibodies, and patients completed the Health Assessment Questionnaire (HAQ) to assess functional disability. Univariate and multivariate ordinal regression were used to examine the cross-sectional association between BMI and the HAQ. Multiple imputation using chained equations allowed inclusion of patients with missing variables. RESULTS: A total of 1,246 patients were studied (median age 57 years). Of those patients, 782 patients (63%) were female and 303 (25%) were obese (BMI ≥30 kg/m(2) ). Morbid obesity (BMI ≥35 kg/m(2) ) was significantly associated with worse functional disability in the univariate and multivariate analysis with missing data imputed, adjusting for age, sex, symptom duration, smoking status, disease activity, autoantibodies, comorbidities, and treatment (multivariate odds ratio 1.87, 95% confidence interval 1.14-3.07). CONCLUSION: Morbid obesity in patients with early IP is associated with worse HAQ scores. This should be taken into account in patient management and when interpreting the HAQ in clinical practice.

Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register.

OBJECTIVE: To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). METHODS: 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. RESULTS: 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16-35). Parous women had significantly lower HAQ scores over time than nulliparous women (-0.19, 95% CI -0.32 to -0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. CONCLUSION: Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.

Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy.

OBJECTIVE: To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset. METHODS: Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery. RESULTS: 27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses. CONCLUSION: Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.