Jacqueline R. Chipping

The incidence of rheumatoid arthritis in the UK: comparisons using the 2010 ACR/EULAR classification criteria and the 1987 ACR classification criteria. Results from the Norfolk Arthritis Register

Objectives The development of new classification criteria for rheumatoid arthritis (RA) calls for a re-estimation of RA incidence rates. The objectives of this study were to estimate the age and sex-specific incidence rates (IR) of RA in Norfolk, England using the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism criteria, and to compare those with IRs estimated using the 1987 ACR criteria. Setting The Norfolk Arthritis Register (NOAR), a large primary care inception cohort of patients with inflammatory oligo- and polyarthritis (IP) aged ≥ 16. Methods All patients notified to NOAR from 1990-5 with symptom onset in 1990 were included. The former Norwich Health Authority population was the denominator. Age and sex specific IRs using 1987 and 2010 classification criteria were calculated at baseline visit, annually for the first 3 years and at 5 years. Results 260 patients were notified to NOAR with symptom onset in 1990 and without an alternative diagnosis. IRs applying the 2010 criteria at baseline were 54/100 000 for women and 25/100 000 for men. Age and sex-specific IRs using the 2010 classification criteria at baseline were similar to cumulative IRs applying the 1987 criteria up to 5 years. However, some patients only ever satisfied one set of criteria and a proportion of IA patients (20%) did not satisfy either criteria set over 5 years. Conclusions The 2010 criteria classify similar numbers of patients as having RA at baseline, as the 1987 criteria would have taken up to 5 years to identify.

Mortality Trends in Patients With Early Rheumatoid Arthritis Over 20 Years: Results From the Norfolk Arthritis Register

To examine mortality rates in UK patients with early rheumatoid arthritis (RA) from 1990–2011 and compare with population trends.

N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR)

Background We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac dysfunction, in an inception cohort with early inflammatory polyarthritis (IP) and assessed its association with disease phenotype, cardiovascular disease (CVD), all-cause and CVD related mortality. Methods Subjects with early IP were recruited to the Norfolk Arthritis Register from January 2000 to December 2008 and followed up to death or until March 2010 including any data from the national death register. The associations of baseline NT-pro-BNP with IP related factors and CVD were assessed by linear regression. Cox proportional hazards models examined the independent association of baseline NT-pro-BNP with all-cause and CVD mortality. Results We studied 960 early IP subjects; 163 (17%) had prior CVD. 373 (39%) patients had a baseline NT-pro-BNP levels ≥100 pg/ml. NT-pro-BNP was associated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. 92 (10%) IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (≥100 pg/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These findings were robust to adjustment for conventional CVD risk factors and prevalent CVD. Conclusions In early IP patients, elevated NT-pro-BNP is related to HAQ and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors. Further study is required to identify whether NT-pro-BNP may be clinically useful in targeting intensive interventions to IP patients at greatest risk of CVD.

Has the Severity of Rheumatoid Arthritis at Presentation Diminished Over Time

Objective. To examine the pattern of disease severity in patients with rheumatoid arthritis (RA) at presentation to the Norfolk Arthritis Register (NOAR) over 20 years. Methods. NOAR is a primary-care–based cohort of patients with recent-onset inflammatory polyarthritis. At baseline, subjects are assessed and examined by a research nurse. The Health Assessment Questionnaire (HAQ) is administered and the DAS28 (28-joint Disease Activity Score) is calculated. Information is collected on disease-modifying antirheumatic drug exposure. In this study, patients (symptom duration of < 2 years at baseline) were grouped into 4 cohorts (Cohort 1: 1990–1994; Cohort 2: 1995–1999; Cohort 3: 2000–2004; Cohort 4: 2005–2008). The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for RA were applied retrospectively at baseline. Regression analyses were used to examine whether calendar year of presentation to NOAR was associated with baseline HAQ and DAS28 scores. Potential confounders included age at symptom onset, sex, rheumatoid factor, and anticyclic citrullinated peptide antibody positivity. Results. A total of 1724 patients met the ACR/EULAR 2010 RA criteria at baseline. Unadjusted mean DAS28 scores decreased over time. Calendar year of presentation to NOAR was significantly associated with lower DAS28 scores over time [Y = 4.51 + (–0.56 × year) + (0.44 × year2)]. Although unadjusted median HAQ scores increased over time, calendar year of presentation to NOAR was not significantly associated with HAQ scores [Y = (1.1) + (0.023 × year) + (0.05 × year2)]. Similar results were observed in each subpopulation of patients. Conclusion. While baseline disease activity has lessened slightly over time, there has been no improvement in baseline levels of functional disability.

Learned helplessness predicts functional disability, pain and fatigue in patients with recent-onset inflammatory polyarthritis

Objectives. Cross-sectional studies have found that learned helplessness (LH) is associated with disease outcome in patients with RA. However, little is known about the longitudinal impact of LH. The aim of this study was to investigate whether LH is associated with future disease outcome (disability, pain and fatigue) and to investigate whether LH changes over time in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Methods. Patients included in this investigation had been recruited to the Norfolk Arthritis Register, a primary-care-based inception cohort. LH was measured at baseline as patients’ total score on the Rheumatology Attitudes Index (RAI). A total of 443 patients completed the HAQ and visual analogue scales of pain and fatigue at baseline and after 2 years of follow-up. Results. Greater feelings of LH at baseline were associated with higher HAQ scores at follow-up [difference in HAQ score per 1-point increase in RAI score (β-coefficient) 0.02; 95% CI 0.01, 0.04]. Greater baseline LH was also associated with more pain (β-coefficient 1.0; 95% CI 0.4, 1.5) and more fatigue (β-coefficient 1.0; 95% CI 0.2, 1.4) at follow-up. LH was highly changeable during follow-up, with 87% of patients showing any change and 50% improving. Conclusion. Baseline LH independently predicted disability, pain and fatigue at follow-up. Half of patients reported fewer feelings of helplessness after 2 years of follow-up, suggesting that LH may potentially be a modifiable risk factor for disease outcome in IP and a target for intervention.

Twenty-year outcome and association between early treatment and mortality and disability in an inception cohort of patients with rheumatoid arthritis: Results from the Norfolk Arthritis Register

To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease‐modifying antirheumatic drugs/steroids) and mortality and disability during follow‐up.

Predictors of and outcomes following orthopaedic joint surgery in patients with early rheumatoid arthritis followed for 20 years

Objectives To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. Methods Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. Results Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patients risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)]. Conclusion HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment.

Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register

Objective To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart. Methods Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression. Results In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI −23% to −10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24). Conclusion Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.

Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study

BackgroundOral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure.MethodsSubjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks.ResultsA total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort.ConclusionsRF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment.

OP0033 Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity, but not Their Concentration, Are Associated with Increased Mortality in Patients with Rheumatoid Arthritis: Results from Two Large Independent Cohorts

Background In patients with inflammatory arthritis, the autoantibodies rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) have been associated with poor outcomes such as increased disease activity, radiographic progression and disability. However, the utility of antibody level in predicting prognosis of inflammatory arthritis, in particular rheumatoid arthritis (RA), has not clearly been established. Objectives To investigate RF and ACPA status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA). Methods Data from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohort were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive as defined in the 2010 criteria, firstly by either RF or ACPA level, secondly by RF level alone and thirdly by ACPA level alone. Finally, patients were grouped as seronegative, single antibody positive or double antibody (RF and ACPA) positive. Cox regression models were applied to explore associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment. Results 4962 (NOAR: 3053, EAC: 1909) patients were included. 35% and 42% of patients were ACPA/RF positive in NOAR and EAC respectively. There were 787 deaths during 36 109 person years follow up in NOAR, and 275 deaths during 16 187 person years follow up in the EAC. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% CI): 1.35 (1.06-1.71) and 1.58 (1.16-2.15). Table 1 NOAR Leiden EAC HR* 95% CI HR* 95% CI RF/ACPA low positive vs negative 0.80 0.57–1.13 1.92 2 1.30–2.80 RF/ACPA high positive vs negative 1.44 1.21–1.70 1.42 1.06–1.91 RF low positive vs negative 0.80 0.59–1.07 1.62 1.16–2.26 RF high positive vs negative 1.49 1.23–1.80 1.63 1.19–2.24 ACPA low positive vs negative 1.39 1.00–1.93 2.21 1.31–3.72 ACPA high positive vs negative 1.32 1.06–1.64 1.25 0.93–1.69 Single positive vs negative 1.21 0.96–1.54 1.38 0.96–1.99 RF & ACPA positive vs negative 1.35 1.06–1.71 1.58 1.16–2.15 HR, hazard ratio; CI, confidence interval; RF, rheumatoid factor; ACPA, anti-citrullinated peptide antibodies; inflammatory marker = C-reactive protein in NOAR, = erythrocyte sedimentation rate in EAC. Both antibodies negative was used as reference group. *Adjusted for age at symptom onset, sex, baseline smoking status, year of inclusion in cohort & inflammatory marker. Conclusions Patients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4033