Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis:Results from the Norfolk Arthritis Register

Objectives: Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP.  Methods: Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5. Remission was defined as no tender or swollen joints (out of 51). Patients were classified as NR or PR, respectively, if they were in remission at: no assessment or ⩾3 consecutive assessments after baseline, and IR otherwise. Ordinal regression and a random effects model, respectively, were used to examine the association between baseline factors, remission group and HAQ scores over time.  Results: A total of 868 patients (66% female) were included. Of these, 54%, 34% and 12% achieved NR, IR and SR, respectively. In multivariate analysis, female sex (odds ratio, OR 0.47, 95% CI: 0.35, 0.63), higher tender joint count (OR = 0.94, 95% CI: 0.93, 0.96), higher HAQ (OR = 0.59, 95% CI: 0.48, 0.74), being obese (OR = 0.70, 95% CI: 0.50, 0.99), hypertensive (OR = 0.67, 95% CI: 0.50, 0.90) or depressed (OR = 0.74, 95% CI: 0.55, 1.00) at baseline were independent predictors of being in a lower remission group. IR and SR were associated with lower HAQ scores over time and lower DAS28 at year 5.  Conclusion: Women with higher tender joint count and disability at baseline, depression, obesity and hypertension were less likely to achieve remission. This information could help when stratifying patients for more aggressive therapy

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 1990-94 (Cohort 1 (C1)) and 2000-04 (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 (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 (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 ten years (95% CI -23% to -10%) whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared to C1 (all cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: SHR 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.<br/

How to develop, externally validate, and update multinomial prediction models

Multinomial prediction models (MPMs) have a range of potential applications across healthcare where the primary outcome of interest has multiple nominal or ordinal categories. However, the application of MPMs is scarce, which may be due to the added methodological complexities that they bring. This article provides a guide of how to develop, externally validate, and update MPMs. Using a previously developed and validated MPM for treatment outcomes in rheumatoid arthritis as an example, we outline guidance and recommendations for producing a clinical prediction model using multinomial logistic regression. This article is intended to supplement existing general guidance on prediction model research. This guide is split into three parts: 1) Outcome definition and variable selection, 2) Model development, and 3) Model evaluation (including performance assessment, internal and external validation, and model recalibration). We outline how to evaluate and interpret the predictive performance of MPMs. R code is provided. We recommend the application of MPMs in clinical settings where the prediction of a nominal polytomous outcome is of interest. Future methodological research could focus on MPM-specific considerations for variable selection and sample size criteria for external validation

Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se:a multicenter cohort study

BACKGROUND: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies. METHODS: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals without RA. Furthermore, RA patients fulfilling the 1987 criteria from three early arthritis cohorts from the Netherlands (n = 678), the United Kingdom (n = 761), and Sweden (n = 795) were used. Data on smoking, RF, anti-CCP2, and anti-CarP were available. A total score of autoantibodies was calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by logistic regression. RESULTS: In the population-based non-RA cohort, no association was found between smoking and one autoantibody (RF or anti-CCP2), but smoking was associated with double-autoantibody positivity (OR 2.95, 95% CI 1.32-6.58). In RA patients, there was no association between smoking and the presence of one autoantibody (OR 0.99, 95% CI 0.78-1.26), but smoking was associated with double-autoantibody positivity (OR 1.32, 95% CI 1.04-1.68) and triple-autoantibody positivity (OR 2.05, 95% CI 1.53-2.73). CONCLUSIONS: Smoking is associated with the concurrent presence of multiple RA-associated autoantibodies rather than just ACPA. This indicates that smoking is a risk factor for breaking tolerance to multiple autoantigens in RA

CD27(-)CD38(low)CD21(low) B-Cells Are Increased in Axial Spondyloarthritis

B-cells have received little attention in axial spondyloarthritis (axSpA) and for this reason their role in pathogenesis remains unclear. However, there are indications that B-cells may be involved in the disease process. Our objective was to obtain insights into the composition of the peripheral B-cell compartment of axSpA patients compared to healthy donors (HD) and patients with primary Sjögren’s syndrome (pSS), a typical B-cell-associated autoimmune disease. Special emphasis was given to CD27-negative B-cells expressing low levels of CD21 (CD21(low) B-cells), since this subset is implicated in autoimmune diseases with strong involvement of B-cells. Transitional B-cells (CD38(hi)) were excluded from the analysis of the CD27(-)CD21(low) B-cell compartment. This study included 45 axSpA patients, 20 pSS patients and 30 HDs. Intriguingly, compared to HDs the frequency of CD27(-)CD38(low)CD21(low) B-cells was significantly elevated in both axSpA and pSS patients (P<0.0001 for both comparisons). The frequency of CD27(-)CD38(low)CD21(low) B-cells expressing the activation-induced immune markers T-bet and CD11c was decreased in axSpA patients compared to HDs. A higher proportion of CD27(-)CD38(low)CD21(low) B-cells expressed the chemokine receptor CXCR3 in axSpA compared to HDs, suggestive for active involvement of these cells in an inflammatory process. The frequency of CD27(-)CD38(low)CD21(low) B-cells in axSpA patients correlated positively with age and erythrocyte sedimentation rate. Furthermore, axSpA patients with extra-skeletal manifestations (ESM) showed increased frequencies of CD27(-)CD38(low)CD21(low) B-cells compared to patients without ESM. In conclusion, our findings are suggestive of active B-cell involvement in the pathogenesis of axSpA, against prevailing dogma

Direct health costs of inflammatory polyarthritis 10 years after disease onset: Results from the Norfolk Arthritis Register

Objectives: To explore the change in direct medical costs associated with inflammatory polyarthritis (IP) 10 to 15 years after its onset. Methods: Patients from the Norfolk Arthritis Register who had previously participated in a health economic study in 1999 were traced 10 years later and invited to participate in a further prospective questionnaire-based study. The study was designed to identify direct medical costs and changes in health status over a 6-month period using previously validated questionnaires as the primary source of data. Results: A representative sample of 101 patients with IP from the 1999 cohort provided complete data over the 6-month period. The mean disease duration was 14 years (SD 2.1, median 13.6, interquartile range 12.6–15.4). The mean direct medical cost per patient over the 6-month period was £1496 for IP (inflated for 2013 prices). This compared with £582 (95% CI £355–£964) inflated to 2013 prices per patient with IP 10 years earlier in their disease. The increased cost was largely associated with the use of biologics in the rheumatoid arthritis subgroup of patients (51% of total costs incurred). Other direct cost components included primary care costs (11%), hospital outpatient (19%), day care (12%), and inpatient stay (4%). Conclusion: The direct healthcare costs associated with IP have more than doubled with increasing disease duration, largely as a result of the use of biologics. The results showed a shift in the direct health costs from inpatient to outpatient service use

Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register

Objective: The British Society for Rheumatology Biologics Register (BSRBR) has collected data on adverse events including pregnancies in patients with rheumatoid arthritis treated with anti-tumour necrosis factor (anti-TNF) therapy. The purpose of this report is to summarise the pregnancy outcomes in women treated with anti-TNF in the BSRBR. Methods: Patients were categorised according to anti-TNF exposure as follows: (1) exposure to anti-TNF and to methotrexate (MTX) and/or leflunomide (LEF) at conception (n=21 pregnancies); (2) exposure to anti-TNF at conception (n=50); (3) exposure to anti-TNF prior to conception (n=59); (4) no exposure to anti-TNF (control group; n=10). Results: Eighty-eight live births in a total of 130 pregnancies were reported in patients who received anti-TNF before or during pregnancy. The rate of spontaneous abortion was highest among patients exposed to anti-TNF at the time of conception (with MTX/LEF 33% and without MTX/LEF 24%). This compared with 17% spontaneous abortions in those with prior exposure to anti-TNF and 10% spontaneous abortions in the control group. Ten terminations were performed. Conclusion: Although the results to date have been promising, no firm conclusions can be drawn about the safety of anti-TNF during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception cannot yet be changed

Do associations between education and obesity vary depending on the measure of obesity used? A systematic literature review and meta-analysis

Background Consistent evidence suggests a relationship between lower educational attainment and total obesity defined using body mass index (BMI); however, a comparison of the relationships between educational attainment and total obesity (BMI ≥30 kg/m2) and central obesity (waist circumference (WC) > 102 cm for men and WC > 88 cm for women) has yet to be carried out. This systematic literature review (SLR) and meta-analyses aimed to understand whether i) the associations between education and obesity are different depending on the measures of obesity used (BMI and WC), and ii) to explore whether these relationships differ by gender and region. Methods Medline, Embase and Web of Science were searched to identify studies investigating the associations between education and total and central obesity among adults in the general population of countries in the Organisation for Economic Co-operation and Development (OECD). Meta-analyses and meta-regression were performed in a subset of comparable studies (n=36 studies; 724,992 participants). Results 86 eligible studies (78 cross-sectional and eight longitudinal) were identified. Among women, most studies reported an association between a lower education and total and central obesity. Among men, there was a weaker association between lower education and central than total obesity (OR central vs total obesity in men 0.79 (95% CI 0.60, 1.03)). The association between lower education and obesity was stronger in women compared with men (OR women vs men 1.66 (95% CI 1.32, 2.08)). The relationship between lower education and obesity was less strong in women from Northern than Southern Europe (OR Northern vs Southern Europe in women 0.37 (95% CI 0.27, 0.51)), but not among men. Conclusions Associations between education and obesity differ depending on whether total or central obesity is used among men, but not in women. These associations are stronger among women than men, particularly in Southern European countries