Early Rheumatoid Arthritis Network Research Articles

Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.

To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (β=0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (β=0.24 [95% CI 0.14, 0.34]), less exercise (β=0.17 [95% CI 0.09-0.25]), and less education (β = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.

P198 The role of comorbidities alongside patient and disease characteristics on long-term disease activity in RA using UK inception cohort data

Abstract Background/Aims Control of disease activity in Rheumatoid Arthritis (RA) is crucial to prevent long-term joint damage and disability. European Alliance of Associations for Rheumatology (EULAR) guidelines recommend focus on disease activity when measuring health outcomes in people living with RA. Particularly, one of their four overarching principles targets clinical remission, defined as the absence of significant inflammatory disease activity, or low disease activity an acceptable alternative. In EULAR’s most recent guidelines (2014), attention was drawn to the role of comorbidities in RA disease management noting the “potential to preclude treatment intensification”. Besides this, recent work by the EULAR Task Force on difficult-to-treat RA recognises that comorbidities can influence the assessment of inflammatory activity in individuals with RA. This study aimed to identify early predictors of poor disease activity at five and 10 years, focussing on comorbidities alongside clinical/sociodemographic factors at first presentation. Methods Patients were recruited from two UK-based RA cohorts; Early Rheumatoid Arthritis Study (ERAS, 1986-2001) and Early Rheumatoid Arthritis Network (ERAN, 2002-2012). Participants were classified into two groups; low (<3.2) and moderate/high (≥3.2) Disease Activity Score (DAS28) at 5/10 years. Clinical information (e.g., rheumatoid nodules, erosions), sociodemographic factors (e.g., ethnicity, deprivation) and comorbidity burden (measured using the Rheumatic Diseases Comorbidity Index [RDCI]) were recorded at baseline and yearly thereafter. Multivariable logistic regression models (outcome; low versus DAS28≥3.2) were fitted using multiple imputation. Results 2,701 patients with RA were recruited (mean age 56.1 years, 66.9% female); 5-year follow-up data were available for 1,718 (63.4%) and 10-year for 820 (30.4%) patients. A higher proportion of individuals had DAS28≥3.2 values at 10 years than five (65.6% vs 59.7%). In multivariable analyses, baseline RDCI was not associated with DAS28 at five (OR 1.05, 95% CI 0.91 to 1.22) or 10 years (OR 0.99, 95% CI 0.75 to 1.31). Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ were associated with DAS28≥3.2 at both timepoints, with no association found with age at onset. Being seropositive was associated with DAS28≥3.2 at 5 but not 10 years of follow-up. Conversely, a relationship existed between presence of erosions at baseline and 10-year DAS28 (OR 1.82, 95% CI 1.16 to 2.85). Conclusion This study found no association between baseline comorbidity burden and long-term RA disease activity. However, in models adjusted for comorbidity burden, associations with sociodemographic and clinical factors were demonstrated. These results build upon those relating to functional outcome and will accelerate the identification of those RA patients at increased risk of worse outcomes at initial rheumatology appointment. Additionally, these findings suggest that tailored intervention can be implemented in a timely manner, in line with national and international recommendations, potentially limiting permanent joint damage and disability to improve quality of life for individuals with RA. Disclosure A.D. Busby: None. J. Wason: None. A.G. Pratt: None. A. Young: None. J. Isaacs: None. E. Nikiphorou: None.

Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis.

To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.

Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network.

ObjectivesFatigue is a disabling symptom in people with RA. This study aims to describe the prevalence, risk factors and longitudinal course of fatigue in early RA.MethodsDemographic, clinical, quality of life (QoL), comorbidities and laboratory data were from the Early RA Network (ERAN), a UK multicentre inception cohort of people with RA. Fatigue was measured using the vitality subscale of the 36-item Short Form Health Survey, where higher values represent better QoL. Baseline prevalences of fatigue classifications were age and sex standardized. Linear regression, hierarchical growth curve modelling and group-based trajectory modelling (GBTM) were utilized.ResultsAt baseline (n = 1236, 67% female, mean age 57 years), the mean vitality was 41 (s.d. 11) and disease duration was 11 months (interquartile range 7–18). Age- and sex-standardized prevalence rates of fatigue and severe fatigue were 44% (95% CI 39, 50) and 19% (95% CI 15, 23), respectively. Fatigue changed little over 3 years and five measurement occasions β = −0.13 (95% CI −0.23, −0.02). GBTM identified two subgroups, which we named ‘Fatigue’ (53%) and ‘No-fatigue’ (47%). Female sex, worse pain, mental health and functional ability were associated with greater fatigue and predicted Fatigue group membership (area under the receiver operating characteristics curve = 0.81). Objective measures of inflammation—swollen joint count and ESR—were not significantly associated with fatigue.ConclusionsFatigue is prevalent and persistent in early RA. Diverse characteristics indicative of central mechanisms are associated with persistent fatigue. Management of fatigue might require interventions targeted at central mechanisms in addition to inflammatory disease modification. People who require such interventions might be identified at presentation with early RA.

THU0100 FATIGUE: A PREVALENT AND PERSISTENT SYMPTOM IN EARLY RHEUMATOID ATHRITIS

Background:Fatigue is associated with poor quality of life in people with Rheumatoid Arthritis (RA). The exact burden of fatigue in RA is uncertain. Evidence shows that fatigue may persist, even in people with well-controlled inflammatory disease. However, this is largely based on cross sectional data, and data from people with long standing or refractory disease. This study aims to examine the nature of fatigue in early RA.Objectives:Describe the prevalence of fatigue and longitudinal course of fatigueInvestigate heterogeneity in the course of fatigue and identify risk factors associated with fatigue heterogeneityMethods:Data were from the early Rheumatoid Arthritis Network (ERAN), an inception cohort of people with a disease duration of &lt;24mths, recruited from 2002-11 (n=1236). ERAN collected demographic, clinical, quality of life, comorbidities and laboratory data at baseline, 3-6 mths, and then annually.Fatigue was measured using the Vitality subscale of the Short Form Health Survey questionnaire (SF36VT). Fatigue and severe fatigue were classified as SF36VT values lower than 1 and 2 standard deviations (SD) below the UK healthy population average respectively. Baseline prevalence rates standardized to Eurostat 2013 by age and sex were calculated.The course of fatigue was examined using linear mixed effect models. Group Based Trajectory Modelling (GBTM) was used to examine heterogeneity in the course of fatigue. Baseline characteristics were then used to identify predictors of group membership using univariate and multiple regression analysis.Results:Baseline characteristics include female sex (67%), mean age = 57(SD±14) yrs. Mean SF36VT score = 41(SD±11), median disease duration was 11 mths (IQR:7 – 18).The age and sex standardized prevalence rates of fatigue and severe fatigue were 44%(CI:38-50) and 18% (CI:15 – 22) respectively.729 (59%) participants were included in the longitudinal analysis. Over the course 4 years follow up, and after accounting for the effect of age, sex, patient’s global assessment of disease activity, BMI, pain and mental health, there was a reduction in the population vitality levels from baseline,(β: -0.14CI: -0.26 to -0.02, p ≤ 0.001). Inflammation measured by erythrocyte sedimentation rate (ESR) was not significantly associated with the course of fatigue.GBTM analysis identified 2 sub-groups. These groups were named ‘Fatigue’ and ‘No-fatigue’ groups and comprised about 52% and 47% of the population respectively (Fig 1).Females, participants with, at baseline, higher BMI, higher disability score (HAQ), disease activity score (DAS28), worse pain, mental health scores and higher comorbidity score (RDCI) were more likely to belong to the Fatigue group (each p ≤ 0.05) in univariate analysis. However, higher BMI (OR 1.05 (CI: 1.0 – 1.1), HAQ (OR 2: CI: 1.5 - 2.7), RDCI(OR 1.3, CI: 1.2 – 1.5), worse SF36 pain and mental health scores (OR 0.93 CI: 0.92 – 0.95) and (OR 0.97, CI: 0.95 – 0.99) were collectively associated with fatigue group membership (AUROC=0.81).Fig 1.Fatigue TrajectoriesConclusion:Fatigue is a prevalent symptom in RA, even in early disease. Embedded within the RA population are distinct sub-populations, with or without fatigue. Those with fatigue at baseline were likely to continue to report fatigue over 4 years of follow up. Unlike our previous data on pain trajectories within this cohort, a ‘resolving fatigue’ was not found. Diverse baseline characteristics, including pain, were associated with persistent fatigue. Management of fatigue might require strategies additional to disease modification, and people who require such interventions might be identified at presentation with early RA.Disclosure of Interests:Onosi Ifesemen: None declared, Daniel McWilliams Grant/research support from: Grant support from Pfizer Ltd, Adam Young: None declared, Patrick Kiely: None declared, David Walsh Grant/research support from: Grant support from Pfizer Ltd and Eli Lilly, Consultant of: Consultancy to Eli Lilly, Pfizer, Abbvie and GSK (all payments made to University of Nottingham). Consultancy to Love Productions(all payments made to the University of Nottingham).

Secular changes in the progression of clinical markers and patient-reported outcomes in early rheumatoid arthritis

ObjectivesTo examine secular trends in the progression of clinical and patient-reported outcomes in early RA.MethodsA total of 2701 patients recruited to the Early Rheumatoid Arthritis Study or Early Rheumatoid Arthritis Network with year of diagnosis from 1986 to 2011. The 5-year progression rates for patients diagnosed at different points in time were modelled using mixed-effects regression; 1990, 2002 and 2010, were compared. Clinical markers of disease included the 28-joint count DAS and the ESR. Patient-reported markers included the HAQ, visual analogue scale of pain and global health, and the Short-Form 36.ResultsStatistically significant improvements in both 28-joint count DAS and ESR were seen over the 5 years in patients diagnosed with RA compared with those diagnosed earlier. By 5 years, 59% of patients with diagnosis in 2010 were estimated to reach low disease activity compared with 48% with diagnosis in 2002 and 32% with diagnosis in 1990. Whilst HAQ demonstrated statistically significant improvements, these improvements were small, with similar proportions of patients achieving HAQ scores of ≤1.0 by 5 years with a diagnosis in 1990 compared with 2010. Levels of the visual analogue scale and the Mental Component Scores of the Short-Form 36 indicated similar, statistically non-significant levels over the 5 years, irrespective of year diagnosed.ConclusionThis study demonstrates improvements in inflammatory markers over time in early RA, in line with improved treatment strategies. These have not translated into similar improvements in patient-reported outcomes relating to either physical or mental health.

Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

BackgroundRA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities.MethodsPeople from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups.ResultsDAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode.ConclusionFlares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.

Remission vs low disease activity: function, quality of life and structural outcomes in the Early Rheumatoid Arthritis Study and Network.

ObjectivesTo examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA.MethodsDemographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6–3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit.ResultsOf 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3–5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points).ConclusionThese findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.

Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts

ObjectivesTo assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.DesignMulticentre prospective early RA inception...

Discrete Trajectories of Resolving and Persistent Pain in People With Rheumatoid Arthritis Despite Undergoing Treatment for Inflammation: Results From Three UK Cohorts

Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation. Growth mixture modelling was used to identify discrete trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics (n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years. The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout 3 years of follow-up of >1 standard deviation worse than the UK general population average. Discrete persistent pain (59–79% of cohort participants) and resolving pain (19–27%) trajectories were identified in each cohort. In Early RA Network, a third trajectory displaying persistently low pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent pain trajectory. When trajectories were compared, greater disability (adjusted odds ratio = 2.3–2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (adjusted odds ratio = 1.6–1.8) were risk factors for persistent pain trajectories in each cohort. In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during treatment for RA. Inflammation does not fully explain the pain trajectories, and noninflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long-term burden of arthritis pain. PerspectiveImmunosuppression decreases inflammation in RA, but pain outcomes are less favorable. Discrete persistent and resolving pain trajectories were identified after treatment, both in early and established RA. Smoking and greater disability at baseline predicted persistent pain. Identifying patient subgroups with a poor pain prognosis could enable adjunctive treatment to improve outcomes.

The association of obesity with disease activity, functional ability and quality of life in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Study/Early Rheumatoid Arthritis Network UK prospective cohorts.

To examine associations between BMI and disease activity, functional ability and quality of life in RA. Data from two consecutive, similarly designed UK multicentre RA inception cohorts were used: the Early RA Study (ERAS) and the Early RA Network (ERAN). Recruitment figures/median follow-up for the ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years), respectively. Standard demographic and clinical variables were recorded at baseline and annually. Multilevel piecewise longitudinal models with a change point at 2 years were used with the 28-joint DAS (DAS28), ESR, HAQ and 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) components as dependent variables. BMI was examined in separate models as both continuous and categorical variables (based on World Health Organization definitions) and up to 5 years from disease onset. BMI data from 2386 newly diagnosed RA patients (11 348 measures) showed an increase in BMI of 0.27 U annually (95% CI 0.21, 0.33). Baseline obesity was associated with a significant reduction in the odds of achieving a low year 2 DAS28 [OR 0.52 (95% CI 0.41, 0.650)]. At year 2, HAQ and SF-36 PCS scores were significantly worse but not at year 5 in patients obese at baseline. Obesity at year 2 was associated with higher DAS28 scores at year 2, but not at year 5, and also associated with significantly higher HAQ and SF-36 PCS scores at years 2 and 5. Obesity prevalence is rising in early RA and associates with worse disease activity, function and health-related quality of life, with a significant negative impact on achieving a low DAS28. The data argue strongly for obesity management to become central to treatment strategies in RA.

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity.Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants (1) commencing anti-TNF therapy (n = 10,813), or (2) changing between non-biologic DMARDs (n = 2992), (3) Early Rheumatoid Arthritis Network participants (n = 813), and (4) participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n = 45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation.DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components.DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment.

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data.

BackgroundRheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs.MethodsData were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined.ResultsFive, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline.ConclusionsDiscordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and activity. These findings could be used to identify a sizeable subgroup of people with RA who might gain added benefit from pain management strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1186-8) contains supplementary material, which is available to authorized users.

Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States.

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease-modifying antirheumatic drug treatment. A total of 2,701 patients were recruited over 25 years to 2 UK-based RA inception cohorts: the Early Rheumatoid Arthritis Study (9 centers; 1986-2001) and the Early Rheumatoid Arthritis Network (23 centers; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed-effects models, including random effects for recruitment center. Age at onset increased from 53.2 to 57.7 years in 1990 and 2010, respectively (2.6 months/year; 95% confidence interval [95% CI] 1.2, 4.1). Sex ratio, the proportion living in deprived areas, and smoking status were unchanged (P > 0.05) and there were no changes in the proportion seropositive or erosive at baseline (P > 0.05). After controlling for treatment at the time of assessment, erythrocyte sedimentation rate decreased and hemoglobin increased over time (P > 0.05); however, the Health Assessment Questionnaire (HAQ), the Disease Activity Score (DAS), the DAS in 28 joints, and joint counts were unchanged (P > 0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions, including hypertension. There was a significant increase in body mass index (0.15 units/year; 95% CI 0.11, 0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010. Age at onset and comorbidity burden, especially obesity, have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast, there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity, or HAQ at presentation. Treatment strategies in early RA should take greater account of the impact of comorbidity on outcomes.

Erosive and osteoarthritic structural progression in early rheumatoid arthritis.

To investigate factors associated with joint damage in early RA, and how comorbid OA might influence patient assessment and outcomes. Baseline radiographs of hands and feet from 512 participants in the Early RA Network cohort, and after 3 (±1) years, 166 of those participants yielded complete scores for RA [erosions, joint space narrowing (JSN)] and OA [JSN, osteophytes (OST)] using validated atlases. DAS28-P is the proportion of DAS28 attributed to patient-reported factors. Adjusted odds ratios were calculated using logistic regression. OA was common at baseline in early RA (40% hand and 48% foot) and associated with RA radiographic score. Higher baseline RA scores were associated with increasing age and ESR, and lower DAS28-P. OST scores were associated with higher age. DAS28 and patient-reported outcomes improved, whereas RA and OA radiographic scores deteriorated by follow-up. Erosive progression was predicted by higher baseline erosions, female gender, better mental health and lower DAS28-P. Hand OST progression was predicted by baseline OST scores. Inflammatory disease activity was associated with erosive, but not with OA progression. Baseline hand OA predicted worse physical function at follow-up, but radiographic progression did not explain changes in patient-reported outcomes. OA is a common comorbidity that might confound radiographic and clinical assessment, but does not fully explain erosive progression or patient-reported outcomes in early RA. Early RA management should address psychosocial factors and comorbidities, as well as joint inflammation.

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

ObjectivesTo examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes.MethodsHealth Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA...

The Effect of Disease Severity and Comorbidity on Length of Stay for Orthopedic Surgery in Rheumatoid Arthritis: Results from 2 UK Inception Cohorts, 1986-2012.

To examine factors predicting length of stay (LoS) for orthopedic intervention in rheumatoid arthritis (RA). LoS for orthopedic intervention was examined in 2 consecutive, multicenter inception cohorts: the Early RA Study (n = 1465, 9 centers) and the Early RA Network (n = 1236, 23 centers). Date, type of orthopedic procedure, and LoS were recorded and validated against national data, the UK National Joint Registry, and the UK Hospital Episode Statistics database. Clinical, laboratory, and radiographic measures and comorbidity recorded at baseline and annually were examined for their predictive power on LoS using regression analysis. A total of 770 of 2701 patients (28.5%) had 1602 orthopedic interventions: 40% major (mainly total hip/knee replacements), 24% intermediate (mainly hand/wrist and ankle/foot surgery), and 16% minor (mainly soft tissue surgery). Median (interquartile range) LoS was 8 (5-13), 3 (1-5), and 1 (0-2) days for major, intermediate, and minor interventions, respectively. Older age predicted longer LoS (p < 0.001) whereas a more recent operation year predicted shorter LoS (p < 0.001). Markers of active disease, namely low hemoglobin, high Health Assessment Questionnaire, and high Disease Activity Scores in the first year all predicted longer LoS for all types of surgery (p = 0.001, p < 0.001, p = 0.05, respectively). Presence of 1 or more major comorbidities predicted longer LoS (p < 0.001). Comorbidity and standard clinical and laboratory markers of disease activity affect the LoS for orthopedic surgery in RA, which has important clinical and economic implications, providing a target for improving patient outcomes.

THU0248 Three-Year Sustained Remission in Early RA: Predictors and Structural Outcomes. Analysis of Longitudinal Observational Data in Two Multicentre UK Inception Cohorts over 25 Years

BackgroundAchieving sustained remission in Rheumatoid Arthritis (RA) is more important than achieving point remission, albeit more challenging, and likely to have greater impact on long-term outcomes of disease such as...

OP0127 Impact of Disease Activity and Treatment on Progression of Functional Limitation in RA

BackgroundFunctional limitation is a key outcome in rheumatoid arthritis and a key driver of the cost of RA in health economic models. Due to restrictive inclusion/exclusion criteria and short follow...