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Objectives To examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA. Methods Demographic, 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) Results Of 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 Conclusion These findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.

Background: Giant cell arteritis is the commonest form of medium-to-large vessel vasculitis, requiring long-term corticosteroid therapy. The short- and long-term side effects of corticosteroids are many, including weight gain, psychological effects, osteoporosis, cardiometabolic complications, and infections. Materials and Methods: Various agents used in place of or in combination with corticosteroids to reduce corticosteroid-related side effects were reviewed. However, considerable variation in practice was identified giving unclear guidance. This review included the most recent evidence on methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide, abatacept, and tocilizumab Results and Discussion: Also discussed are encouraging results with tocilizumab in GCA patients. Amongst the agents available for steroid-sparing effects, tocilizumab demonstrated the most robust data and is consequently recommended as the agent of choice for steroid-sparing, for remission induction, remission maintenance, and treating relapsing and refractory cases of GCA.

The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28. Electronic supplementary material The online version of this article (10.1007/s00296-018-4184-0) contains supplementary material, which is available to authorized users.

Objectives To examine associations between BMI and disease activity, functional ability and quality of life in RA. Methods 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. Results 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. Conclusion 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.

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; P0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P0.001). 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; P0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P0.001). 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; P0.001), 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.

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 cohort studies; the early RA study (ERAS) and the early RA network (ERAN).SettingSecondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.ParticipantsPatients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3–6 months, at 12 months and annually thereafter.Primary and secondary outcome measuresPrimary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.ResultsOf 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.ConclusionsMTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.

Objective: To examine secular trends in demographic, clinical manifestations and comorbidity on first presentation of RA prior to DMARD treatment. Methods: 2701 patients were recruited over 25years to two UK-based RA inception cohorts: the Early RA Study (9 centres; 1986-2001) and the Early RA Network (23 centres; 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 centre. Results: Age-at-onset increased from 53.2 to 57.7 years in 1990 and 2010 respectively (2.6 months/year; 95% CI 1.2-4.1). Gender-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, ESR reduced and haemoglobin increased over time (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 BMI (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. Conclusions: 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 co-morbidity on outcomes. This article is protected by copyright. All rights reserved.

Objective. To evaluate, firstly, all published data on baseline and annual progression rates of radiographic damage from all longitudinal observational cohorts, and secondly, the association of standard clinical and laboratory parameters with long-term radiographic joint damage. Methods. A comprehensive search of the literature from 1975 to 2014, using PubMed, SCOPUS and Cochrane databases, identified a total of 28 studies that investigated long-term radiographic progression, and 41 studies investigating predictors of long-term radiographic progression. This was submitted and approved by PROSPERO in February 2014 (Registration Number: CRD42014007589). Results. Meta-analysis indicated an overall baseline rate of 2.02%, and a yearly increase of 1.08% of maximum damage. Stratified analysis found that baseline radiographic scores did not differ significantly between cohorts recruiting patients pre- and post-1990 (2.01% vs 2.03%; P > 0.01); however, the annual rate of progression was significantly reduced in the post-1990 cohorts (0.68% vs 1.50%; P < 0.05). High levels of acute phase markers, baseline radiographic damage, anti-CCP and RF positivity remain consistently predictive of long-term radiographic joint damage. Conclusion. Critical changes in treatment practices over the last three decades are likely to explain the reduction in the long-term progression of structural joint damage. Acute phase markers and presence of RF/anti-CCP are strongly associated with increased radiographic progression.

Background Treat-to-target (T2T) principles in rheumatoid arthritis (RA) are now widely recognised as effective in achieving optimal disease outcomes. Objectives To examine for differences in outcomes between low (LDAS) and remission (RDAS) disease activity score (DAS) categories, addressing the question: is LDAS a ‘good enough’ treatment target in RA? Methods Data from two consecutive UK multi-centre RA inception cohorts with similar design were used: the Early RA Study (ERAS) and Early RA Network (ERAN). Recruitment figures/median follow up for 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 then annually until the end of study follow up. Disease activity was categorised by mean DAS28 score between years 1–5 as remission [mRDAS Results Out of 2701 patients, 468 (17%) were in mRDAS, 284 (11%) in mLDAS in the first five years of disease. Lower proportions had achieved sRDAS (8%), sLDAS (6%) and Boolean (2%) remission. Mean age was similar across categories; more women were in low vs remission DAS. Compared to mLDAS or sLDAS, inflammatory markers, DAS, functional (HAQ, PCS) and mental (MCS) scores tended to be better in the mRDAs, sRDAS or Boolean remission categories (figure 1). Significant differences (p Conclusions The results demonstrate striking differences between remission and low DAS categories, suggesting worse functional and SF36 outcomes over time in the low DAS categories. This supports that remission should be the primary T2T goal in in RA. Disclosure of Interest None declared

Background The treat-to-target (T2T) approach, with earlier, aggressive treatment has resulted in improvements in rheumatoid arthritis (RA) outcomes 1,2 . Whether these improvements have translated into improvements in patient reported outcomes is less clear. Studies have indicated declines in pain and function as well as depression and anxiety. However, these studies are limited to short follow-up periods or were restricted to cross-sectional, rather than longitudinal analyses. Objectives To assess changes in 5 year progression rates for disease activity and patient reported outcomes in a prospective cohort of early RA patients between 2002 and 2011. Methods The Early RA Network (ERAN) is a longitudinal prospective cohort study that recruited 1236 early RA patients from 2002 to 2011. DAS-28 and SF-36 were measured at baseline, 6 months, 12 months and then yearly. Multi-level linear regression were used to model 5 year progression rates of both DAS-28 and SF-36 in patients recruited between 2002–2011. Models controlled for sex and age and seropostivity at baseline. DMARD use at baseline was controlled for using propensity score weighting. Year of diagnosis was entered as a continuous variable, allowing for the mean of the outcome variables to be estimated for 2002 and 2011. Restricted cubic splines were used to account for non-linear progression over time. Results Disease activity for patients diagnosed in 2011 demonstrated a statistically significant decrease at year 5 compared to patients diagnosed in 2002 (5 year estimated mean difference −0.35; 95% CI 0.22–0.49, p 0.05). Mental health was similar to the normalised population mean of 50, irrespective of year diagnosed. However, levels of vitality/fatigue, function and pain remain less favourable for all early RA patients over the first 5 years. Conclusions Although disease activity has shown a marked decline at 5 years between 2002 and 2011, there is little evidence that this has led to improvements of an equivalent magnitude in function, pain, fatigue and mental health. Treatment should also focus on improved function, pain management, fatigue and mental health as part of the T2T protocol. References [1] Twigg S, et al. Fatigue, older age, higher body mass index and female gender predict worse disability in early rheumatoid arthritis despite treatment to target: A comparison of two observational cohort studies from the United Kingdom. Arthritis Care Res. (Hoboken). 2017. doi:10.1002/acr.23281 [2] Carpenter L, et al. Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution from Rheumatoid Factor in Two Multicenter UK Inception Cohorts. Arthritis Care Res. 2017;69. Disclosure of Interest None declared

Background Early, intensive treatment to achieve remission, or at least low disease target (Treat-to-Target, T2T), is advocated to prevent and/or reduce structural joint damage and disability in early Rheumatoid Arthritis (RA). A recent study shows how patients with moderate disease exhibit similar rates of functional disability and orthopaedic surgical interventions to those patients with high disease1. To our knowledge, no study has looked at longitudinal observational data to investigate the progression of structural joint damage in these patient sub-groups. Objectives To investigate the long-term progression of radiographic joint damage in patients with sustained moderate disease activity. Methods Demographic, clinical, laboratory and radiographic data from the Early Rheumatoid Arthritis Study (ERAS) was available for 1,465 patients. Radiographic damage was scored using the modified Sharp/van der Heijde (SvdH) method. The original three variable 44 joint count Disease Activity Score (DAS-44) was used. Mean DAS-44 over the first 5 years was estimated for patients with at least two DAS-44 scores. Patients were stratified based on EULARs thresholds of low ( 3.7) disease. Mixed-effects negative binomial regression modelled patients9 radiographic progression over 5 years, whilst controlling for key confounders, including age at onset, sex, rheumatoid factor status and baseline functional disability. Results A total of 1,110 patients with 3,751 observations over the 5 year period (mean =3.4 observations per patient) were analysed. 396 (36%), 363 (33%) and 351 (32%) patients were classified in the low, moderate and high DAS-44 groups respectively. The low group had lower SvdH scores at 1 year compared to the moderate group (12.9 vs. 19.2, p Conclusions Sustained moderate disease over the first five years of RA indicates similar levels of radiographic progression compared to sustained high disease. This study provides support on the importance of tight treatment control with early and aggressive therapy according to T2T principles. Preventing sustained moderate disease activity states can help reduce radiographic progression and consequently joint destruction, minimising the risk of disability in the long-term. References Nikiphorou, E. et al. 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. Ann. Rheum. Dis. annrheumdis–2015–208669 (2016). Disclosure of Interest L. Carpenter Grant/research support from: NIHR Programme Grant, S. Norton: None declared, E. Nikiphorou: None declared, K. Jayakumar: None declared, D. McWilliams: None declared, J. Dixey: None declared, P. Kiely: None declared, D. Walsh: None declared, A. Young: None declared

The structural damage caused by rheumatoid arthritis (RA) can often be mitigated by orthopaedic surgery in late disease. This study evaluates the value of predictive factors for orthopaedic intervention. A systematic review of literature was undertaken to identify papers describing predictive factors for orthopaedic surgery in RA. Manuscripts were selected if they met inclusion criteria of cohort study design, diagnosis of RA, follow-up duration/disease duration ≥3 years, any orthopaedic surgical interventions recorded, and then summarised for predictive factors. A separate predictive analysis was performed on two consecutive UK Early RA cohorts, linked to national datasets. The literature search identified 15 reports examining predictive factors for orthopaedic intervention, 4 inception, 5 prospective and 6 retrospective. Despite considerable variation, acute phase, x-ray scores, women and genotyping were the most commonly reported prognostic markers. The current predictive analysis included 1602 procedures performed in 711 patients (25-year cumulative incidence 26%). Earlier recruitment year, erosions and lower haemoglobin predicted both intermediate and major surgery (P

Objective To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup. Methods The study examined orthopedic data from the UK Early RA Study (1986–1999, 9 centers; n = 1,465) and the UK Early RA Network (2002–2012, 23 centers; n = 1,236) with linkage to national data sets (Hospital Episode Statistics, National Joint Registry, and Office of National Statistics). Clinical and laboratory measures and hand and foot radiographs were standardized and obtained yearly in both cohorts. The use of disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologic therapies reflected the contemporary conventional practices and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, and interventions were classified into major, intermediate, and minor categories. Results A total of 1,602 orthopedic surgical procedures were performed in 770 patients (29%) over a maximum of 25 years of followup. The 25-year cumulative incidence rate of major interventions was 21.7% (range 19.4–24.0%), and that of intermediate interventions was 21.5% (range 17.8–25.5%). There was a decline in the 10-year cumulative incidence of intermediate surgeries over time (P < 0.001), but not of major/minor surgery. This decline coincided with a gradual shift from sequential monotherapy to combination DMARD therapies and biologic agents in recent recruitment periods. Conclusion Orthopedic surgery is an important and common outcome in RA. Only the rates of hand/foot surgery showed a consistent decline from 1986 to 2011. Possible explanations include differences in the pathophysiologic processes affecting the joints, variations in the responses to therapy between large-joint and small-joint destructive processes, and changes in service provision and thresholds for surgery over time.

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.

Objective.The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques.Methods.Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR).Results.The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016).Conclusion.The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.

Objectives To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6–3.2), low-moderate (LMDAS≥3.2–4.19), high-moderate (HMDAS 4.2–5.1) and high (HDAS>5.1). Results Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.

Objective.To examine factors predicting length of stay (LoS) for orthopedic intervention in rheumatoid arthritis (RA).Methods.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.Results.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).Conclusion.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.

OBJECTIVES: The aims of the present rheumatoid arthritis (RA) study were (1) to examine the levels of serum 3-B-3 and 7-D-4 to find out whether they are different from controls, (2) to find out whether the concentrations of these epitopes change with disease duration in early RA and (3) whether the serum concentrations of 3-B-3 and 7-D-4 in early RA are prognostic for subsequent disease progression. METHODS: The concentrations of 3-B-3 and 7-D-4 in sera were quantitated by immunoassays. RESULTS: The levels of 3-B-3 and 7-D-4 were significantly lower in RA than in controls (3- to 30-fold, P < 0.001). Changes in 3-B-3 and 7-D-4 were apparent with disease duration. At first presentation, the 3-B-3 concentration was lowest and increased at 12 months (3-fold, P < 0.001). This increase was transient since by 24 and 36 months the concentrations were not different to those at first presentation. The level of 7-D-4 was also lowest when the patients first presented at clinic and increased with time at 6 months (2-fold, P < 0.001). The increase was more prolonged for 7-D-4, remaining elevated at 12, 24 and 36 months. The lack of correlations of serum 3-B-3 and 7-D-4 with clinical measurements showed that these markers were not prognostic for disease severity. CONCLUSIONS: The levels of 3-B-3 and 7-D-4 differed between RA and control sera, and changed with disease duration. These markers were not prognostic in predicting disease outcome.

Objective. This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. Methods. Between 1986 and 1998, 1460 patients with RA symptoms

To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup.The study examined orthopedic data from the UK Early RA Study (1986-1999, 9 centers; n = 1,465) and the UK Early RA Network (2002-2012, 23 centers; n = 1,236) with linkage to national data sets (Hospital Episode Statistics, National Joint Registry, and Office of National Statistics). Clinical and laboratory measures and hand and foot radiographs were standardized and obtained yearly in both cohorts. The use of disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologic therapies reflected the contemporary conventional practices and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, and interventions were classified into major, intermediate, and minor categories.A total of 1,602 orthopedic surgical procedures were performed in 770 patients (29%) over a maximum of 25 years of followup. The 25-year cumulative incidence rate of major interventions was 21.7% (range 19.4-24.0%), and that of intermediate interventions was 21.5% (range 17.8-25.5%). There was a decline in the 10-year cumulative incidence of intermediate surgeries over time (P0.001), but not of major/minor surgery. This decline coincided with a gradual shift from sequential monotherapy to combination DMARD therapies and biologic agents in recent recruitment periods.Orthopedic surgery is an important and common outcome in RA. Only the rates of hand/foot surgery showed a consistent decline from 1986 to 2011. Possible explanations include differences in the pathophysiologic processes affecting the joints, variations in the responses to therapy between large-joint and small-joint destructive processes, and changes in service provision and thresholds for surgery over time.

Objectives. To study the prevalence at diagnosis and cumulative incidence of comorbidity in RA, associations with clinical features and impact on outcome. Methods. Standard clinical, laboratory and radiological measures of RA, and details of comorbidity and extra-articular features were recorded at baseline and yearly in an inception cohort of 1460 patients with recently diagnosed RA from nine regions in the UK. The General Practice Research Database was used to compare the incidence of common comorbid conditions (International Classification for Disease-10 codes). Results. Baseline prevalence was 31.6% and 8.6% for all comorbidities and extra-articular features, respectively, and 15-year cumulative incidence was 81% and 53%, respectively. Rates of hypertension [standardized incidence ratio (SIR) = 1.61; 95% CI 1.43, 1.79] and ischaemic heart disease (SIR = 1.60; 95% CI 1.35, 1.84) were raised compared with figures for the general population, as was stroke in females (SIR = 1.34; 95% CI 1.02, 1.77) and chronic obstructive pulmonary disorder in males (SIR = 1.63; 95% CI 1.17, 2.26). Comorbidity was associated with risk of both all-cause and cardiovascular mortality (hazard ratio = 1.09; 95% CI 1.02, 1.17) and increased rates of functional decline over 10 years (b = 0.011; 95% CI 0.004, 0.019). Comorbidity was not related to disease activity or structural damage. Conclusion. Significant comorbidity was present at the outset of RA, increasing with follow-up, mainly in cardiovascular, non-cardiac vascular and respiratory systems. Specific conditions (e.g. hypertension) occurred more frequently than in the general population. Comorbidity was related to mortality and functional decline, and more intensive therapies may need consideration in these patients. As many co-existent conditions are amenable to preventative/therapeutic measures, comorbidity needs earlier detection and management in order to reduce its impact on outcome in RA.

Objective. To explore rates of and reasons for work disability in an early RA cohort with median 10 years follow-up. Methods. One thousand four hundred and sixty patients with early RA (

In England and Wales, the National Institute for Health and Clinical Excellence (NICE) has provided guidance [technology appraisals (TAs) 130, 186, 195, 198 and 225] on the use of biologic drugs for the treatment of RA. This is based on an analysis of efficacy, safety and cost-effectiveness, and has resulted in a complex management pathway that restricts freedom to prescribe biologics according to their licensed indications. Specifically, TNF antagonists are the only class of biologics that can be used first line in DMARD-inadequate responders, and only in patients with a persistent 28-joint DAS score of ≥5.1. Alternative biologic agents are denied to those with contraindications to anti-TNF drugs and are also not supported following intolerance to TNF antagonists. Rituximab is the only class of biologic permitted after TNF antagonist inefficacy, in the absence of a contraindication to its use, whereas abatacept and tocilizumab are licensed and may be a more efficacious choice at this stage in some patient groups. Furthermore, for patients who demonstrate sequential inadequate responses, treatment is restricted to one TNF antagonist, rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event. In this review, we discuss the treatment algorithm published by NICE, and suggest alternatives where perceived deficiencies exist.

The Standards, Audit and Guidelines Working Group (SAGWG) of the British Society for Rheumatology (BSR) have recently updated the guidelines on eligibility for anti-TNF drugs in RA [1] and have updated the anti-TNF safety and efficacy guidelines [2] for general use of the rheumatology community. The National Institute for Heath and Clinical Excellence (NICE) in the UK, which is the is an independent organization responsible for providing national guidance in the UK on promoting good health and preventing and treating ill health, has published a technology appraisal guidance [3] for use of rituximab in RA in 2007. Furthermore, a consensus statement from EULAR [4] was also published in 2007. Therefore, it was felt appropriate to undertake a review of the currently available data as new evidence was available. The group did not wish to duplicate the guidance in those documents, but wished to review the more recent evidence and supplement what is already known.

Objectives; To describe conservative and surgical foot care in patients with RA in England and explore factors that predict the type of foot care received. Methods; Use of podiatry and type of foot surgery were outcomes recorded in an inception cohort involving nine rheumatology centres that recruited patients with RA between 1986 and 1998 across England. Associations between patient-specific factors and service use were identified using univariate logistic regression analyses. The independence of these associations was then verified through multiple binary logistic regression modelling. Results; Data were collected on 1237 patients with RA [66.9% females, mean (S.D.) age at disease onset = 54.36 (14.18) years, median DAS = 4.09 (1st quartile = 3.04, 3rd quartile = 5.26), median HAQ = 1 (0.50, 1.63)]. Interventions involving the feet in the cohort were low with only 364 (30%) out of 1218 receiving podiatry and 47 (4%) out of 1237 patients having surgery. At baseline, female gender, increasing age at onset, being RF positive and higher DAS scores were each independently associated with increased odds of seeing a podiatrist. Gender, age of onset and baseline DAS were independently associated with the odds of having foot surgery. Conclusions; Despite the known high prevalence of foot pathologies in RA, only one-third of this cohort accessed podiatry. While older females were more likely to access podiatry care and younger patients surgery, the majority of the RA population did not access any foot care.

Practice Based Commissioning (PBC) and Payment by Results (PBR) have introduced perverse incentives for clinicians to work in ways that are not always in the best interests of the patient. PBC may lead to patients who would benefit from a specialist opinion not being referred on cost-saving grounds

Objectives. To evaluate the strengths and weaknesses of a register of management and outcomes of recently diagnosed RA, and allow comparisons between rheumatology centres on good clinical practice and guidelines. Methods. A register of newly diagnosed RA was initiated in 1986 in nine different regions of England, later expanded to UK-wide membership in 2002. Standardized data collection includes disease activity, function, radiological damage, therapy, hospitalizations, major comorbidity and mortality. A centralized database generates individual reports and comparative data for each centre yearly. Aims have been compared with actual achievements and any changes over 25 years. Results. Thirty rheumatology centres have recruited 2866 patients. Study outputs have included peer-reviewed scientific publications and contributions to the recent National Audit Office report on RA. Referral times into secondary care have changed little over 25 years, but time to initiation of drug therapies has decreased. Delays between publication of clinical trial evidence and management guidelines and their implementation in normal clinical practice are illustrated by relatively infrequent use of combination therapies at diagnosis. Consecutive case recruitment, centre participation and follow-up were reportedly compromised by local funding issues. Centre participants report a benefit from feedback of actual clinical practice compared with recommended standards of care. Conclusions. Most of the original objectives have been achieved. Cohort studies based predominantly in District General Hospitals provide unique insights into the natural history and impact of RA, its management, the translation of research findings into clinical practice and provide participating centres with important clinical governance and professional development opportunities.

Inhibitors of TNF-a represent important treatment advances for a number of inflammatory conditions, including RA. TNF-a inhibitors offer a targeted strategy that contrasts with the non-specific immunosuppressive agents traditionally used to treat most forms of systemic inflammation. Information on who benefits from these agents and on their adverse effects continues to be collected through clinical studies, case series and reports and through national registries. In 2001 and 2005, the British Society for Rheumatology (BSR) established and updated guidelines for the use of anti-TNF drugs in RA [1, 2]. These guidelines have indicated which adult patients with RA should be eligible for treatment with anti-TNF therapies, precautions that need to be taken in their use and action that should be taken in the event of adverse effects. The previous guidelines applied to the then-available anti-TNF therapies {etanercept and infliximab in 2001 [1], and etanercept, infliximab and adalimumab (first-generation anti-TNF agents) in 2005 [2]}. Due to the large volume of information now available on these agents the BSR has, in 2010, produced separate guidelines on eligibility for anti-TNF treatment in RA (in press) These current guidelines cover the safety aspects of anti-TNF treatment in RA and apply to the first-generation products but also to the newly licensed second-generation anti-TNF drugs, certolizumab pegol and golimumab. There are relatively little safety data specifically for these second-generation agents but there are no data thus far to suggest that their side-effect profile would differ significantly from the first-generation agents. This is a rapidly changing field with new data emerging each month, so it is vital that clinicians keep up to date with this area of practice. These guidelines have Rheumatology Department, Royal Derby Hospital, Derby, Rheumatology Unit, Queen Alexandra Hospital, Portsmouth, Rheumatology Department, Nuffield Orthopaedic Centre, Oxford, Rheumatology Department, Poole Hospital, Poole, ARC Epidemiology Unit, University of Manchester, Manchester, Rheumatology Department, St George’s Healthcare, London, Rheumatology Department, Royal Lancaster Infirmary, Lancaster, Rheumatology Department, St Helens Hospital, St Helens, National Rheumatoid Arthritis Society, Maidenhead, Rheumatology Department, Addenbrooke’s Hospital, Cambridge, Rheumatology Department, Trafford General Hospital, Manchester, Rheumatology Unit, Worthing and Southlands NHS Trust, Worthing and Rheumatology Department, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.

Chris Deighton1, Kimme Hyrich2, Tina Ding1, Jo Ledingham3, Mark Lunt2, Raashid Luqmani4, Patrick Kiely5, Marwan Bukhari6, Rikki Abernethy7, Andrew Ostor8, Ailsa Bosworth9, Kate Gadsby1, Frank McKenna10, Diana Finney11 and Josh Dixey12, on behalf of BSR Clinical Affairs Committee & Standards, Audit and Guidelines Working Group and the BHPR 1Rheumatology Department, Royal Derby Hospital, Derby; 2ARC Epidemiology Unit, University of Manchester, Manchester; 3Rheumatology Unit, Queen Alexandra Hospital, Portsmouth; 4Rheumatology Department, Nuffi eld Orthopaedic Centre, Oxford; 5Rheumatology Department, St George’s Healthcare, London; 6Rheumatology Department, Royal Lancaster Infi rmary, Lancaster; 7Rheumatology Department, St Helens Hospital, St Helens; 8Rheumatology Department, Addenbrooke’s Hospital, Cambridge; 9National Rheumatoid Arthritis Society, Maidenhead; 10Department of Rheumatology, Trafford General Hospital, Manchester; 11Rheumatology Unit, Worthing and Southlands NHS Trust, Worthing; 12Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK

Total hip replacement has shown good outcomes for patients with rheumatoid arthritis. Can hip resurfacing give similar results for patients with rheumatoid arthritis? Using an international hip resurfacing register, 47 patients with rheumatoid arthritis were identified and age and gender matched to a group of 131 randomly selected patients with osteoarthritis of the hip joint. Patients completed a questionnaire to record function and implant revision. Hierarchical regression, Cox regression and Kaplan-Meier method were used for analysis. There was a significant increase in post operative hip score in both groups (p < 0.001) with rheumatoid group scoring higher as compared to the osteoarthritis group (p = 0.23). The post operative score was not significantly influenced by pre-operative score and age (p = 0.15 and 0.84, respectively) but the pre-operative score was a predictor of implant failure (p = 0.02). Patient mobility was affected by age with younger patients scoring high on mobility as compared to older patients (p = 0.01). The Kaplan-Meier analysis showed a survival rate of 96.3% in the rheumatoid group and 97.8% in the osteoarthritis group. This difference was not significant (Log rank test, p = 0.45). Our results from an independent and international register show that hip resurfacing provides good post-operative hip function and excellent implant survival for patients with rheumatoid arthritis of the hip joint. This procedure can be considered as a viable option for management of rheumatoid arthritis of the hip joint.

Objectives Pulmonary complications of RA are well described. Although some are benign, interstitial lung disease (ILD) has a poor prognosis. Few RA inception cohorts have reported the natural history of ILD related to RA (RA-ILD). We examine its incidence, outcome and prognostic indicators. Methods Extra-articular features and comorbidity have been recorded yearly in a well-established inception cohort of RA with a 20-year follow-up. Standard clinical, laboratory and radiological measures of RA were recorded at baseline and yearly. Details of deaths were provided by a national central register. Results Out of 1460 patients, 52 developed RA-ILD, half either at baseline or within 3 years of onset. The annualized incidence was 4.1/1000 (95% CI 3.0, 5.4) and the 15-year cumulative incidence 62.9/1000 (95% CI 43.0, 91.7). Incidence of RA-ILD was associated with older age, raised baseline ESR and HAQ. Evidence to implicate any drug effect (e.g. MTX) was lacking. Of these patients, 39 died, attributed to RA-ILD in 28. Median survival following diagnosis of RA-ILD was 3 years. Conclusions RA-ILD is an important and early feature of RA. It is related to disease activity and has a poor prognosis. Further studies are required to determine whether screening for pulmonary disease would identify these patients at an earlier stage.

Familial predisposition to chondrocalcinosis (CC) due to calcium pyrophosphate dihydrate (CPPD) crystal deposition is described in five English kindreds. Two families were characterized by premature-onset polyarticular CC with little associated structural arthropathy. In one of these families, recurrent childhood fits were strongly associated with subsequent development of CC. Affected members of the other three families resembled sporadic disease in showing predominantly late-onset, oligoarticular CC with mild arthritis and destructive change in only one case. Knee synovial fluid levels of inorganic pyrophosphate (PPi) and nucleoside triphosphate pyrophosphate (NTPP) did not differ from those of 59 sporadic cases of CC due to CPPD, although PPi and NTPP levels in both groups were higher than in normal knee synovial fluid (P less than 0.0001). Urinary PPi levels were not different from normal controls. Screening for other metabolic abnormality was negative in all cases. This is the first report of familial CC in the UK, and the first to associate this condition with childhood fits. Absence of overt primary abnormality of PPi metabolism suggests that other factors relating to crystal nucleation/growth may be more relevant to predisposition in these cases.

Objective. To determine how Larsen scores from digitized X-rays compare to those from film originals. Methods. A hundred sets of radiographs of patients recruited with early rheumatoid arthritis (RA) were assessed using the Larsen scoring system. Digitized copies of these sets were then viewed on a computer screen and scored according to Larsen in a random order. The quality of the digitized image was also recorded. For each set of X-rays, the signed difference between the score from film and the score from the digitized images was calculated. Results. A total of 95% of the digitized X-ray sets were scored successfully; 5% were not scored due to the images being unreadable. The mean difference between the two sets of scores was -1.2 (95% CI [-2.06, -0.37]). There was no trend in the difference with respect to the mean of the two scores (P > 0.1). Conclusion. The Larsen scoring of digitized X-ray images has been validated.

Background Sustained high disease activity in RA is known to result in worse outcomes. However, many patients remain in moderate disease activity states, yet their outcomes, are less well studied. Objectives To examine orthopaedic surgery as a surrogate marker of joint failure in patients who remain at different moderate disease activity levels in the first 5 years from disease-onset. Methods The Early RA Study (ERAS, n=1465, 1986-1999) and the Early RA Network (ERAN, n=1236, 2002-2012) collected standard clinical, radiological and laboratory measures yearly for a maximum (median) 25 (10) and 10 (3) years respectively. Clinical databases were validated with national sources: the National Joint Registry, Hospital Episode Statistics & National Death Register. Treatment regimens followed guidelines of the era, mainly conventional DMARDs & latterly biologics. Joint interventions were categorized into major (large joint replacements), intermediate (mainly synovectomies & arthroplasties of wrist/hand, hind/forefoot) or minor (mainly soft tissue). Mean DAS28 was calculated for each patient from year1 (after treatment-onset) to 5 and categorized into either remission [RemDAS ≤2.6], low [LowDAS >2.6 -3.2], low moderate [LowModDAS= >3.2-4.19], high moderate [HighModDAS 4.2-5.1] or high DAS [HighDAS >5.1]. Results A total of 2044 (76%) patients had at least two DAS28 recorded between year 1-5: 21% in RemDAS, 15% in LowDAS, 26% in LowModDAS, 21% in HighModDAS, 18% in HighDAS categories. The table shows that on moving from remission through to low/moderate/high states there was a progressive worsening in baseline clinical & laboratory variables. In multivariate Cox regression models controlling for age at disease onset, gender, recruitment year, symptom duration, baseline rheumatoid factor, BMI, HAQ, erosions and Haemoglobin, HighModDAS (HR 1.80, 95%CI 1.05-3.11, p=0.034) and HighDAS (HR 2.59, 95%CI 1.49-4.52, p=0.001) predicted higher risk for intermediate surgery, unlike LowModDAS or LowDAS categories. In the case of major joint surgery, LowModDAS (HR 2.07, 95%CI 1.28-3.33), HighModDAS (HR 2.16, 95%CI 1.32-3.52) and HighDAS (HR 2.48, 95%CI 1.50-4.11) all predicted an increasing risk (p Conclusions Patients who remain in low or high moderate disease activity levels in the first 5 years of disease, despite conventional DMARD therapy, have similar risks for joint failure and surgery as those with persistently high DAS. This is highly relevant in health systems where restrictions exist in the use of biologic DMARDs, which are based on DAS cut-offs and exclude moderate RA. Disclosure of Interest None declared

Background Comorbidities in Rheumatoid Arthritis (RA) can have a negative impact on functional ability. However, the extent of this impact is less well understood, especially in established disease. In the absence of a standardised and validated tool for comorbidity data collection, understanding which comorbidities at the early stages of disease have the greatest impact on functional outcomes is important in terms of preserving functional status and optimising disease management. Objectives To examine the effect of comorbidities by the first year of RA on 10-year functional status using the health assessment questionnaire (HAQ). Methods Data from two multi-centre (n=32) UK inception cohorts (1986-2013), the Early RA Study and Early RA Network (total n=2701) were used. DMARD-naive patients were recruited at presentation and standard clinical, laboratory and radiographic variables recorded at baseline and yearly thereafter. Date and cause of death was provided by the Medical Research Information Service. The presence of comorbidities and extra-articular manifestations was recorded at individual disease level. These were grouped into the standard ICD10 systems (n=15) and further subdivided by severity, e.g. cardiovascular major (ischaemic heart disease, cardiac failure) or minor (benign cardiac arrhythmias). Multivariate Cox regression analysis adjusting for age at disease onset, gender, baseline HAQ, BMI and presence of rheumatoid factor and recruitment year was used, with HAQ as the outcome at year 10. HAQ was examined as a binary outcome using the median HAQ at 10 years (1.13) as the cut-off since HAQ distribution did not allow for it to be treated as continuous in linear or generalized linear models. Results Of the patients with HAQ scores available at year 10, 189 and 99 patients had at least one major and one minor comorbidity respectively recorded by the first year of disease (1yr prevalence: 26.3% and 13.8%). Higher HAQ at 10yrs was significantly predicted in separate models by major respiratory comorbidities (HR 1.29, 95% CI 0.99-1.66, p=0.05) and major spinal disease (HR 2.03, 95%CI 1.08-3.09, p=0.026). Major respiratory disease included bronchiectasis and chronic obstructive pulmonary disease (COPD) and major spinal disease included C-spine subluxation, spinal stenosis and slipped disc disease with neurological compromise. At individual disease level, COPD was found to be the only significantly predictive comorbidity for higher HAQ at 10yrs (HR 1.48, 95% CI 1.08-2.01; p=0.013). Conclusions Co-existent major respiratory and spinal diseases are significant predictors of functional status at 10yrs from disease-onset in RA. At individual disease level, COPD predicted higher HAQ at 10yrs, highlighting its impact together with conventional measures of RA severity on functional status. Targeting and closely managing these conditions is therefore important in terms of long-term functional outcomes in RA. Acknowledgements We are indebted to all the nurses and rheumatologists from both cohorts for their participation and contribution to the study. Disclosure of Interest None declared

Background Comorbidity and extra-articular disease screening in Rheumatoid Arthritis (RA) is important as they impact negatively on disease outcomes and survival. Most RA observational studies have used generic indices such as the Charlson Comorbidity Index, or a simple comorbidity count. There is still no standardised, uncomplicated and validated instrument for collecting comorbidity data, relevant to contemporary and routine rheumatology practice. Objectives To examine the predictive value of comorbidities & extra-articular manifestations by the first year of RA on 10-year mortality. Methods The study was based on two multicentre (n=32) UK inception cohorts: the Early RA Study (1986-1999;n=1465) & Early RA Network (2002-2013;n=1236). Standard clinical, laboratory & radiographic variables were recorded at baseline & yearly intervals. Date/cause of death was provided by the Medical Research Information Service. The presence of comorbidities & extra-articular manifestations were grouped into the standard ICD10 systems (n=15) & further subdivided by severity, e.g. cardiovascular major (ischaemic heart disease [IHD], cardiac failure) or minor (benign cardiac arrhythmias). Multivariate Cox regression analysis adjusting for age at disease onset, gender, baseline BMI & presence of rheumatoid factor & recruitment year was used, with all-cause mortality as the outcome at 10 years. Results 896 (33%) patients with RA had at least one major comorbidity; 472 had at least one minor recorded by the first year of disease (1yr prevalence of major/minor comorbidities=35%/18.5%). There were 849 (31%) deaths (total number person-years=34048). The commonest comorbidities recorded were hypertension (1yr prevalence =15.7%), diabetes & thyroid disease (9.7%), IHD (5.1%). Significant predictors of 10yr mortality by disease system are shown in the table. Examination at individual disease level revealed that IHD, chronic obstructive pulmonary disease (COPD) & renal/urological malignancies significantly predicted 10yr mortality when tested separately & together in multivariate models: renal/urological malignancies HR 2.34; COPD HR 2.28; IHD HR 1.71, all p Conclusions Different comorbidities showed different predictive value for mortality in RA, with predominance seen with malignant disease. The best predictive model for 10yr mortality is the one that controlled for COPD, IHD and renal/urological malignancy, aside from standard demographic/patient variables. Further work is currently underway to develop a weighted comorbidity index based on these findings to be validated in the present & other cohorts. Disclosure of Interest None declared

Objective. To examine the cause of death in a large UK inception cohort of rheumatoid arthritis (RA), and whether this was related to disease duration and severity, treatment effects or extra-articular features and complications of RA. Methods. Standard clinical, laboratory, radiological and socio-economic measures were recorded at baseline and yearly in an inception cohort started in nine centres in 1986. Date and the cause of death were based on death certificates and the comparisons made with age and sex matched population figures. Risk factors for mortality were identified from baseline measures of disease. Results. There were 459 deaths (32%) in 1429 patients followed for up to 18 yrs. Standard mortality ratio was 1.27. Survival was significantly lower in the first 7 yrs of RA. Excess mortality was seen in cardiovascular disease (31%), pulmonary fibrosis (4%) and lymphoma (2.3%). Baseline predictors for mortality were men, older age, poor function, lower socio-economic status, extra-articular features, comorbidity, rheumatoid factor, X-ray erosions, high-ESR and low-haemoglobin. Conclusion. There was a modest increase in mortality in RA, mainly in the first 7 yrs. Deaths from cardiovascular disease and pulmonary fibrosis were higher than expected, but treatment-related deaths were low. Risk factors included less favourable socio-economic status, markers of disease severity and diminished function within the first year.

To construct a prognostic algorithm to predict 5-year functional outcome in rheumatoid arthritis (RA), based on the Health Assessment Questionnaire (HAQ).Data from all patients with 5-year followup (n = 985) were used from an inception cohort, the Early Rheumatoid Arthritis Study (ERAS). Possibly relevant prognostic factors considered in the initial stage of the model-building process were standard clinical, radiological, and laboratory features measured at baseline and at 1 year. Multivariate analysis was performed using logistic regression, and the predictive performance of the model was tested using measures of discrimination and calibration.Bootstrap resampling identified 6 variables that consistently predicted severe functional outcome. Functional grade III/IV (odds ratio 6.7) and HAQ at 1 year (odds ratio 2.4) were the most important. Other variables included socioeconomic status, hemoglobin, and radiographic and disease activity scores. Estimates of the regression coefficients and performance were corrected for over-fitting. Reasonably large values for the c-index (0.82) and the Nagelkerke R(2) (0.39) indicate that the set of prognostic factors explains the variation in outcome to a degree that implies good prediction for individual patients.The algorithm identifies patients in the first year of RA who are likely to have poor function by 5 years and who could potentially benefit from aggressive drug therapy. A nomogram is produced for simple application of the model in clinical practice. While further external validation is necessary, this model could allow clinicians to target aggressive therapy earlier in a patient's disease course.

We describe the pattern of early childhood seizures within a family with autosomal dominant chondrocalcinosis (CCAL, which causes adult-onset arthritis). All affected family members with CCAL experienced seizures in early childhood, usually, but not always, associated with fever. Similarities exist to the syndrome of generalized epilepsy with febrile seizures plus (GEFS+). A mutation within the ANKH gene on chromosome 5p has been found previously in this family; other patients with familial CCAL (but without seizures) have mutations in the same gene. ANKH codes for a transmembrane protein involved in the regulation of extracellular pyrophosphate ion levels, although its precise mechanism of action remains unclear. It is highly expressed in the brain, and its expression may be influenced by seizure activity. The mutation within this family creates a premature initiation codon, adding four amino acids to the N-terminus of the protein. We postulate that this may lead to a gain of function, causing seizure susceptibility as well as chondrocalcinosis. Mutations within this gene may underlie other forms of genetic epilepsy and febrile seizures.

OBJECTIVES: To assess the occurrence of and predictive factors for orthopaedic surgery in an inception cohort of rheumatoid arthritis (RA) patients recruited and followed prospectively for 5 yr in nine regions in England. METHODS: Standard clinical, laboratory and radiological assessments and all interventions were recorded at baseline and yearly in RA patients (less than 2 yrs symptoms) prior to the use of disease-modifying drugs. RESULTS: One thousand and sixty-four patients completed 5 yr of follow-up. Two hundred and sixty-four orthopaedic procedures for RA were performed in 181 (17%) patients at a median of 36.5 months from baseline. Seventy-five (7%) had replacements of major joints. Risk factors at baseline for large joint replacement surgery were a low haemoglobin concentration [odds ratio scores (OR) 3.4, 95% confidence interval (CI) 2.1-5.8] and high scores for erythrocyte sedimentation rate (ESR) (OR 3.2, CI 1.8-5.3), disease activity (DAS) (OR 2.1, CI 1.2-3.5) and Larsen X-rays (OR 2.6, CI 1.4-4.8). For hand or foot joint surgery (4%), risk factors included female gender (OR 3.2, CI 1.3-7.6), joint score (OR 2.3, CI 1.2-4.3), erosions (OR 2.3, CI 1.1-4.8), DAS (OR 2.4, 1.3-4.5) and Health Assessment Questionnaire score (OR 1.9, CI 1.0-3.6). No significant associations were seen for tendon, soft tissue or other minor procedures (6%). The HLA-DRB1 RA shared epitope was associated with any type of orthopaedic surgery (OR 1.7, CI 1.1-2.7). CONCLUSIONS: Eleven per cent of RA patients treated with conventional drug therapy for 5 yr underwent large- or small-joint surgery, an outcome which could be compared against that for new disease-modifying drugs. Risk factors varied according to type of surgery, but included standard clinical and laboratory measures. In order to reduce the eventual need for surgery, a therapeutic target in the first year of RA is the suppression of disease activity, as measured by haemoglobin and ESR. These are useful details for clinicians, health professionals and patients.