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To estimate prevalence and incidence of cardiovascular (CV) risk factors of hypertension, diabetes mellitus, hyperlipidemia, and obesity in patients with rheumatoid arthritis (RA), psoriasis, or psoriatic arthritis (PsA).Patients with RA, psoriasis, or PsA were identified based on medical and pharmacy claims from the MarketScan claims databases from January 1, 2002 through December 31, 2014. Primary outcomes included age- and sex-standardized prevalence of CV risk factors during the 12 months preceding diagnosis date and incidence rates per 1,000 patient-years, with 95% confidence intervals (95% CIs) during followup.Prevalence for RA, psoriasis, and PsA cohorts for hypertension was 18.6% (95% CI 18.3-18.8), 16.6% (95% CI 16.3-17.0), and 19.9% (95% CI 19.4-20.4), respectively; for diabetes mellitus 6.2% (95% CI 6.1-6.4), 6.3% (95% CI 6.0-6.5), and 7.8% (95% CI 7.4-8.2); for hyperlipidemia 9.9% (95% CI 9.7-10.1), 10.4% (95% CI 10.2-10.7), and 11.6% (95% CI 11.2-12.0); and for obesity 4.4% (95% CI 4.2-4.6), 3.8% (95% CI 3.5-4.0), and 6.0% (95% CI 5.6-6.5). Incidence rates per 1,000 patient-years during followup for RA, psoriasis, and PsA cohorts, respectively, for hypertension were 74.0 (95% CI 72.5-75.5), 68.2 (95% CI 65.9-70.4), and 79.8 (95% CI 76.3-83.3); for diabetes mellitus 10.6 (95% CI 10.1-11.1), 13.0 (95% CI 12.1-13.8), and 14.7 (95% CI 13.5-16.0); for hyperlipidemia 40.3 (95% CI 39.4-41.3), 47.1 (95% CI 45.4-48.7), and 52.0 (95% CI 49.6-54.3); and for obesity 24.4 (95% CI 23.4-25.4), 26.4 (95% CI 25.0-27.8), and 32.9 (95% CI 30.6-35.2).Patients with RA, psoriasis, and PsA have high prevalence and incidence of CV risk factors, suggesting the need for risk factor monitoring of these patients.

Objectives Clinical joint activity is a strong predictor of joint damage in rheumatoid arthritis (RA), but progression of damage might increase despite clinical inactivity of the respective joint (silent progression). The aim of this study was to evaluate the prevalence of silent joint progression, but particularly on the patient level and to investigate the duration of clinical inactivity as a marker for non-progression on the joint level. Methods 279 patients with RA with any radiographic progression over an observational period of 3–5 years were included. We obtained radiographic and clinical data of 22 hand/finger joints over a period of at least 3 years. Prevalence of silent progression and associations of clinical joint activity and radiographic progression were evaluated. Results 120 (43.0%) of the patients showed radiographic progression in at least one of their joints without any signs of clinical activity in that respective joint. In only 7 (5.8%) patients, such silent joint progression would go undetected, as the remainder had other joints with clinical activity, either with (n=84; 70.0%) or without (n=29; 24.2%) accompanying radiographic progression. Also, the risk of silent progression decreases with duration of clinical activity. Conclusions Silent progression of a joint without accompanying apparent clinical activity in any other joint of a patient was very rare, and would therefore be most likely detected by the assessment of the patient. Thus, full clinical remission is an excellent marker of structural stability in patients with RA, and the maintenance of this state reduces the risk of progression even further.

Objective. To examine the correlation between disease activity of RA and the risk of falling.Methods. Seventy-eight patients were tested. Disease activity was measured with acute-phase reactants, autoantibodies, swollen and tender joint count (SJC28, TJC28), pain on a visual analogue scale (VAS pain), patient and evaluator global assessment of disease activity (PGA, EGA), HAQ disability index (HAQ-DI), 28-joint DAS (DAS-28) and the clinical and simple disease activity indexes (CDAI, SDAI). The risk of falling was evaluated by a fall assessment consisting of Tinetti test (TIT), timed get up and go test (TUG), chair-rising test (CRT), tandem walk and tandem stand test.Results. During the last 12 months, 26.9% of the participants reported a fall and 46.2% mentioned the fear of falling. The most evident link [Spearman's correlation (r(s))] with the results of the fall assessment was found in HAQ-DI (CRT: r(s) = 0.523, TUG: r(s) = 0.620, TIT: r(s) = -0.676), CDAI (CRT: r(s) = 0.460, TUG: r(s) = 0.504, TIT: r(s) = -0.472), VAS pain (CRT: r(s) = 0.441, TUG: r(s) = 0.616, TIT: r(s) = -0.548) PGA (CRT: r(s) = 0.473, TUG: r(s) = 0.577, TIT: r(s) = -0.520) and TJC (CRT: r(s) = 0.488, TUG: r(s) = 0.394, TIT: r(s) = -0.385). Patients with higher disease activity achieved poorer results in the fall assessment.Conclusion. The strongest correlation with falls was evident for patient-reported outcomes. Pain seems to be the common ground of these parameters. At the same time, disease activity influences pain. The results suggest an increased attention towards the risk of falling with patients of higher levels of disease activity or pain, and physio- or ergotherapeutical interventions as needed. Language: en

Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008–09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. Results. A total of 49 242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice. Conclusions. Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.

BackgroundPhysical disability is a main outcome in rheumatoid arthritis (RA) which tends to increase with comorbidities. However, the extent to which comorbidities contribute to the multifactorial process of disability has not been investigated.ObjectiveTo quantify the contribution of comorbidity to physical disability in patients with RA.MethodsIn a prospective cohort study, age-adjusted Charlson comorbidity index (CCIA), serial measurements of disease activity and functional disability (evaluated by the Health Assessment Questionnaire Disability Index, HAQ) of 380 patients with established RA seen at an outpatient clinic over 1 year (June 2007 to July 2008) were ascertained. The association between comorbidity and physical disability was assessed using analysis of variance (ANOVA) and adjusted general linear regression models.ResultsFour patient groups with increasing levels of comorbidity (CCIA 0, 1–2, 3–4 and 5–9; potential range 0–38) were defined. Mean HAQ scores were significantly different across these groups (0.67, 0.80, 1.24, 1.40, respectively; pA on disability were similar within different strata of disease activity: namely, remission (0.26, 0.31, 0.48 and 0.88, pConclusionPhysical disability becomes worse with increasing levels of comorbidity, irrespective of disease activity.

Objective To examine in detail the outcomes of biologic DMARD (bDMARD) discontinuation while in remission occurring in daily clinical practice settings. We examined a multicentre longitudinal registry of RA patients. Methods We utilized data from the NinJa multicenter registry in Japan. Patients who used bDMARDs and had one or more successive visits in remission (defined by the clinical disease activity index (CDAI) ≤2.8) before discontinuation were included. The outcome of failing bDMARD-free disease control was defined as a composite of the following: re-use of bDMARDs, intensification of non-biologic DMARDs or of oral glucocorticoids, or loss of CDAI remission. Results Among 1037 patients who initially achieved remission on bDMARDs, 46 patients discontinued bDMARDs while remaining in remission. Of these 46 subjects, 41 (89.1%) were female, the median disease duration was 6.0 years and 31 (70.5%) had reported radiographical erosions. At the baseline, 27 (58.7%) used MTX and 19 (41.3%) used oral glucocorticoids. The bDMARD-free remission failure rate was estimated to be 67.4% at 1 year and 78.3% at 2 years. Loss of remission and reuse of bDMARDs were the more common reasons for failure. Lower CDAI within the remission range was associated with fewer failures. Conclusion We found a high rate of failing bDMARD-free CDAI remission, indicating difficulty of maintaining disease control, even in patients who were in remission. Modification of non-biologic treatment was observed in some of the patients who remained in remission. Considering the cost of bDMARDs, such strategies for maintaining disease control after bDMARD discontinuation may be an important option.

Objective.We conducted a longitudinal observational study of biological disease-modifying antirheumatic drugs (bDMARD) to describe the proportions of patients with rheumatoid arthritis in remission who discontinued these agents, and to assess the potential predictors of the decision to discontinue.Methods.We used data from the US COnsortium of Rheumatology Researchers Of North America (CORRONA) and the Japanese National Database of Rheumatic Diseases by iR-net in Japan (NinJa) registries, and ran parallel analyses. Patients treated with bDMARD who experienced remission (defined by the Clinical Disease Activity Index ≤ 2.8) were included. The outcome of interest was the occurrence of bDMARD discontinuation while in remission. The predictors of discontinuation were assessed in the Cox regression models. Frailty models were also used to examine the effects of individual physicians in the discontinuation decision.Results.The numbers of eligible patients who were initially in remission were 6263 in the CORRONA and 744 in the NinJa. Among these patients, 10.0% of patients in CORRONA and 11.8% of patients in NinJa discontinued bDMARD while in remission over 5 years, whereas many of the remaining patients lost remission before discontinuing bDMARD. Shorter disease duration was associated with higher rates of discontinuation in both cohorts. In CORRONA, methotrexate use and lower disease activity were also associated with discontinuation. In frailty models, physician random effects were significant in both cohorts.Conclusion.Among patients who initially experienced remission while receiving bDMARD, around 10% remained in remission and then discontinued bDMARD in both registries. Several factors were associated with more frequent discontinuation while in remission. Physician preference likely is also an important correlate of bDMARD discontinuation, indicating the need for standardization of practice.

Objective.Current recommendations advocate treatment with disease-modifying antirheumatic drugs (DMARD) in all patients with active rheumatoid arthritis (RA). We investigated the frequency of and reasons for inconsistent DMARD use among patients in a clinical rheumatology cohort.Methods.Patients in the Brigham Rheumatoid Arthritis Sequential Study were studied for DMARD use (any or none) at each semiannual study timepoint during the first 2 study years. Inconsistent use was defined as DMARD use at ≤ 40% of study timepoints. Characteristics were compared between inconsistent and consistent users (> 40%), and factors associated with inconsistent DMARD use were determined through multivariate logistic regression. A medical record review was performed to determine the reasons for inconsistent use.Results.Of 848 patients with ≥ 4 out of 5 visits recorded, 55 (6.5%) were inconsistent DMARD users. Higher age, longer disease duration, and rheumatoid factor negativity were statistically significant correlates of inconsistent use in the multivariate analyses. The primary reasons for inconsistent use identified through chart review, allowing for up to 2 co-primary reasons, were inactive disease (n = 28, 50.9%), intolerance to DMARD (n = 18, 32.7%), patient preference (n = 7, 12.7%), comorbidity (n = 6, 10.9%), DMARD not being effective (n = 3, 5.5%), and pregnancy (n = 3, 5.5%). During subsequent followup, 14/45 (31.1%) inconsistent users with sufficient data became consistent users of DMARD.Conclusion.A small proportion of patients with RA in a clinical rheumatology cohort were inconsistent DMARD users during the first 2 years of followup. While various patient factors correlate with inconsistent use, many patients re-start DMARD and become consistent users over time.

Since the introduction of tumor necrosis factor (TNF)-α inhibitors, the treatment of rheumatoid arthritis (RA) has been revolutionized. The approach of targeting TNF-α has considerably improved the success in the treatment of RA. Over the last 3 decades five different TNF-α inhibitors have been administered: infliximab, etanercept, adalimumab, golimumab, and certolizumab-pegol. All of them show excellent efficacy with similar rates of clinical response and prevention of radiographic disease progression. With improved therapies, treatment strategies have also changed, with the aims now being to achieve and maintain remission. Most recently, the discussion expands to the issue of treatment reduction in patients who have achieved sustained remission; here, the discontinuation of TNF-α inhibitor therapy has become an area of interest, given obvious economic and risk-benefit evaluations. However, only little is known if “biologic free” remission is possible in patients with sustained remission following intensive TNF-α inhibitor therapy.

Background: Patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions.\ud \ud Objectives: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide.\ud \ud Methods Study design: international, cross-sectional. Patients: consecutive RA patients. Data collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders).\ud \ud Results: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)–erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%.\ud \ud Conclusions: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.

Rheumatoid arthritis (RA) is among the most disabling form of chronic inflammatory joint disease. Not all forms of arthritis develop into RA; on the contrary, it may be very challenging to differentiate RA from cases of arthritis that are self-limiting or caused by another disease. Evaluation of early arthritis includes some basic steps, such as excluding trauma, crystal, or infectious-related disease, as well as considering additional features that may guide towards a specific diagnosis. If no specific diagnosis can then be made, the presentation can be labelled as undifferentiated arthritis. Typical differential diagnoses of RA include viral polyarthritis, seronegative spondylarthropathies, polymyalgia rheumatic, and other systemic rheumatic diseases. In 2010, new classification criteria were published that led to a change in the approach to RA. Compared to the previous criteria, the American College of Rheumatology (ACR) 1987 criteria, a scoring system was devised, appreciating the type and number of affected joints (up to 5 points), as well as serology (up to 3 points), elevated acute-phase reactants (1 point), and a symptom persistence of 6 weeks or longer (1 point). If 6 or more points are reached, then classifiable RA is present. Importantly, classification status, which is used for study purposes, is not always identical to the diagnostic status, which often leads to clinical treatment.

Rheumatoid arthritis (RA) is among the most disabling form of chronic inflammatory joint disease. Not all forms of arthritis develop into RA; on the contrary, it may be very challenging to differentiate RA from cases of arthritis that are self-limiting or caused by another disease. Evaluation of early arthritis includes some basic steps, such as excluding trauma, crystal, or infectious-related disease, as well as considering additional features that may guide towards a specific diagnosis. If no specific diagnosis can then be made, the presentation can be labelled as undifferentiated arthritis. Typical differential diagnoses of RA include viral polyarthritis, seronegative spondylarthropathies, polymyalgia rheumatic, and other systemic rheumatic diseases. In 2010, new classification criteria were published that led to a change in the approach to RA. Compared to the previous criteria, the American College of Rheumatology (ACR) 1987 criteria, a scoring system was devised, appreciating the type and number of affected joints (up to 5 points), as well as serology (up to 3 points), elevated acute-phase reactants (1 point), and a symptom persistence of 6 weeks or longer (1 point). If 6 or more points are reached, then classifiable RA is present. Importantly, classification status, which is used for study purposes, is not always identical to the diagnostic status, which often leads to clinical treatment.

Many studies have been conducted concerning discontinuation of biologic disease-modifying anti-rheumatic drugs (DMARD), but mainly in trial settings which result in limited generalisability. Registry studies can complement the current literature of biologic DMARD discontinuation by providing more generalisable information. However, it may be necessary to combine registries to increase power and provide more diverse patient populations. This increased power could provide us information about risk and benefits of discontinuing biologic DMARD in typical clinical practice. However, use of multiple registries is not without challenges. In this review, we discuss the challenges to combining data across multiple registries, focusing on biologic discontinuation as an example. Challenges include: 1) generalizability of each registry; 2) new versus prevalent users designs; 3) outcome definitions; 4) different health care systems; 5) different follow up intervals; and 6) data harmonisation. The first three apply to each registry, and the last three apply to combining multiple registries. This review describes these challenges, corresponding solutions, and potential future opportunities.

Background It was previosly shown that metacarpal cartilage thickness (MCT) as assessed by ultrasound (US) correlates with both radiographic joint space width (JSW) and joint space narrowing (JSN) in the metacarpophalangeal joints (MCP) of patients with rheumatoid arthritis (RA). Objectives To correlate change in MCT with change in radiographic JSW and JSN in a longitudinal study of patients with RA. Methods We performed US examination of 19 consecutive outpatients with RA fulfilling the 2010 ACR/EULAR classification criteria with recent hand X-rays. Metacarpal cartilage of MCP 2–5 was assessed bilaterally by US at baseline and after 3 years in mm with an integrated caliper on static images (Figure 1A). JSN was evaluated on X-rays taken Results Over the study period of 3 years a mean change of MCT of 0.00±0.01mm, was paralleled by a mean change of JSW of -0.08±0.20mm and a change of 0.12±0.37 in the JSN component of the vdHS. Change in MCT correlated with change in JSW (r: 0.37; p: Conclusions Change in sonographic cartilage thickness correlates with radiographic measures of joint space narrowing in the MCP joints of RA patients over time. Thus, ultrasound may be a valid tool for the longitudinal assessment of metacarpal cartilage in RA patients, but also the radiographic assessments appear to reflect “true” cartilage dimensions. Disclosure of Interest None declared

Background Hepcidin is an important link between inflammation and anemia in patients with rheumatoid arthritis (RA); hemoglobin itself is considered a negative acute phase measure in chronic inflammatory conditions like RA. However, the longitudinal association of hepcidin and hemoglobin with RA disease activity and acute phase remains to be explored. Objectives We aimed to explore these associations in patients with RA. Methods We consecutively included RA outpatients in a routine academic setting. Each patient was evaluated at baseline and 12 weeks thereafter using the clinical disease activity index (CDAI) and extensive peripheral blood tests, including serology, acute phase response (erythrocyte sedimentation rate, ESR; C reactive protein, CRP; and fibrinogen) and measures of iron metabolism (ferritin; transferrin; transferrin saturation, TS; hepcidin; and peripheral erythroid burst forming units, BFU-E). We analyzed baseline and week 12 values cross-sectionally in all patients; and change scores from baseline to week 12 in a subset of active patients with CDAI≥10 and a new DMARD initiation at baseline. We performed principal component analysis (PCA) to identify themes for all included variables. The strength of association of hepcidin and hemoglobin with the identified themes from the PCA was then analyzed. Results Eighty-eight patients (68 females, 77%) were included (mean±SD age: 58±12 years; disease duration: 9.3±9.6 years). PCA identified four themes for all included parameters: clinical activity, acute phase, iron metabolism and hematopoiesis. At baseline and week 12 (steady state), both hepcidin and hemoglobin levels were ascribable primarily to the theme “iron metabolism”. Hemoglobin was also ascribable to “clinical activity” – to a similar extent as other acute phase parameters; but even more to the theme “acute phase”. Conversely, 12-week changes in hepcidin levels were ascribable to “changes in acute phase”, while changes in hemoglobin levels were ascribable to “changes in clinical activity” (Figure). In multivariable analysis CDAI changes were negatively, and BFU-E changes were positively, associated with hemoglobin changes (R 2 =0.615, p Figure: Loadings of hepcidin (solid lines) and hemoglobin (dotted lines) to the themes identified by principal component analysis, for baseline values (left), and for changes between baseline and week 12 (right) Conclusions In patients with RA, changes in hepcidin levels reflect changes in acute phase response, but not changes in clinical disease activity; changes in hemoglobin levels occur in conjunction with changes in clinical disease activity, but not with changes of the acute phase response. The association of clinical disease activity with hemoglobin seems to be stronger than its association with other acute phase parameters. References Song SN et al. Arthritis Res Ther. 2013;15:R141. Disclosure of Interest None declared

Background There is considerable variation in the type of information used in rheumatoid arthritis (RA) observational studies. This, in turn, makes collaborative RA observational research challenging. As part of a larger initiative (EULAR Task Force) a step-wise approach was designed in order to achieve a consensus on a standardized minimum core dataset (MCD) with items (i.e. “what to collect”) and instruments (i.e. “how to collect”). Objectives To undertake a literature review designed to construct a comprehensive list of items and instruments currently collected across observational RA studies in Europe. This will ultimately inform the development of a MCD for collaborative RA research. Methods A hierarchical literature review of published articles that were I) observational cohorts or registers II) including RA patients and III) were initiated in Europe, was performed. Results were compared and cross-checked with EULAR recommendations for data reporting in RA clinical trials and trial extension studies for management of RA, The EULAR outcome measures library (OML) and the results of an initial survey undertaken by our group1. The latter was a web-survey involving a smaller sample of RA registers and clinical cohorts. The current literature review expanded to involve all existing RA registers and cohorts in published literature. From the literature, information of what is collected (item) and how (instrument) was extracted and the frequency of data collection was calculated. Results Published articles from 67 different European RA registers and cohorts were included. The number of patients recruited in each register ranged from 130 to more than 50,000. A total of 40 different items were identified comprising >100 different instruments Most studies included a measure of disease duration, disease activity, current DMARD use or physical function although the choice of instrument within each item varied widely in many cases (table 1). For example, 8 different composite scores of disease activity are being captured. Relative agreement on specific items did not always, however, entail agreement in terms of instruments. Conclusions Information captured in registers is heterogeneous. The frequency of collection of items and instruments informed voting in the first face-to-face meeting, alongside the expert panel survey. References Radner H. el al. Consistency and utility of data items across European rheumatoid arthritis clinical cohorts and registers. Arthritis Care Res 2015 Disclosure of Interest None declared

Background Studies have suggested that the chronic inflammatory nature of rheumatic conditions (rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) as well as psoriasis (PsO) may predispose patients to cardiovascular (CV) disease and metabolic disorders. However, the individual impact of RA, PsA, and PsO on traditional CV risk factors is not well understood. Objectives We estimated the incidence and prevalence of traditional CV risk factors - hypertension, diabetes mellitus (DM), hyperlipidemia, and obesity - among three separate cohorts of patients with RA, PsA, or PsO. Methods Patients with RA, PsA, and PsO between January 1, 2002 and June 30, 2014 were identified (and included in three separate cohorts) in the Truven Health MarketScan Commercial and Medicare Supplemental databases. Index date was defined as the date of RA, PsA or PsO diagnosis. Patients were required to be continuously enrolled for 12 months prior to the index date. Follow-up time for the identification of the CV risk factors began on the day after index date and continued until disenrollment from MarketScan, or the end of the study. The primary outcome was the first occurrence of the CV risk factors during the follow-up period. Incidence rates (IR) per 1,000 patient-years (PY) with 95% confidence intervals (CI) were calculated. The prevalence (number of cases/total population) of CV risk factors prior to the index date was also calculated. Results We identified 266,167 patients with RA, 35,050 with PsA, and 301,593 with PsO. Mean age at index date was similar for both PsO and PsA patients (51 yrs), but RA patients were older (58 yrs). Mean follow-up time ranged from 2.3 years to 2.5 years. Prevalence of the CV risk factors ranged as follows: hypertension 24.7% in PsO to 34.6% in RA; DM 8.2% in PsO to 10.4% in RA; Hyperlipidemia 16.5% in PsO to 18.2% in RA; and Obesity 5.1% in PsO to 6.7% in PsA. The pattern of CV risk factors development after RA, PsA, and PsO diagnosis was similar as prior to diagnosis. The RA cohort demonstrated the highest incidence of hypertension and hyperlipidemia whereas PsA cohort demonstrated the highest incidence of DM and obesity. All risk factors were lowest in the PsO cohort (Table 1). Conclusions The incidence rates of hypertension, hyperlipidemia, DM, and obesity are higher among patients with RA and PsA compared to patients with PsO. Differences in levels of systemic inflammation may underpin differences in rates of risk factors. Different treatment strategies may be useful in preventing these comorbidities. The results highlight the importance of close monitoring and managing CV risk factors in patients with RA, PsA and PsO. Disclosure of Interest D. Solomon Consultant for: Amgen Inc and received a research contract to assist with these analyses, T. Lesperance Employee of: Amgen Inc, H. Radner Consultant for: Amgen Inc and received a research contract to assist with these analyses, N. Accortt Employee of: Amgen Inc

Background Collaborative research is compromised by heterogeneity of data collection in observational rheumatoid arthritis (RA) databases. Therefore a EULAR taskforce has been convened to develop a minimum core dataset (MCD) to 1) harmonize future data collection 2) act as a common data model existing databases can be mapped to 3) serve as a template for standardized data collection for RA research in clinical practice. Objectives To identify data items (i.e. “what to collect”) and instruments (i.e. “how to collect”) for inclusion in a MCD using an online survey. Methods First we performed a hierarchical literature review to identify data items and instruments of existing RA cohorts/registers. Extracted data presented in a separate abstract were used to develop an online survey to gather information from an expert panel involving Presidents of National Societies and selected representatives from each European country, patients, rheumatologists, other health professionals, and researchers. Experts were asked to rate importance of 48 different items and their instruments for possible inclusion in a MCD on a scale from 1 (not important) to 9 (very important). For analyses ratings of 1–3 (NO inclusion) and of 7–9 (INCLUSION) were combined and percentages of responses calculated. Results 90 experts from 28 different European countries (patients 18%, health professionals 18%, physicians 55%, researchers 10%) participated in the survey. 27/48 items were regarded to be important for inclusion in a MCD by >80% of responders. Highest level of agreement to INCLUDE an item was found for: diagnosis of RA, composite scores, tender and swollen joint count (100%; table). Discrepancies of rating were observed for instruments: 24/126 instruments were rated as important for inclusion by >80% of responders. Conclusions Based on expert ratings the majority of items were considered appropriate for inclusion into a MCD, leading to an extensive template. For most instruments no consensus was achieved. Results of the survey were moved forward onto the next phase of the project. Disclosure of Interest H. Radner: None declared, E. Nikiphorou: None declared, K. Chatzidionysiou: None declared, L. Gossec: None declared, K. Hyrich: None declared, C. Filip: None declared, Y. van Eijk-Hustings: None declared, P. Williamson: None declared, W. Dixon Grant/research support from: EULAR health professional research grant, J. Askling Grant/research support from: EULAR health professional research grant

Objective. To assess the efficacy and safety of combination pain therapy for people with inflammatory arthritis (IA). Methods. Systematic review of randomized controlled trials using Cochrane Collaboration methodology. Combination therapy was defined as at least 2 drugs from the following classes: analgesics, nonsteroidal antiinflammatory drugs (NSAID), opioids, opioid-like drugs, and neuromodulators (antidepressants, anticonvulsants, and muscle relaxants). The main efficacy and safety outcomes were pain and withdrawals due to adverse events, respectively. Results. Twenty-three trials (total of 912 patients) met inclusion criteria [22 in rheumatoid arthritis (RA) and 1 in a mixed population of RA and osteoarthritis]. All except 1 were published before 1990. All trials were at high risk of bias, and heterogeneity precluded metaanalysis. Statistically significant differences between treatment groups were reported in only 5/23 (22%) trials: in 3 trials combination therapy was better (2 trials with NSAID + analgesic versus NSAID only and I trial with 2 NSAID versus 1 NSAID), in 1 trial combination therapy was worse (opioid + neuromodulator versus opioid only), and in the fifth trial (NSAID + analgesic versus NSAID alone) reported results were mixed depending on the dosage used in the monotherapy arm. In general, there were no differences in safety and withdrawals due to inadequate analgesia between combination and monotherapy. Conclusion. Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for pain management in IA. Well-designed trials are needed to address this question. (J Rheumatol Suppl 2012; Sept;90:47-55; doi:10.3899/jrheum.120342)

Objective Patients and physicians often differ in their perceptions of rheumatoid arthritis (RA) disease activity, as quantified by the patient's global assessment (PGA) and by the evaluator's global assessment (EGA). The purpose of this study was to explore the extent and reasons for this discordance. Methods We identified variance components for the PGA and EGA in RA patients who were starting therapy with methotrexate in an academic outpatient setting. We analyzed predictors of the observed discrepancy in these measures (calculated as the PGA minus the EGA) and in their changes (calculated as the PGAchange minus the EGAchange). Results We identified 646 RA patients, and among them, 77.4% of the variability in the PGA and 66.7% of the variability in the EGA were explainable. The main determinants for the PGA were pain (75.6%), function (1.3%, by Health Assessment Questionnaire), and number of swollen joints (0.5%); those for the EGA were the number of swollen joints (60.9%), pain (4.5%), function (0.6%), C-reactive protein (0.4%), and the number of tender joints (0.3%). Increased pain led to a discrepancy toward worse patient perception, while increased numbers of swollen joints led to a discrepancy toward worse evaluator perception, both explaining 65% of the discordance between the PGA and the EGA. Likewise, changes in pain scores and numbers of swollen joints proved to be the main determinants for discrepant perceptions of changes in RA disease activity, explaining 34.6% and 12.5% of the discordance, respectively. Conclusion The most significant determinants for the cross-sectional and longitudinal discrepancy between the PGA and the EGA are pain and joint swelling, respectively. Understanding the reasons for a discordant view of disease activity will help to facilitate the sharing of decision-making in the management of RA.

Objective Anti–citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and are present years before the onset of symptoms. The avidity of autoantibodies can have a strong impact on their effector potency. This study was undertaken to analyze the avidity of ACPAs in serum samples obtained from ACPA-positive healthy individuals (predisease), patients with early disease, and patients with established RA as well as the avidity maturation over time in samples from healthy subjects who later developed RA. Methods We measured ACPA avidity in serum samples from ACPA-positive healthy individuals, symptomatic individuals, and patients with established RA in 5 collections from The Netherlands, Canada, and Austria. We determined the dynamics of avidity maturation of ACPAs from the predisease stage to established disease in 1 case from the native North American population and in 10 cases from a Dutch blood donor cohort. Results The overall ACPA response was characterized by low-avidity antibodies. Higher-avidity ACPAs were observed in symptomatic patients only, while low-avidity ACPAs were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, ACPA avidity increased over time until disease onset. No further avidity maturation was observed after disease onset. Conclusion Our findings indicate that avidity maturation of the ACPA response takes place prior to disease onset.

Background Even with optimal disease-modifying treatment and good control of disease activity, persistent pain due to structural damage is common in people with inflammatory arthritis and therefore additional treatment for pain might be required. Because comorbidity is highly prevalent in people with inflammatory arthritis, it is important to consider comorbidities such as gastrointestinal or liver diseases in deciding upon optimal pharmacologic pain therapy. Objectives To assess the efficacy and safety of pharmacological pain treatment in patients with inflammatory arthritis who have gastrointestinal or liver comorbidities, or both. Search methods We searched Cochrane CENTRAL, MEDLINE and EMBASE for studies, to June 2010. We also searched the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) conference abstracts (2007 to 2010) and performed a handsearch of reference lists of articles. Selection criteria All randomised or quasi-randomised controlled trials (RCTs or CCTs) were considered for inclusion, for the assessment of efficacy. For safety, we also considered single arm trials, controlled before-after studies, interrupted time series, cohort and case-control studies, and case series of 10 or more consecutive cases. Pain therapy comprised paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs (tramadol) and neuromodulators (antidepressants, anticonvulsants and muscle relaxants). The study population comprised adults (≥ 18 years) with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis who had gastrointestinal or hepatic, or both, comorbid conditions. Outcomes of interest were pain, adverse effects, function and quality of life. Studies that included a mixed population of inflammatory arthritis and other conditions were included only if results for inflammatory arthritis were reported separately. Data collection and analysis Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data. Main results From 2869 identified articles only one single arm open trial fulfilled our inclusion criteria. This trial assessed the safety and efficacy of naproxen (dosage not specified) in 58 patients with active rheumatoid arthritis and gastrointestinal comorbidities for up to 52 weeks. Thirteen participants (22%) remained on gold therapy, four participants (10%) remained on hydroxychloroquine, 27 (47%) remained on corticosteroids, 12 (21%) remained on salicylates and all participants continued on antacids and a bland diet. The presence of faecal occult blood was reported in 1/58 participants tested between weeks 1 to 26 and 2/32 participants tested between weeks 27 to 52. Over the course of the study, seven participants (12.1%) withdrew due to adverse events but, of these, only two participants withdrew due to gastrointestinal side effects (abdominal pain n = 1, nausea n = 1) and no serious adverse events were reported. It was noteable that out of 14 studies excluded due to inclusion of a mixed population (osteoarthritis or other rheumatic conditions) or an intervention that was already withdrawn, five trials reported a higher risk of developing gastrointestinal events in patients with prior gastrointestinal events when treated with NSAIDs. Authors' conclusions On the basis of the current review, there is scant evidence to guide clinicians about how gastrointestinal or liver comorbidities should influence the choice of pain treatment in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis. Based upon additional studies that included a mixed population of participants with a range of rheumatic conditions, NSAIDs should be used cautiously in patients with inflammatory arthritis and a history of gastrointestinaI comorbidity as there is consistent evidence that they may be at increased risk.

Background Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. Objectives To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and other spondyloarthritis (SpA)). We planned to assess differences in effects between patients on background disease-modifying antirheumatic drug (DMARD) therapy and patients on no background therapy in subgroup analyses. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; and EMBASE. We did not impose any date or language restrictions in the search. We also handsearched conference proceedings of the American College of Rheumatology and the European League against Rheumatism (2008-10). Selection criteria Randomised and controlled clinical trials (RCTs and CCTs) assessing combination therapy (at least two drugs from the following classes: analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs and neuromodulators (antidepressants, anticonvulsants and muscle relaxants)) compared with monotherapy, for adults with IA (RA, AS, PsA and other SpA). We speficically excluded studies that did not report pain or studies without a standardised pain scale as an outcome measure. Data collection and analysis Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data. Main results Twenty-three trials (total of 912 patients) met the inclusion criteria (22 in RA; one in a mixed population of RA and osteoarthritis); all except one were published before 1990. Most study populations were not taking DMARDs (e.g. methotrexate, sulphasalazine, hydroxychloroquine and leflunomide) and all studies were performed prior to the introduction of biologic therapies (e.g. etanercept, infliximab and adalimumab). All trials were at high risk of bias, heterogeneity precluded meta-analysis, and we were only able to report a general description of results. The majority (18 studies, 78%) found no differences between the combination and monotherapy treatments they studied, while five (22%) reported conflicting results, favouring either the combination or monotherapy arms. From the 12 trials on NSAID + analgesic vs NSAID, nine reported no significant difference between the interventions, while three did: in two, the combination therapy achieved better pain control; and the third trial compared combination therapy with two different dosages of monotherapy (NSAID alone) and reported that a high dose phenylbutazone was superior to combination therapy (paracetamol + aspirin), which was superior to low dose phenylbutazone. From the five studies on the combination of two NSAIDS vs one NSAID, four reported no significant differences between interventions, and one reported significantly better pain control with combination therapy. The single trial comparing a combination of opioid + neuromodulator vs opioid reported better pain control with monotherapy. The remaining trials (NSAID + neuromodulator vs NSAID (3 trials); opioid + NSAID vs NSAID (1 trial); and opioid + analgesic vs analgesic (1 trial)) found no significant difference between combination therapy and monotherapy. Information regarding withdrawals due to inadequate analgesia and safety was incompletely reported, but in general there were no differences between combination therapy and monotherapy. No data were available that addressed the value of combination pain therapy or monotherapy for people with IA who have optimal disease suppression. There were no studies that included patients with AS, PsA or SpA. Authors' conclusions Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for people with IA. Importantly, there are no studies addressing the value of combination therapy for patients with IA who have persistent pain despite optimal disease suppression. Well designed trials are needed to address this question.

Objective. Comorbidities have been reported to influence physical function, but it is not clear which activities are predominantly impaired, or which other domains of health status are affected in addition to physical function. In this study, we investigated the impact of comorbidities on individual activities of daily living, and other aspects of quality of live in patients with RA. Methods. In 380 patients with established RA, we quantified comorbidity levels according to the age-adjusted Charlson Comorbidity Index (CCIA) and functional disability by serial measures of the HAQ over 1 year. In a subset of 185 patients, we assessed quality of life using Short Form-36 (SF-36). To analyse the relationship between comorbidities, different activities of daily living and health status, we divided patients into four subgroups of CCIA and performed analysis of variance (ANOVA) and multivariable general linear regression models adjusted for gender, disease duration and disease activity. Results. ANOVA showed significant (P < 0.03) increase of disability within each domain of HAQ with increasing level of comorbidity. Similar results were observed using the physical component score (P = 0.003) of the SF-36 and its domains, whereas mental component score (P = 0.31) and its domains were unaffected by comorbidities. In a sub-analysis stratifying patients into different levels of disease activity, we found increase in almost all domains of HAQ within respective groups of CCIA. Conclusions. Activities of daily living represented by HAQ are equally affected by comorbidities. More generally, health status was only affected with respect to its physical but not its mental domains.

Background Lower levels of dehydroepiandrosterone sulphate (DHEAS) were found in chronic inflammatory diseases such as rheumatoid arthritis (RA), however, mechanisms for this decrease remains unclear. Recently, several genes has been found to be associated with lower DHEAS levels [1]. Objectives The aim of our study was to analyze frequency of selected single nucleotide polymorphisms (SNPs) known to be associated with low DHEAS in RA patients and their impact on DHEAS levels during disease. Methods 1034 participants (438 RA, 596 controls) were analyzed for SNPs in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306) and ARPC1A (rs740160) by real-time PCR genotyping assay. Serum DHEAS concentration was measured in 156 RA patients and 102 healthy controls by ELISA. Results RA patients had significantly lower DHEAS than controls (age-adjusted), in female (p Conclusions Complex interactions exist between DHEAS-associated genotypes and adrenal androgen hypofunction in RA suggesting a significant contribution to adrenal androgen hypofunction in RA. References Zhai G et al. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. PLoS Genet. 2011; 7(4):e1002025. Acknowledgements Study was supported by VEGA 2/0018/12 Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5779

Background Current recommendations advocate treatment with disease-modifying anti-rheumatic drugs (DMARDs) in all patients with active rheumatoid arthritis (RA). However, results from contemporary RA cohorts show that even in specialized rheumatology clinics, a proportion of patients are not treated with DMARDs. Objectives We investigated the frequency of and reasons for inconsistent DMARD use among patients in a clinical rheumatology cohort. Methods Patients in the Brigham Rheumatoid Arthritis Sequential Study were studied for DMARD use (any or none) at each semi-annual study time point during the first two study years. Inconsistent use was defined as DMARD use at ≤40% of study time points. Characteristics were compared between inconsistent and consistent users (>40%), and factors associated with inconsistent DMARD use were determined through multivariate logistic regression. A medical record review was performed to determine the reasons for inconsistent use. Results Of 848 patients with sufficient follow-up data, 55 (6.5%) were inconsistent DMARD users. Higher age, longer disease duration and rheumatoid factor negativity were statistically significant correlates of inconsistent use in the multivariate analyses (table). The primary reasons for inconsistent use identified through chart review, allowing for up to 2 co-primary reasons, were inactive disease (n=28, 50.9%), intolerance to DMARDs (n=18, 32.7%), patient preference (n=7, 12.7%), comorbidity (n=6, 10.9%), DMARDs not being effective (n=3, 5.5%), and pregnancy (n=3, 5.5%). During subsequent follow-up, 14/45 (31.1%) of inconsistent users with sufficient data became consistent users of DMARDs. Conclusions A small proportion of RA patients in a clinical rheumatology cohort were inconsistent DMARD users during the first two years of follow up. Several patient factors correlate with inconsistent use, and many patients re-start DMARDs and become consistent users over time. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2217

Background Multimorbidity is an important patient-centered concept that needs to be considered when deciding on diagnostic or therapeutic strategies for typical rheumatoid arthritis (RA) patients. In chronic diseases like RA, health related quality of life (HRQol) is the main outcome. An index reflecting multimorbidity (MMI) that is based on HRQoL would be novel, as existing indices are commonly comorbidity indices based on more unidimensional outcomes, such as mortality, costs or function. A MMI would be helpful to better address the disease-related aspect of patients9 overall well-being. Objectives To develop a multimorbidity index (MMI) based on HRQoL. Methods The index was developed in an RA cohort, the Brigham and Women9s Hospital Rheumatoid Arthritis Sequential Study (BRASS). 40 specific morbidities recommended as core by a systematic literature review were identified using ICD-9 codes; the primary outcome was EQ-5D. Two types of MMI were calculated, one by simply enumerating concomitant morbidities (MMIc), and another one by weighing mobid conditions based on their association with HRQoL (using EQ5D) in a multiple linear regression analysis (weights derived from β-coefficients of the regression model) (MMIw). Performance of both MMI was compared to the Charlson comorbidity index (CCI). Results In total 544 out of 876 patients were multimorbid, defined as ≥2 morbid conditions. MMIc ranged from 1-16 (median 2; 25th/75th percentile 1/3); MMIw ranged from 0 – 38 (mean±SD 3.8±6.1). Both indices were similarly associated with EQ-5D, and significantly more strongly than the established CCI (Correlation coefficient r (95CI)%: MMIc -0.21 (-0.15 to -0.28); MMIw -0.32 (-0.26 to -0.38), CCI -0.10 (-0.03 to -0.15); p 2 obtained by linear regression models using EQ-5D as dependent variable and the two Indices as independent variable, adjusted for age and gender was highest for MMI (R 2 : MMIc 0.05, MMIw 0.11, CCI 0.01). When accounting for RA disease activity (using Clinical disease activity index CDAI) R 2 increased (R 2 MMIc 0.18; MMIw 0.22; CCI 0.17), still showing highest values of MMI compared to CCI. The predictive validity of the MMI was robust as demonstrated by the agreement of predicted values of EQ5D after one year with observed values of EQ5D after one year (Spearman r: MMIc 0.34, MMIw 0.37; both p Conclusions In our cohort, the novel MMI showed a better relationship with HRQol than the well known CCI. A simple enuneration of morbid conditions is similarly effective as a HRQoL weighted index, and could therefore be useful to control for the effect of multimorbidity on patient9s overall well being. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3405

Background Heterogeneity in terms of data collection is thought to limit comparability and pooling of data in Rheumatoid Arthritis (RA) clinical cohorts and registers across Europe. Defining such standards should be informed by which data items are currently collected, how they are defined and collected, and their perceived utility. Objectives To identify overlaps, discrepancies, and perceived usefulness of the currently collected data in existing RA clinical cohorts and registries. Methods A survey was developed and sent to 29 European RA registers and clinical cohorts. The survey requested information on: IF specific data items are collected, HOW and with what Frequency they are collected, how often data are MISSING, and if these items are regarded as USEFUL for research purposes. Results 25 cohorts/registers with different inclusion criteria and definition of RA completed the survey, totaling 189,043 patients (range: 130 to 55,000). 6/25 cohorts (24%) were established before year 2000, 60% were multi-center collections. The figure displays frequency of collected data items. There were differences in HOW items were defined (Composite Scores (CoSc): 80%DAScrp/DAS4items, 40%SDAI/CDAI, 8%Ritchie Index; Joint Counts (JC): 71%28JC, 5%66JC; pain 25%general pain, 35%pain related to arthritis) and HOW they were collected (JC: 54% total JC, 46% individual joints; pain: 85% VAS, 20% numeric rating scale; Comorbidities: 57%patient self reported, 29%standardized questionnaire; 10%free text; 33%records). Items with higher proportions of missing information were EQ-5D, and fatigue. DMARD history and serology were collected mainly at baseline only, whereas items of disease activity and severity such as JC, CoSc, pain, and HAQ were collected at almost every follow up visit. CoSc (92%), disease duration (92%), biologic DMARDs (91%) and HAQ (91%) were most frequently used for research. Among all items collected, the responders ranked disease activity, treatment, and JC as the most essential, compared to extra-articular manifestations, smoking and imaging which had the lowest perceived utility. At the same time, smoking, imaging, co-morbidities and adverse event data were the top-ranked data items responders felt was missing from their data collection. Conclusions Even though common core items such as disease activity, treatment and comorbidities have been identified, the mode of data collection is heterogeneous. To facilitate future data sharing and combined analytical approaches, data collection across Europe needs to be better harmonized. Disclosure of Interest : H. Radner Grant/research support: IMI BT-Cure Project, K. Hyrich: None declared, W. Dixon: None declared, J. Askling Grant/research support: IMI BT-Cure Project DOI 10.1136/annrheumdis-2014-eular.3288

Background Since the introduction of biological disease-modifying antirheumatic drugs (bDMARDs), treatment of rheumatoid arthritis (RA) has changed. Remission is a feasible treatment target for many patients. As a result, there is an increased interest in appropriate treatment strategies after achieving disease control, such as bDMARD discontinuation while in remission. However, its adoption in typical clinical practice has not been widely studied. Objectives We conducted a cross-national longitudinal observational study of bDMARD to describe the proportions of RA patients in remission who discontinued these agents, and to assess the potential predictors of discontinuation. Methods We utilized data from US CORRONA and Japanese NinJa registries. Patients who used bDMARDs on at least two consecutive visits and experienced remission defined by the Clinical Disease Activity Index (CDAI) ≤2.8 at least once were included. The outcome of interest was bDMARD discontinuation while in remission. Discontinuation was described with the Kaplan-Meier method as well as the cumulative incidence function method to account for competing risk events, i.e., loss of remission and switch to another bDMARD. The baseline predictors of discontinuation were assessed in the Cox regression models. Results The numbers of eligible patients were 4,382 in the CORRONA (34.4% of 12,721 bDMARD users among 22,684 total patients) and 413 in the NinJa (18.4% of 2,243 bDMARD users among 11,205 total patients). In the Kaplan-Meier analysis, discontinuation at 5 years among patient who remained in remission was observed in 28.1% in CORRONA and 22.7% in NinJa (p=0.002, log-rank test; Figure Panels A and B). In the cumulative incidence function analysis, the proportions of discontinuation at 5 years among patients who were initially in remission were 11.3% in CORRONA and 12.2% in NinJa (Figure Panels C and D). It was not significantly different (p=0.782, Gray's test) due to greater attrition to loss of remission in CORRONA (83.9%) compared to NinJa (77.2%). In Cox regression, reduced CDAI (hazard ratio for 1 point decrease: 1.49 [1.37,1.61] in CORRONA and 1.79 [1.33,2.38] in NinJa) and use of glucocorticoids (HR: 1.59 [1.19,2.12] in CORRONA and 2.11 [1.03, 4.31] in NinJa) predicted higher rates of bDMARD discontinuation in both cohorts. The overall R2 for the full models including sex, race, age, RA duration, biologic class, methotrexate use, duration of bDMARD use, and index year, was 0.074 in CORRONA and 0.168 in NinJa. ![Figure][1] Conclusions We found a slightly higher rate of bDMARD discontinuation in CORRONA than NinJa. Possible contributors to the discrepancy may include health care system differences (e.g. out of pocket cost) as well as cultural differences (e.g. patient preference vs doctor recommendation). While several variables were associated with more frequent discontinuation, they did not provide robust explanation of the variability in practice. Acknowledgements We would like to thank all CORRONA and NinJa contributors (patients, clinicians, and investigators) for maintaining such valuable sources of information. The CORRONA RA registry has been supported through contracted subscriptions in the last two years by Abbvie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex and UCB. All non-pharmaceutically-initiated CORRONA research activities are conducted entirely independent of any pharmaceutical input. NinJa was supported in part by a Health and Labor Sciences Research Grant from the Ministry of Health, Labor, and Welfare of Japan. Disclosure of Interest : K. Yoshida Paid instructor for: Abbott Japan, H. Radner: None declared, M. Mjaavatten: None declared, J. Greenberg Shareholder of: CORRONA, Consultant for: AstraZeneca, Pfizer, Employee of: CORRONA, A. Kavanaugh Grant/research support: Abbott, Janssen, Amgen, BMS, Roche, UCBM, M. Kishimoto Speakers bureau: Santen, Mitsubishi-Tanabe, Pfizer, Abbott Japan, K. Matsui: None declared, M. Okada Speakers bureau: Santen, Mitsubishi-Tanabe, Pfizer, Abbott Japan, G. Reed Employee of: CORRONA, Y. Saeki Grant/research support: Tanabe-Mitsubishi, Chugai, Janssen, Nippon-Kayaku, Nichi-Iko, S. Tohma Grant/research support: Pfizer Japan, Eisai, Chugai, J. Kremer Shareholder of: CORRONA, Grant/research support: Abbott, Amgen, BMS, Genetech, Novo- Nordisk, Pfizer, Novartis, Eli Lilly, Employee of: CORRONA, D. Solomon Grant/research support: Eli Lilly, Amgen, CORRONA, Consultant for: Pfizer, Novartis, Eli Lilly DOI 10.1136/annrheumdis-2014-eular.1367 [1]: pending:yes

Background Remission has been proposed as the therapeutic target in RA. Physical function, on the other hand, is one of the major outcomes in RA predicting work disability, health care resource utilisation and mortality. It is currently still unclear what the minimum duration of remission is that would improve functional capacity to the best possible degree. Objectives To investigate the course of functional status assessed by health assessment questionnaire (HAQ) in RA patients with sustained clinical remission (REM) for at least 6 months. Methods We were provided a random 80-90% data sample of RA patients enrolled in recent clinical trials (ASPIRE, ATTRACT, DE019, ERA, Leflunomide, PREMIER, and TEMPO; n=4362) by the respective sponsors. We identified patients, who at some point during the trials achieved REM by the Disease Activity Score using 28 joint counts and C-reactive protein (DAS28-CRP ≤2.6) or Simplified Disease Activity Index (SDAI ≤3.3), and who maintained it in all subsequent visits throughout at least 6 months.We obtained HAQ scores during these 6 month REM periods, and were thus able to investigate the course of physical function over time in sustained REM using the Wilcoxon test. In additional analyses, patients with a HAQ=0 at REM entry were excluded as they had a priori no chance to show improvement during sustained REM. Results Out of 4362 patients we identified 605 patients in sustained remission by DAS28-CRP (mean duration of REM 38.8±25.1 weeks), and 385 patients by SDAI (mean duration 37.2±23.7 weeks). There were no significant differences in baseline characteristics between these two groups. A significant decrease of HAQ over time was found over the first 6 months in REM by DAS28-CRP (mean±SD HAQ monthly from baseline to month 6: 0.25±0.4 to 0.22±0.38 to 0.22±0.39 to 0.21±0.38 to 0.20±0.37 to 0.18±0.31 to 0.16±0.32) or SDAI (0.17±0.3 to 0.16±0.32 to 0.15±0.3 to 0.14±0.29 to 0.13±0.29 to 0.13±0.26 to 0.11±0.27) with significantly (p Conclusions Functional capacity is significantly improving when remission is reached, but continues to improve if remission is sustained. The stringency of the remission criteria determines how quickly patients in remission achieve their best possible functional improvement. Disclosure of Interest H. Radner: None Declared, F. Alasti: None Declared, J. Smolen Consultant for: Abbott, Amgen, Centocor, Pfizer and Sanofi, D. Aletaha Consultant for: Abbott, Amgen, Centocor, Pfizer and Sanofi

Background Several genes have been identified so far in the pathogenesis of rheumatoid arthritis (RA). The most important region is the Human Leukocyte Antigen (HLA) that contributes to approximately half of the genetic susceptibility for RA. The association seems to be stronger or specific for anti-citrullinated protein antibodies (ACPA) positive disease. More than 30 other variants in potentially pathogenic genes located in non-MHC regions have been identified by recently performed genome wide analysis studies among individuals of European ancestry. These alleles explain about 23% of the RA genetic burden. Objectives The aim of our study was to analyze the association of previously confirmed RA risk alleles in Slovak population and to determine their relationship and involvement in the increase of disease risk. Methods Genetic analysis was conducted in 1224 samples (494 RA patients, 728 controls; 83% females, 17% males) with balanced geographic distribution. The presence of HLA-DRB1 alleles (DRB1*04:01, 04:04, 04:05, 04:08, 04:10, 01:01, 01:02, 10:01) considered as shared epitope (SE) was analysed by ELPHA (Enzyme Linked Probe Hybridization Assay). Eight non-MHC single nucleotide polymorphysms (SNPs): PTPN22 (rs2476601), STAT4 (rs75744865), CTLA4 (rs3087243), PADI4 (rs2240340), AFF3 (rs11676922), IRF5 (rs10488631), TNFAIP3 (rs5029937) and TRAF1/C5 (rs3761847) were genotyped by real-time PCR using the TaqMan 5′-allele discrimination assay. Principal component analysis (PCA) followed by discrimination analysis were applied to reveal the relations between these genetic factors and disease. Results Our results show that of all genes analysed, the distribution of PTPN22, STAT4, IRF5 and PADI4 risk alleles and genotypes was significantly different between RA patients and healthy subjects in Slovak population (P Conclusions Genetic factors explain 11.1% of data variability in our cohort. The RA diagnose is significantly affected by presence of SE risk allele and RA associated alleles in genes STAT4, PTPN22, IRF5 and PADI4 with emphasis on heterozygozyty being sufficient to increase the risk of disease. Acknowledgements Study was supported by grants: ATMOS N00024, VEGA 2/0018/12, ITMS 26240220058 Disclosure of Interest None Declared

Objectives To correlate cartilage thickness as measured by ultrasound (US) with joint space narrowing (JSN) and joint space width (JSW) as measured by conventional radiography in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis. To validate US for measuring cartilage thickness, cadaver specimens of MCP joints were evaluated by US and by anatomical measurement. Methods Bilateral MCP 2-5 joints of 35 consecutive patients (280 joints) recruited in our outpatient clinic who had conventional radiographs ( Results In the patient population mean age was 63.1±11.3 years, mean disease duration was 10.6±7.8 years, mean CDAI was 8.1±7.3; 82.9% were female and 51% were rheumatoid factor positive. US measurement of MCT of MCP 2-5 was 0,42+/-0,19 mm. MCT of individual joints of the left and right hand correlated with individual MCP JSN (r=-0.799 and -0.702 respectively, p Conclusions Both JSW and JSN by radiography indeed represent cartilage thickness at least in MCP joints. US is a valid tool for measuring MCT. Phalangeal cartilage thickness has no added value beyond the measurement of MCT. When radiographic scoring is not available, US measurement of MCT might be a feasible alternative to depict cartilage damage in patients with RA. Disclosure of Interest None Declared

Background Rheumatoid factor (RF) and antibodies to citrullinated peptides (ACPA) are established markers in the diagnostic and prognostic approach to RA 1 . Several studies have examined changes of RF during therapy, but data for ACPA are controversial and scarce, and the effects of RA chronicity are still not completely understood 2 . Objectives To investigate the influence of treatment response and disease duration on RF and ACPA levels. Methods We obtained data of outpatients from a long-term observational database with prospective data entry. We retrieved clinical and serological data of patients treated with methotrexate, leflunomide and/or TNF inhibitors from the treatment start through six months of therapy. For analyses of the effects of treatment response and duration of RA, we calculated the SDAI 50% response at 6 months, and divided the patients into early (≤6 months duration) and established RA (>6 months). We used the Spearman test (r) to analyse correlations between changes in SDAI and changes in autoantibody levels. RF was determined by nephelometry (upper limit of normal [ULN] 14IU/ml) and ACPA by anti-CCP ELISA (ULN: 5U/ml). Only patients with complete datasets for the whole 6 months were selected. Results 96 RF and ACPA positive patients were included. Autoantibody levels declined significantly over the 6 months of therapy for both, RF (p=0.01) and ACPA (p=0.05). Treatment responders and patients with short disease duration showed the greatest changes (Table). There was no significant difference in the distribution of relative changes in RF and ACPA (p=0.99). Changes of SDAI correlated significantly with those of RF (r=0.32; p=0,01) and ACPA (r=0.25; p=0,05), particularly in early stages of RA (RF: r=0.52; p=0,05 and ACPA: r=0.59; p=0,01). Conclusions RF and ACPA levels decreased in line with the clinical response, especially at early stages of RA. Further research is needed to analyse the impact of early serological changes on the long-term outcome of RA. References Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM 2010;103(3):139-46. Bobbio-Pallavicini F, Caporali R, Alpini C, Moratti R, Montecucco C. Predictive value of antibodies to citrullinated peptides and rheumatoid factors in anti-TNF-alpha treated patients. Ann N Y Acad Sci 2007;1109:287-95. Aletaha D, Martinez-Avila J, Kvien T, Smolen J. Definition of Treatment Response in Rheumatoid Arthritis Based on the Simplified and the Clinical Disease Activity Index. [abstract]. Arthritis Rheum 2011;63 Suppl 10:2226. Disclosure of Interest None Declared

Background Progression of joint damage in RA occurs primarily in joints that are clinically swollen, and repair is seen only in joints with no clinical swelling. 1;2 On the other hand, joints exhibiting US but not clinical swelling may progress radiologically despite clinical remission. 3 This discrepancy requires elucidation to understand the value of clinical compared with US joint assessment, since except for histology, there is no true gold standard for US joint activity. Objectives To evaluate the differences in number of clinically and US active joints in RA, with special regards to the impact of US definitions of activity. Methods We performed US imaging of 22 joints of the hands of RA patients in clinical remission (CDAI≤2.8). Each joint was assessed for grey scale synovial hypertrophy (GSSH; 0=no hypertrophy; 1=hypertrophy) and power Doppler (PD) signal (0= no hyperaemia, 1= mild, 2=moderate, 3=marked). We investigated the sensitivity and specificity of clinically swollen joints (SJC) for presence of US changes and repeated this analysis using different cut points and combinations of US definitions. We further assessed changes of CDAI if clinical SJC were replaced by US active joints. Results Of the 58 patients in clinical remission, 96.6% had GSSH and 93.1% had positive PD signals. The sensitivity and specificity of clinical SJC for any US abnormality (GSSH>0 or PD>0) was 1.7% and 100%, respectively. When we used more stringent definitions of US activity (GSSH>0 & PD=3), these values changed to 22.2% and 99%. Replacing clinical by US counts in the calculation of CDAI, the US CDAI values approached the clinical CDAI with increasing stringency of the definition used (Fig.). In fact, the most stringent definition (GSSH>0 & PD=3) revealed identical average values as seen in the clinical CDAI. Conclusions Low PD signals increase the numbers of patients classified as having active joints and lead to a poor sensitivity of clinical assessment in comparison to US assessment. When the PD signal is combined with assessment of GSSH, or the strength of the PD signal is considered, the differences decrease, particularly when looking at their impact on composite indices. The relevance of this finding will have to be tested in relation to radiographic progression of joint damage. References Klarenbeek NB et al. ARD 2010; 69(12):2107-2113. Lukas C et al. ARD 2010; 69(5):851-855. Brown AK et al. Arthritis Rheum 2008; 58(10):2958-2967. Disclosure of Interest None Declared

Objective To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing (JSN) or width (JSW) in patients with rheumatoid arthritis (RA). Methods Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2–5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2–5 joints (n=19) were evaluated by anatomical measurement and US. Results The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=�0.32, p

Introduction To investigate the course of functional status assessed by health assessment questionnaire (HAQ) in rheumatoid arthritis (RA) patients with sustained clinical remission (REM). Methods In recent RA clinical trials, we identified patients with subsequent visits of ≥24 weeks in clinical REM according to the disease activity score using 28-joint counts including C-reactive protein (DAS28) (≤2.6), or simplified disease activity index (SDAI) (≤3.3). Area under the curve (AUC) and mean HAQ scores throughout the time in sustained REM were compared using t test, analyses of variance (ANOVA) and adjusted general linear modeling (GLM) with repeated measures. In Cox regression analyses, the time to regain full physical function was modeled. Sensitivity analyses were performed in patients of sustained SDAI low disease activity (LDA; SDAI ≤11). Results A total of 610 out of 4364 patients achieved sustained DAS28 REM (14 %) and 252 SDAI REM (5.8 %). ANOVA testing for linear trend showed significant decrease of mean HAQ from week 0 (start of REM) to week 24, regardless of REM criteria used. AUC of HAQ throughout 24 weeks of REM was higher in DAS28 compared to SDAI REM (p ≤0.01). GLM adjusting for covariates showed significant decrease of monthly HAQ scores from week 0 to 24 (DAS28: 0.276, 0.243, 0.229, 0.222, 0.219, 0.209 to 0.199; p = 0.0001; SDAI: 0.147, 0.142, 0.149, 0.129, 0.123, 0.117 to 0.114; p = 0.029). Similarly, a decrease of HAQ over time was found in patients of sustained SDAI LDA. In DAS28 REM, the chance of regaining full physical function was higher for female (hazard ratio HR [95 % confidence interval]: 1.41 [1.13–1.76]) and early RA patients (disease duration ≤2 years: HR 1.29 [1.01–1.65]); in SDAI REM no significant differences were found. Conclusions Physical function continues to improve if the target of REM or LDA is sustained. The stringency of the remission criteria determines achievement of the best possible functional improvement. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0719-x) contains supplementary material, which is available to authorized users.

Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes a considerable burden for the patient and society. It is not clear yet whether aiming for remission (REM) is worthwhile, especially when compared with low disease activity (LDA). Methods In 356 consecutive RA patients, we obtained data on physical function (health assessment questionnaire (HAQ)), health-related quality of life (HRQoL: Short Form 36 (SF36), Short Form 6 dimensions (SF-6D), Euro QoL 5D (EQ-5D)), work productivity (work productivity and activity impairment questionnaire (WPAI)), as well as estimation of direct and indirect costs. Cross-sectionally, data were compared in patients within different levels of disease activity according to the simplified disease activity index (SDAI; remission (REM ≤3.3); n = 87; low disease activity (LDA: 3.3 11 n = 119) by using analyses of variance (ANOVA). Longitudinal investigations assessed patients who changed from LDA to REM and vice versa. Results We found differences in patients achieving REM compared with LDA for HAQ (0.39 ± 0.58 versus 0.72 ± 68), WPAI (percentage impairment while working 11.8% ± 18.7% versus 26.8% ± 23.9%; percentage of overall activity impairment, 10.8% ± 14.1% versus 29.0% ± 23.6%)), EQ-5D (0.89 ± 0.12 versus 0.78 ± 0.6) and SF-36 (physical component score (PCS): 46.0 ± 8.6 versus 38.3 ± 10.5; mental component score (MCS): 49.9 ± 11.1 versus 47.9 ± 12.3) (P

Introduction To determine the validity and reliability of patients' self-performed joint counts compared to joint counts by professional assessors in rheumatoid arthritis (RA) patients in different disease activity states. Methods In patients with established RA we determined the inter-rater reliability of joint counts performed by an independent evaluator and the patient using intraclass correlation (ICC), and agreement on activity in individual joints by kappa statistics. We also performed longitudinal analyses to assess consistency of assessments over time. Finally, we investigated the concordance of joint counts of different assessors in patients with different levels of disease activity. Results The reliability of patient self-performed joint counts was high when compared to independent objective assessment (ICC; 95%confidence interval (CI)) for the assessment of swelling (0.32; 0.15 to 0.46) and tenderness (0.75; 0.66 to 0.81), with higher agreement for larger joints (kappa: 0.57 and 0.45, respectively) compared to smaller joints (metacarpo-phalangeal joint (MCPs): 0.31 and 0.45; and proximal interphalangeal joint (PIPs): 0.22 and 0.47, for swelling and tenderness, respectively). Patients in remission according to the Simplified Disease Activity Index (SDAI ≤ 3.3) showed better concordance of the joint counts (swollen joint count (SJC) ties 25/37, tender joint count (TJC) ties 26/37) compared to moderate/high disease activity states (SDAI > 11; MDA/HDA: SJC ties 9/72, TJC ties 21/72). Positive and negative predictive values regarding the presence of SDAI remission were reasonably good (0.86 and 0.95, respectively). A separate training session for patients did not improve the reliability of joint assessment. The results were consistent in the longitudinal analyses. Conclusions Self-performed joint counts are particularly useful for monitoring in patients having attained remission, as these patients seem able to detect state of remission.