Years In Rheumatoid Arthritis Patients Research Articles

Comparison of romosozumab versus denosumab treatment on bone mineral density after 1 year in rheumatoid arthritis patients with severe osteoporosis: A randomized clinical pilot study.

To investigate the effect of romosozumab versus denosumab treatment on bone mineral density (BMD), disease activity, and joint damage in patients with rheumatoid arthritis and severe osteoporosis. Fifty-one postmenopausal women were enrolled and randomized equally into two groups to receive either romosozumab or the denosumab. Changes (Δ) in the BMD (at lumbar spine, total hip, and femoral neck), disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and van der Heijde-modified Total Sharp Score (TSS) from baseline to 12 months after treatment were evaluated. The ΔBMD at 12 months in the romosozumab and denosumab groups were 10.2 ± 5.6% and 5.0 ± 3.1% (p = .002) for the lumbar spine, 3.7 ± 4.9% and 3.5 ± 3.0% (p = .902) for the total hip, and 3.6 ± 4.7% and 3.2 ± 4.9% (p = .817) for the femoral neck, respectively. The ΔDAS28-ESR and ΔTSS at 12 months did not differ between these two groups. Our results suggest that romosozumab treatment was more effective in increasing the BMD at the lumbar spine than denosumab and may be selected for patients who require a significant increase in the lumbar spine BMD.

Incidence of new carotid plaques in rheumatoid arthritis patients: 6-Year prospective results of the TOMORROW study.

The purpose of this study was to evaluate the new incidence of carotid plaques in rheumatoid arthritis (RA) patients over a 6-year prospective follow-up and to assess the risk factors. This is a 10-year prospective cohort study that included 208 RA patients and 205 age- and gender-matched controls. Ultrasound assessment of the bilateral carotid arteries was performed in 2011 and 2017. There were no differences in the incidence of new carotid atherosclerotic plaques over 6 years between the two groups (35.5% vs. 37.0%, respectively; p = .936). The mean Disease Activity Score 28-C-reactive protein over 6 years in RA patients was 2.73 ± 0.95. Multiple logistic regression analysis showed that RA was not a risk factor for new carotid atherosclerotic plaques (odds ratios, 0.708; 95% confidence interval, 0.348-1.440; p = .340). An average glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques (odds ratios, 8.54; 95% confidence interval, 1.641-44.455; p = .011). Incidence of new carotid atherosclerotic plaques was similar between well-controlled disease activity RA patients and control subjects. A mean glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques.

P282 ANA seroconversion during prior anti-TNF therapy abolishes anti-CCP antibody positivity as a predictor of abatacept retention in rheumatoid arthritis

Abstract Background/Aims Few long-term drug survival analyses have been reported for patients with rheumatoid arthritis (RA) treated with abatacept. Here we report a machine learning approach to investigate drug-survival of abatacept over 5 years in RA patients. Methods We performed a retrospective observational study on a tertiary hospital dataset of RA patients who started abatacept between January 2008 and December 2020. Time to abatacept discontinuation over 5 years was estimated using Kaplan-Meier survival analyses. A multivariate cox-proportional hazard model to predict abatacept discontinuation was chosen by random survival forest and partial least regression. Results A total of 112 RA patients (81% female, mean age 58.1 [SD 13.5] years) received abatacept. Mean disease duration was 18.3 months (SD 13.6). More than half (65/112) were co-prescribed at least one conventional synthetic DMARD (csDMARD). Methotrexate was the most frequently concomitant csDMARD (n = 37), followed by hydroxychloroquine (n = 23), sulfasalazine (n = 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (intermittent or continuous) with abatacept. Abatacept was mostly used as 4th (n = 29) and 3rd line (n = 24) bDMARD, but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive (≥1:80) in 25 patients (pre-biologics) and 18 seroconverted to previously exposed anti-TNF (ANA seroconversion group). Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years. Multivariate cox-proportional hazard model revealed that ACPA positivity was associated with reduced risk of abatacept discontinuation with HR of 0.56 (95% CI 0.32-0.95,p=0.03) compared to the ACPA-negative group. In contrast, the ANA seroconversion group demonstrated worse retention of abatacept with HR of 2.67 (95% CI 1.39-5.16, p = 0.0033) compared to ANA-negative patients. Kaplan-Meier analysis demonstrated that in the ANA seroconversion group, retention of abatacept was significantly inferior to pre-anti-TNF ANA positive patients (p = 0.0084) and ANA-negative patients (p = 0.0041). ACPA positivity was associated with better survival only in the non-ANA seroconverted group with HR of 0.54 (95% CI 0.29-0.92, p = 0.041), after adjusted by propensity score. Combining abatacept with any csDMARDs reduced the risk of abatacept discontinuation with HR of 0.57 (95% CI 0.33-0.98, p = 0.043) after adjusting by propensity score. No statistical difference was found between first-line, second-line, or any subsequent chronology of use of abatacept. Conclusion Our data suggest that previous ANA seroconversion occurring whilst on anti-TNF therapy reduces subsequent abatacept retention and cancels out the protective effect of anti-CCP positivity. The mechanism through which this occurs is unclear and further prospective and mechanistic studies are needed to validate these findings. Disclosure J. Kimpton: None. M. Shipa: Grants/research support; MS is funded by Versus Arthritis. S. Yeoh: Grants/research support; SY is funded by the Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities, and Versus Arthritis. E. Hawkins: None. M. Ehrenstein: Grants/research support; ME is supported (in part) by the University College London Hospital Biomedical Research Centre.

Total Hip Replacement in Patients with Rheumatoid Arthritis: Trends in Incidence and Complication Rates Over 35Years.

IntroductionAdvances in rheumatoid arthritis (RA) management have made disease remission achievable. We evaluated trends in total hip replacement (THR) and postoperative outcomes in patients with RA in Western Australia (WA) over more than three decades.MethodsThis was a retrospective analysis of routinely collected prospective data from a state-wide registry containing longitudinally linked administrative health data based on International Classification of Diseases (ICD) diagnostic and procedural codes. We included patients with two or more diagnostic codes for RA (between 1980 and 2015) and studied THR incidence rates (THR IR) and complication rates (revision, peri-prosthetic fracture, infection, venous thrombosis, and mechanical loosening). Survival rates were estimated by Kaplan–Meier method and predictors analyzed by Cox regression.ResultsWe followed 9201 RA patients over 111,625 person-years, during which 1560 patients (16.9%) underwent THR. From 1985 to 2015, THR IR (per 1000 RA patient-years) decreased from 20.8 (95% CI 20.1–21.5) to 7.3 (95% CI 7.2–7.5), and 5-year THR-free survival increased from 84.3 to 95.3% (1980–2015). Ten-year prosthetic survival was 91.2%. Complication rates in the first 5 years post-THR decreased significantly from 13.1 to 3.7% (p < 0.001). Mechanical complications such as loosening and periprosthetic fracture rates decreased significantly (> 35%, P < 0.05), while infection and revision did not change over the observation period (p > 0.05).ConclusionsOver the last 30 years in RA patients, THR IR and mechanical complication rates decreased significantly, but the medical complication of infection has not changed significantly.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00414-9.

Hypothyroidism risk associated with rheumatoid arthritis: A population-based retrospective cohort study.

Studies on the thyroid disease risk in patients with rheumatoid arthritis (RA) associated with comorbidities are limited. This population-based retrospective cohort study investigated the hypothyroidism risk in patients with RA and the role of comorbidities.We used Taiwan National Health Insurance Research Database to identify 16,714 RA patients newly diagnosed in 2000 to 2008 and 66,856 control persons without RA, frequency matched by sex, age, and index year. Incidence and the RA group to controls hazard ratio of hypothyroidism were estimated.The hypothyroidism incidence was 1.74-fold higher in the RA group than in controls (16.6 vs 9.52 per 10,000 person–years), with the Cox method estimated adjusted hazard ratio of 1.67 (95% confidence interval = 1.39–2.00) after controlling for covariates. Near 75% of the study population were women, with the incidence 3.6-time higher than men in both groups. The hypothyroidism incidence increased with age, from 12.1 per 1000 person–years in 20 to 39 years to 20.0 per 1000 person–years in 60+ years in RA patients, higher than that in controls (7.17 vs 10.0 per 1000 person–years, respectively by age). Each comorbidity was related to an increased incidence and higher in the RA group than in controls. Among all comorbidities, stroke exerted the greatest impact in the RA group with an adjusted hazard ratio of 3.85 (95% confidence interval = 1.24–12.0).RA patients have an increased risk of developing hypothyroidism; this risk was pronounced in women and the elderly. RA patients should be closely monitored to prevent the development of hypothyroidism.

Periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs in rheumatoid arthritis: A 1-year follow-up study.

To assess whether periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) for 1 year in rheumatoid arthritis (RA) patients. Data were collected from 50 RA patients who had received corticosteroids, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 1 year of bDMARD therapy in a retrospective study. Rheumatologic conditions were compared between the two periodontitis severity groups according to the periodontal inflamed surface area (PISA) or Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) case definitions. Twenty-eight patients with no or mild periodontitis showed significantly greater decreases in changes in Clinical Disease Activity Index (CDAI) and tender and swollen joint count in comparison to 22 patients with moderate and severe periodontitis (p = .02, p = .01, and p = .03). Both bivariate and multivariate analyses revealed a significantly positive association between the baseline CDC/AAP definitions and CDAI changes (p = .005 and p = .0038). However, rheumatologic conditions were comparable between 25 patients each in the low and high PISA groups. Baseline periodontitis severity according to the CDC/AAP definitions is associated with the clinical response to bDMARDs for 1 year in RA patients.

THU0101 IMPACT OF TREATMENTS ON RADIOGRAPHIC PROGRESSION OVER THE FIRST 10 YEARS OF DISEASE IN EARLY RHEUMATOID ARTHRITIS: RESULTS FROM THE ESPOIR COHORT

Background:Long-term observational studies on the prediction of structural damage progression (SDP) in rheumatoid arthritis (RA) have mostly considered patients baseline characteristics and have rarely evaluated the specific impact of treatments in real world settings.Objectives:To assess the impact of treatments exposure on the 10-year radiographic progression in early rheumatoid arthritis (RA).Methods:The 310 patients of the ESPOIR cohort fulfilling ACR/EULAR 2010 criteria at baseline and having complete radiographic data at baseline and 10 years were considered in the present study. SDP was defined at 10 years as a significant increase of the Sharp/van der Heijde score, i.e., superior to the Smallest Detectable Change of 11.5 at 10 years. Three RA treatments were considered: glucocorticoids (GC), conventional synthetic and biologic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs and bDMARDs), which posologies were standardized by the mean of dose quotients (DoseQ). Drug exposure was modelled with Weighted Cumulative Exposure (WCE) variables, considering the intensity of drug exposure defined as a weighted function of past doses, and was incorporated into a logistic regression model that also included baseline clinical, biological and radiological characteristics. The predictive performance of this WCE model was compared to models considering on the one hand only baseline characteristics (BSL model) and on the other, baseline characteristics and binary treatments exposure - in other terms, “ever exposed, yes or no” (BIT model).Results:Overall, SDP at 10 years occurred in 85 (27.4%) patients. GC exposure was significantly associated with SDP in univariate analysis only, and therefore was not included in the final WCE model. In the final WCE model, the joint exposure to 1 DoseQ of csDMARD and 1 DoseQ of bDMARD during the 10-year follow-up was associated with a significant protective effect on SDP compared to patients receiving no treatment: OR=0.04 (95% CI: 0.002-0.72). Early csDMARD initiation was associated with a significantly lower risk of SDP compared to later initiation (Table 1).Table 1.odd ratios for the association of patterns of drug regimen with 10-year radiographic progressionExposure testedReferenceOR (95%CI)Treatments intakes during the last 10 yearscsDMARD &amp; bDMARD for last 10 yearsNo treatment for last 10 years0.04 (0.002-0.72)Testing the interest of an early initiation of csDMARDs (not combined with bDMARD)csDMARD for last 10 yearscsDMARD after month 30.79 (0.65-0.96)csDMARD after month 60.41 (0.19-0.86)csDMARD after year 10.13 (0.02-0.80)Testing the interest of an early initiation of bDMARDs (in association with csDMARD)bDMARD after month 3No treatment for last 10 years0.04 (0.002-0.72)bDMARD after month 60.04 (0.002-0.72)bDMARD after year 10.04 (0.002-0.72)bDMARD after year 20.04 (0.003-0.73)bDMARD after year 30.05 (0.03-0.81)Initiation of a bDMARD between the 3rd month and 3rd year of follow-up in combination with a csDMARD was significantly associated with a lower risk of SDP compared to no bDMARD treatment (Table 1).The final WCE model was better at predicting SDP at 10 years compared to the BSL and BIT models, with AUC=0.92 (95% CI: 0.89-0.95) (Figure 1).Figure 1.ROC curves of BSL model (A), BIT model (B) and WCE combined model (C) for 10-year radiographic progressionConclusion:CsDMARDs and bDMARDs have a protective effect on radiographic progression at 10 years in RA patients. This study has shown the value of considering drug exposure in the study of RA prognosis, and modeling this exposure using WCE variables.Disclosure of Interests:Joanna KEDRA: None declared, David Hajage: None declared, Alexandre Lafourcade: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp &amp; Dohme; Pfizer; Roche-Chugai; UCB, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB

Glucocorticoid use is an independent risk factor for developing sarcopenia in patients with rheumatoid arthritis: from the CHIKARA study.

Patients with rheumatoid arthritis (RA) are at higher risk of sarcopenia because of joint dysfunction and chronic inflammation. The present study aimed to investigate the predictors or risk factors for developing sarcopenia in RA patients using the prospective observational CHIKARA database. We hypothesized that older age, higher disease activity, lower physical function, and glucocorticoid (GC) use are risk factors for sarcopenia. A total of 100 consecutive RA patients participated in the CHIKARA study. Their body compositions were examined using a body composition analyzer. Laboratory data, disease activity, physical function, and treatment were investigated. Sarcopenia was assessed at baseline and at 1year. Predictors or risk factors for sarcopenia development at 1year were investigated by univariate and multivariate analyses. Of 68 patients without sarcopenia at baseline, 9 (13.4%) developed sarcopenia over the year. Univariate analysis showed that age (r = 0.28, p = 0.022), average GC dose over the year (r = 0.25, p = 0.043), and body mass index (r = - 0.28, p = 0.019) were significantly associated with the development of sarcopenia. Average GC use at ≥ 3.25mg/day was a significant factor on multivariate analysis (odds ratio 8.81, 95% confidence interval 1.14-67.9, p = 0.037). RA patients using GCs at an average dose ≥ 3.25mg/day over 1year were at higher risk for developing sarcopenia. Reduction or withdrawal of GCs may prevent sarcopenia.Key Points• Patients with RA are at higher risk of sarcopenia.• Predictors or risk factors for developing sarcopenia over 1 year in RA patients were investigated using the prospective observational CHIKARA database.• RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia.• Reduction or withdrawal of GCs may be essential to prevent sarcopenia.

Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

BackgroundUnited Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA.MethodsThe study included biologic-naïve patients receiving csDMARDs only with MDA (3.2 <DAS28≤ 5.1) when recruited to the control cohort of the British Society for Rheumatology Biologics Register–RA (BSRBR-RA). Disability scores, measured using the Health Assessment Questionnaire (HAQ), were recorded every six months for three years. Trajectories of HAQ scores over follow-up were assessed using latent class growth models (LCGMs). Baseline age, gender, DAS28, symptom duration, rheumatoid factor status, number of prior csDMARDs and co-morbidities were assessed as potential predictors of group membership.ResultsIn total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group.ConclusionThere is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy.

Comparative evaluation of denosumab efficacy of in patients with rheumatoid arthritis and postmenopausal osteoporosis: results of 1-year study in clinical practice

Objective: to assess bone mineral density (BMD) changes in rheumatoid arthritis (RA) patients with osteoporosis (OP) and in women with postmenopausal OP during therapy with denosumab (DSB) for 1 yearSubjects and methods. 121 women were included: the main group – 69 patients with RA (mean age – 60±7 years), 34 (49.3%) from them received glucocorticoids (GC). Comparison group comprised 52 women with primary OP (mean age – 62±10 years). Measurement of BMD using dual-energy X-ray absorptiometry (DXA) was performed in the lumbar spine (LI–IV), femoral neck (FN), proximal femur as a whole (PF) and distal forearm (DF). DSB was administered subcutaneously at a dose of 60 mg 1 time in 6 months.Results and discussion. In patients with RA, the average increase of BMD for 12 months of treatment was: in LI–IV – 4.6%, in FN-2.8%, in PF-3.0% and in DF-0.7%, and in the comparison group – 5.2; 2.1; 2.9 and 0.9%, respectively. There were no significant differences of BMD changes between the groups. Efficacy of DSB therapy in RA patients with OP did not depend on RA activity, duration of GC therapy and cumulative dose of GC. Adverse events that did not lead to the withdrawal of the drug were noted in 3% of the study participants. There were no fractures during the observation.Conclusion. The efficacy treatment with DSB for 1 year in RA patients with OP and in women with postmenopausal OP is comparable. The use of GC did not have a negative impact on DSB effect.

Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population

BackgroundPatients with rheumatoid arthritis (RA) have increased risk of heart failure with preserved ejection fraction. The development and progression of left ventricular dysfunction before onset of clinical heart failure are unknown. The objective of this study was to evaluate longitudinal changes in cardiac structure and function of patients with RA compared with persons in the general population. MethodsA prospective longitudinal study of a population-based cohort of 160 patients with RA and a population-based cohort of 1391 persons without RA (non-RA cohort) was performed. Each participant underwent 2-dimensional, pulsed-wave tissue Doppler echocardiography at baseline and after 4 to 5years of follow-up. Age- and sex-adjusted linear regression models were used to test for differences between the RA and non-RA cohorts in annualized rates of change for echocardiographic parameters. ResultsMitral A velocity increased more rapidly among the patients with RA than the non-RA cohort (age- and sex-adjusted parameter estimate, 0.030; P<0.001). Correspondingly, the mean mitral inflow E/A ratio decreased faster in the RA cohort than the non-RA cohort (adjusted parameter estimate, −0.096; P<0.001). The left atrial volume index increased at a higher rate in the RA cohort than the non-RA cohort (adjusted parameter estimate, 0.150; P<0.001). ConclusionsThis pattern of echocardiographic findings confirms previous cross-sectional studies and indicates that subclinical changes in diastolic function occur more rapidly over 5years in RA patients than in the general population. Further research into the mechanisms of myocardial disease in these patients and the relationship with disease activity and treatment is warranted.

Early clinical response predicts low disease activity at one year in rheumatoid arthritis patients on treatment with certolizumab in real-life settings. An appraisal of the Italian registry GISEA

ObjectivesThe aim of this study was to assess whether good EULAR response assessed at 3months may predict the achievement of low disease activity (LDA) at 1year in rheumatoid arthritis (RA) patients on treatment with certolizumab pegol (CZP). MethodsFrom the nationwide Italian registry, we analysed 278 RA patients (age 54.8±12years, duration of disease 9.8±8years, female 84%) initiating CZP as first line (68%) or≥second line (32%) of biological treatment because of their active disease. Assessment of disease activity was based on 28 joint Disease Activity Score (DAS28). A reduction of DAS28>1.2 (good EULAR response) was assessed at 3months, and the achievement of LDA (DAS28≤3.2) was evaluated at 1year. Multiple regression models were used to estimate predictors of early good EULAR response or LDA. ResultsThe percentages of patients attaining good EULAR response were 52% at 3, 65% at 6, and 66% at 12months. Furthermore, 51.2% (98/192) of the patients reached LDA at 12months. Patients taking CZP as first biological treatment had adjusted odds ratios (OR) of good EULAR response at 3months 6 folds higher than in those with≥1 prior biological drug (OR 6.7, 95% CI 1.97–23.1). While, the strongest variable correlating with 12months LDA was the achievement of good EULAR response at 3months (OR 11.3, 95% CI 13.1–34.8). ConclusionsOur findings showed that attaining good EULAR response at 3months strongly predicted 1year LDA in RA patients treated with CZP in real-life settings.

Towards a stratified targeted approach with biologic treatments in rheumatoid arthritis: role of synovial pathobiology.

Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease affecting diarthrodial joints and extra-articular tissues; in the absence of an effective treatment, it is characterized by persistent symmetrical and erosive synovitis which leads to structural joint damage and lifelong disability. Several autoantibodies have been associated with RA such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). B cells have been shown to play a crucial role in the pathogenesis of RA by producing autoantibodies and promoting synovial inflammation through antigen presentation, T cells activation and cytokines production [1]. Although biologic agents have notably improved disease outcome and patients' quality of life, currently around 30-40% of subjects do not respond to treatment and the mechanisms leading to resistance are still not known [2]. For this reason, new prognostic biomarkers and predictors of response are needed. We and others have postulated that the development of biomarkers for patients' stratification prior therapeutic intervention may be possible through a better understanding of the different histopathological patterns present both in early and established individual RA patient and the related underlying cellular and molecular mechanisms. To date, Tumor Necrosis Factor (TNF)-α has been shown to be one of the master elements of inflammation in RA; however, even though therapies aimed at blocking this key cytokine have emerged as a major tool in the treatment of RA, a large proportion of patients (approximately 30-40%) do not achieve a meaningful clinical response assessed by either the American College of Rheumatology (ACR) or the European League Against Rheumatism (EULAR) criteria. The same limitation can be applied to the use of rituximab, a chimeric monoclonal antibody directed against CD20, which is uniquely expressed by all B-lymphocytes during the maturation process from late stage pro-B cells to memory cells. The clinical efficacy of rituximab has been proved by several clinical studies [3] but it is highly variable. Currently, NICE guidelines recommend rituximab in patients with inadequate response to a first-line biologic therapy, including at least one anti-TNFα agent independently of their pre-treatment chance to respond. In all cases, whether considering biologics used for several years in RA patients (anti-TNFα or rituximab) or relatively newer biologics in clinical use (i.e. tocilizumab, an anti-interleukin (IL) -6 receptor blocking monoclonal antibody or abatacept, a CTLA4 inhibitor fusion protein designed to target the T cell co-stimulatory signal mediated through the CD28-CD80/86 pathway), no validated biomarkers predictive of clinical response currently exist. Consequently, to date a "trial-and-error" approach is used in the prescription of biologics in RA, which has the obvious disadvantage of potentially exposing patients to drugs that they may not respond, with potential unnecessary side-effects, delaying use of an effective treatment and causing a significant economic burden to society. Therefore, identifying pre-treatment predictors of response with a customized stratification approach would be of invaluable importance in RA, also in consideration of the large number of biologics in development targeting novel pathways currently being tested in clinical trials. In this manuscript, we review existing data and provide future perspectives with regard to the role of synovial histopathology as a potential prognostic biomarker for patient stratification in RA, in particular regarding the use of specific biologic therapies.

Prevalence and concordance of early and sustained remission assessed by various validated indices in the early arthritis “ESPOIR” cohort

ObjectivesTo assess the prevalence of remission in early arthritis, to evaluate the concordance across different criteria sets in defining this state, and to look for predictive factors for early and sustained remission. MethodsPatients from the ESPOIR cohort were followed-up every 6months. We analysed early remission and sustained remission in 3 groups of patients: patients having rheumatoid arthritis (RA) according to 2010 ACR/EULAR criteria, undifferentiated arthritis (UA), and the whole cohort. Remission was defined according to ACR/EULAR criteria, 28 Joint Disease Activity Score (DAS28<2.6), and Simplified Disease Activity Index (SDAI≤3.3). Agreement was evaluated by k-coefficient. Predictive factors for sustained remission at 1, 3 and 5year in RA patients were analyzed. ResultsEight hundred and nineteen patients were included. Early remission rates in the RA/UA/ESPOIR groups were observed in respectively 29.2% (181/682), 51.4% (55/123) and 32.7% (239/813) of patients by DAS28; 15.7%, 29.1% and 18% by SDAI; and 11.2%, 29.1% and 12.8% by ACR/EULAR criteria. Agreement between classifications of remission was low for DAS28 vs. ACR/EULAR (k=0.44), high for SDAI vs. ACR/EULAR (k=0.78), and moderate for SDAI vs. DAS28 (k=0.54). Lower baseline disease activity scores, non-menopausal status and younger age were the best predictive factors for sustained remission, with consistent results across the 3 definitions of remission. ConclusionOur study showed that the rate of early and sustained remission in early arthritis is dependent on the definition used, with a variable degree of agreement across criteria sets, but with consistent predictive factors of favourable outcome in patients finally diagnosed with RA.

FRI0082 Development of impairment, disability, radiological damage, comorbidity and mortality over 20 years in rheumatoid arthritis patients

ObjectivesTo study the development of impairment, disability, radiological damage, comorbidity and mortality over 20 years in a cohort followed prospectively from diagnosis.Methods183 RA patients diagnosed between 1985 and 1989 were...

AB0304 Predictors of gain in quality adjusted life years in RA patients treated with biologics for one year

BackgroundThe Quality Adjusted Life Year (QALY), based on health-related quality of life measures such as euroqol 5 dimensions (EQ-5D), is an important outcome in rheumatoid arthritis (RA) studies, as it...

SAT0086 Extent of Atherosclerosis is Associated with Biomarkers for Unstable Plaques: A Prospective Study Over Five Years in Rheumatoid Arthritis Patients and Matched Controls

BackgroundIn the general population several serological biomarkers, for example phospholipase A2 group 7 (PLA2G7), macrophage inhibitory cytokine 1 (MIC-1), soluble CD40 ligand (sCD40L), myeloperoxidase (MPO) and interleukin 18 (IL-18), have...

Timing and Magnitude of Initial Change in Disease Activity Score 28 Predicts the Likelihood of Achieving Low Disease Activity at 1 Year in Rheumatoid Arthritis Patients Treated with Certolizumab Pegol: A Post-hoc Analysis of the RAPID 1 Trial

To determine the relationship between timing and magnitude of Disease Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not reached) during the first 12 weeks of treatment with certolizumab pegol (CZP) plus methotrexate, and the likelihood of achieving low disease activity (LDA) at 1 year in patients with rheumatoid arthritis. In a post-hoc analysis of the RAPID 1 study, patients achieving LDA [DAS28(ESR) ≤ 3.2] at Year 1 were assessed according to DAS28 nonresponse at various timepoints within the first 12 weeks. Seven-hundred eighty-three patients were included (CZP 200 mg, n = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group had a DAS28 improvement of ≥ 1.2 by Week 12. Of the 13.1% of patients with DAS28 improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA at Year 1 depended on timing of nonresponse - 22.3%, 8.4%, and 2.0% of patients with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year 1 - and magnitude of initial lack of DAS28 improvement; for example, compared with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6 had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively). Failure to achieve improvement in DAS28 within the first 12 weeks of therapy was predictive of a low probability of achieving LDA at Year 1. Moreover, the accuracy of the prediction was found to be strongly dependent on the magnitude and timing of the lack of the response. (Clinical Trial Registration Nos. NCT00152386 and NCT00175877).

Risk of atrial fibrillation and stroke in rheumatoid arthritis: Danish nationwide cohort study

Objectives To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.Design Longitudinal nationwide register based cohort study.Setting Inpatient and outpatient hospital care in Denmark from...

Persistent low grade synovitis without erosive progression in magnetic resonance imaging of rheumatoid arthritis patients treated with infliximab over 1 year

Disease remission is only reached by a minority of rheumatoid arthritis (RA) patients treated with infliximab. Radiological assessment reported in clinical trials support the view that even under persistent inflammatory activity there is no further structural damage. Magnetic resonance imaging (MRI) allows a highly accurate detection of synovitis, bone edema, and erosions, constituting the ideal instrument for the evaluation of treatment response. The goal of this study was to evaluate MRI changes over 1 year in RA patients treated with infliximab. Four RA patients refractory to methotrexate (MTX) therapy were treated with infliximab 3 mg/kg 8/8 weeks and followed up for 1 year. Disease Activity Score (DAS28) was measured in the day of each infliximab administration. MRI was performed at baseline, 3 months, and 1 year. A simplified OMERACT RA MRI scoring (RAMRIS) was applied to the dominant wrist: synovitis (0-3) was measured in the intercarpal-carpometacarpal joints (CMTJ); bone edema (0-39) and erosions (0-130) in the base of the metacarpal and wrist bones. Baseline DAS28 was superior to 3.2 in all patients (ranging from 4.8 up to 6.2). At 14 weeks, DAS28 was still superior to 3.2 (ranging from 3.5 up to 4.6) and at 46 weeks all patients have responded, however without having achieved clinical remission, as DAS28 was still above 2.6 (ranging from 2.6 up to 3.4). MRI showed that synovitis was reduced in all patients to a score of 1, bone edema was slightly reduced (10% reduction), and erosive score was unchanged (baseline values ranging from 2 up to 20). Despite persistent low disease activity, these four RA patients treated with infliximab had stable simplified RAMRIS erosive scores over 1 year. These results support the view that there might be an uncoupling process between inflammation and bone erosions when tumor necrosis factor alpha is targeted in RA.