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Objective:To validate a model which predicts progression from undifferentiated arthritis (UA) to RA, in a Canadian UA cohort.Methods:The prediction rule, comprising variables which are scored from 0 to 13, with higher scores reflecting an increased risk of RA, was applied to baseline characteristics of all patients with UA. Progression to RA was determined at 6 months.Results:105 patients were identified. By 6 months, 80 (76%) had developed RA while 25 (24%) had developed another diagnosis. Number of tender and swollen joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide positivity, poor functional status and high disease activity were associated with development of RA (pConclusions:High scores in our cohort predicted those who progressed to RA by 6 months. Baseline scores ⩾8 corresponded with higher rates of progression.

Biologics have changed expectation and outcomes for rheumatoid arthritis (RA). However, the optimal duration and sequence of therapy for this disease has yet to be determined. Also, a significant number of patients do not satisfactorily respond to currently available therapies. The Janus kinase (JAK) inhibitors represent a new class of therapies for RA. These drugs work uniquely by inhibiting intracellular pathways thought to be important in the pathogenesis of RA. They are available as oral agents, which is also different from the currently available biologics. Baricitinib has now been evaluated in four phase III clinical trials, and although safety concerns cannot fully be answered until the drug is studied over longer periods of time, the data to date suggest that this drug with its once daily dosing, rapid onset of action and efficacy as monotherapy represents an important addition to the RA therapeutic armamentarium. Further study and experience will better define how baricitinib will be used and by which patients.

A 61-year-old woman of Italian descent with a history of hypertension and gastroesophageal reflux disease presented to the emergency department with a two-week history of pain, erythema, swelling and restricted range of motion of her left ankle. The patient was prescribed cephalexin for possible

This conference report describes six presentations that were given during a Canadian Institutes for Health Research-funded workshop. The goal of the workshop was to discuss key knowledge gaps in the study of outcomes in mothers with rheumatic diseases and their offspring. Presentations focused on epidemiological and methodological issues associated with the reproductive and perinatal health of women with rheumatic diseases. Discussions of relevant recent research allowed for discovery of potential data sources that could facilitate interdisciplinary research and created the opportunity for future collaborations.

Objective.To develop a list of 5 tests or treatments used in rheumatology that have evidence indicating that they may be unnecessary and thus should be reevaluated by rheumatology healthcare providers and patients.Methods.Using the Delphi method, a committee of 16 rheumatologists from across Canada and an allied health professional generated a list of tests, procedures, or treatments in rheumatology that may be unnecessary, nonspecific, or insensitive. Items with high content agreement and perceived relevance advanced to a survey of Canadian Rheumatology Association (CRA) members. CRA members ranked these top items based on content agreement, effect, and item ranking. A methodology subcommittee discussed the items in light of their relevance to rheumatology, potential effect on patients, and the member survey results. Five candidate items selected were then subjected to a literature review. A group of patient collaborators with rheumatic diseases also reviewed these items.Results.Sixty-four unique items were proposed and after 3 Delphi rounds, this list was narrowed down to 13 items. In the member-wide survey, 172 rheumatologists responded (36% of those contacted). The respondent characteristics were similar to the membership at large in terms of sex and geographical distribution. Five topics (antinuclear antibodies testing, HLA-B27 testing, bone density testing, bone scans, and bisphosphonate use) with high ratings on agreement and effect were chosen for literature review.Conclusion.The list of 5 items has identified starting points to promote discussion about practices that should be questioned to assist rheumatology healthcare providers in delivering high-quality care.

To evaluate excess mortality over time, comparing rheumatoid arthritis (RA) patients with the general population.We computed all-cause mortality rates among Ontario residents age ≥15 years with RA versus without RA from 1996 to 2009. Age- and sex-standardized mortality rates were expressed as the number of deaths per 1,000 population. Excess mortality rates were calculated as the difference between death rates among RA patients and those in the general population. We estimated standardized mortality ratios (SMRs) and mortality rate ratios (MRRs) to assess relative excess mortality over time.From 1996 to 2009, SMRs in RA ranged from 13.0 (95% confidence interval [95% CI] 12.2, 13.9) to 9.2 deaths per 1,000 RA patients (95% CI 8.4, 10.0); and for those without RA from 8.7 (95% CI 8.6, 8.7) to 6.0 deaths (95% CI 5.9, 6.0) per 1,000 general population. Over the study period, the excess mortality rate among RA patients was approximately 3 excess deaths per 1,000 population. Relative reductions in standardized mortality rates occurred over time for those with and without RA (-21.4% versus -13.4%). The SMRs for RA patients in 1996-1997, 2000-2001, 2004-2005, and 2008-2009 were 1.51 (95% CI 1.43, 1.59), 1.50 (95% CI 1.43, 1.57), 1.43 (95% CI 1.37, 1.50), and 1.41 (95% CI 1.35, 1.47), respectively. We did not find a significant change in the MRR by calendar time.Mortality for RA patients has decreased over time but remains elevated compared to the general population, with 40-50% more deaths among RA patients. The relative excess mortality over time (mortality gap) remains unchanged in our sample.

Epidemiologic assessments of sufficiently large populations are required in order to obtain robust estimates of disease prevalence and incidence, particularly when exploring the influence of various factors (age, sex, calendar time). We undertook this study to describe the epidemiology of rheumatoid arthritis (RA) over the past 15 years.We used the Ontario Rheumatoid Arthritis administrative Database (ORAD), a validated population-based research database of all Ontarians with RA. The ORAD records were linked with census data to calculate crude and age and sex-standardized prevalence and incidence rates from 1996 to 2010. Vital statistics were used to estimate annual all-cause mortality during the study period.As of 2010, there were 97,499 Ontarians with RA, corresponding to a cumulative prevalence of 0.9%. Age and sex-standardized RA prevalence increased steadily over time from 473 (95% confidence interval [95% CI] 469-478) per 100,000 population (0.49%) in 1996 to 784 (95% CI 779-789) per 100,000 population (0.9%) in 2010. Age and sex-standardized incidence per 100,000 population ranged from 62 (95% CI 60-63) in 1996 to 54 (95% CI 52-55) in 2010. All-cause mortality decreased by a relative 21.4% since 1996.Over a 15-year period, we observed an increase in RA prevalence over time. This rise may be attributed to the increasing time to ascertain cases (which may have been latent in the population during earlier years of the study), increasing survival, and/or an increase in the aging background population. Incidence appears to be stable.

Background The interchangeability of Disease Activity Score 28 joints (DAS28) calculated using the erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) has been questioned (1). Objectives To compare the 28-Joint Disease Activity Score (DAS28) calculated using C-reactive protein (CRP) with that using erythrocyte sedimentation rate (DAS28-ESR) in a multi-centre, usual care, early rheumatoid arthritis (ERA) cohort. Methods The present study analyzed baseline and 12-month follow up data from the Canadian Early Arthritis Cohort. The study sample included patients with RA with symptom duration less than 12 months and complete data on DAS28-ESR and DAS28-CRP at both time points. The linear association between continuous DAS28-ESR and DAS28-CRP scores was estimated using Pearson9s correlation coefficient and differences across the range of DAS28 scores were examined with Bland-Altman Plots. Receiver operating characteristic (ROC) analysis was used to identify optimal thresholds for disease activity for DAS28-CRP scores that would best correspond with established DAS28-ESR thresholds in the total sample as well as in stratified samples by age and sex. Agreement between newly calculated DAS28-CRP and established DAS28-ESR thresholds was examined (kappa statistic). Results The study sample included 995 ERA patients. Sample baseline mean (SD) age was 53.7 (14.5) with 5.8 (2.9) months of symptom duration and 738 (74%) were female. Though continuous DAS28-CRP and DAS28-ESR scores were highly correlated (r=0.92, p Conclusions Results from this large observational study of “real-world” ERA patients showed that DAS28-CRP and DAS28-ESR scores were strongly correlated but that DAS28-CRP scores were consistently lower than DAS28-ESR scores. Differences between DAS28-CRP and DAS28-ESR were greater at lower ranges of the DAS28 and were most pronounced in women and older patients. This suggests that substituting one continuous score for the other is likely reasonable for research purposes in data analysis and that interpreting the DAS28-CRP using established DAS28-ESR thresholds may be acceptable for higher levels of disease activity, but not for lower levels, particularly not for remission. References Siemons L, Vonkeman HE, ten Klooster PM, van Riel PL, van de Laar MA. Interchangeability of 28-joint disease activity scores using the erythrocyte sedimentation rate or the C-reactive protein as inflammatory marker. Clin Rheumatol. 2014 Jun;33(6):783–9. Disclosure of Interest B. Kuriya: None declared, O. Schieir: None declared, D. Lin: None declared, J. Pope: None declared, G. Boire: None declared, B. Haraoui: None declared, C. Thorne: None declared, D. Tin: None declared, C. Hitchon: None declared, E. Keystone: None declared, V. Bykerk Grant/research support from: The CATCH study was designed and implemented by the investigators. The authors have received unrestricted grants from: Amgen Canada Inc and Pfizer Canada Inc - Founding sponsor since 2007, Hoffmann-La Roche Ltd, UCB Canada Inc, Bristol-Myers Squibb Canada, AbbVie Corporation and Janssen Inc since 2011, Medexus Inc since 2014 and Eli Lilly Canada Inc since 2015.

Preeclampsia is a serious complication of pregnancy that can compromise the health of pregnant women and neonates1. Studies have consistently shown that women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have an increased risk for preeclampsia; SLE is associated with a 2 to 6-fold increase in risk and RA is associated with a 1.4 to 2-fold increase in risk2–6. Limited data exist on the association of other autoimmune diseases, such as multiple sclerosis and inflammatory bowel disease, and preeclampsia7–8. Disease-Modifying Antirheumatic Drugs (DMARD) are a part of standard treatments for autoimmune disease, and their use during pregnancy may be necessary to avoid flares of disease that may compromise the health of the expectant mother and fetus9–10. It is possible that DMARDs may decrease the risk of preeclampsia by diminishing the maternal immune response to the placenta, which may play a role in the development of preeclampsia11. However, it is critical to account for underlying autoimmune disease when assessing the relation between DMARD use and preeclampsia given the well-reported association between various autoimmune diseases and preeclampsia2–6. Corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pregnant women with autoimmune disease9–10, 12. Corticosteroids may mitigate the systemic inflammatory response associated with preeclampsia13 and aspirin, a non-selective NSAID, modestly decreases the risk for preeclampsia14. In the study, we first described DMARD, oral corticosteroid, and NSAID use during pregnancy in a population-based cohort. We then assessed the impact of DMARDs, oral corticosteroids and NSAIDs on the risk for preeclampsia adjusting for autoimmune diseases and factors related to autoimmune disease severity.

This review examines the literature on the frequency of remission associated with different treatment approaches in early rheumatoid arthritis (ERA). Trials reporting remission outcomes were identified through searches of the CINAHL, EMBASE, and Medline (PubMed) databases from 2000 through August 2012. Additional literature was identified through hand searching. The proportion of patients achieving remission and/or radiographic non-progression was extracted from each study. Evidence was examined in the context of unified remission criteria and practical considerations for achieving and maintaining remission are discussed. The literature highlights the benefits of early treatment with disease-modifying anti-rheumatic drug (DMARD) combination therapy, combination therapy with a biologic, and tight control with a pre-specified treatment target in achieving remission in ERA. The added stringency of the 2011 remission criteria may increase the proportion of patients achieving true remission, while identifying predictors of sustained remission may also help patients achieve better radiographic and functional outcomes.

Although biologic treatments have excellent efficacy for many autoimmune diseases, safety concerns persist. Understanding the absolute and comparative risks of adverse events in patient and disease subpopulations is critical for optimal prescribing of biologics.The Safety Assessment of Biologic Therapy collaborative was federally funded to provide robust estimates of rates and relative risks of adverse events among biologics users using data from national Medicaid and Medicare plus Medicaid dual-eligible programs, Tennessee Medicaid, Kaiser Permanente, and state pharmaceutical assistance programs supplementing New Jersey and Pennsylvania Medicare programs. This report describes the organizational structure of the collaborative and the study population and methods.This retrospective cohort study (1998-2007) examined risks of seven classes of adverse events in relation to biologic treatments prescribed for seven autoimmune diseases. Propensity scores were used to control for confounding and enabled pooling of individual-level data across data systems while concealing personal health information. Cox proportional hazard modeling was used to analyze study hypotheses.The cohort was composed of 159,000 subjects with rheumatic diseases, 33,000 with psoriasis, and 46,000 with inflammatory bowel disease. This report summarizes demographic characteristics and drug exposures. Separate reports will provide outcome definitions and estimated hazard ratios for adverse events.This comprehensive research will improve understanding of the safety of these treatments. The methods described may be useful to others planning similar evaluations.

Objective To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). Methods 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results A total of 39 756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. Conclusions Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Objective The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the effi cacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure. Methods A systematic search was performed for randomised controlled trials of ERA using predefi ned criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52–56 weeks of follow-up. Results Seven trials of combination therapy with infl iximab, adalimumab, etanercept or abatacept were included. The majority of studies defi ned clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defi ned as a modifi ed total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Signifi cant heterogeneity among studies for the latter outcome was detected (p

Objective To determine whether quality of life in patients with systemic lupus erythematosus (SLE) measured by the Short Form 36 (SF-36) changes over time and which patient- and disease-related factors influence such change. Methods SLE patients who had ≥6 SF-36 evaluations during followup were identified from a database. Outcomes were slopes of scores of the 8 SF-36 domains as well as the physical and mental component scores. Based on the direction of the slope, patients were designated as unchanged, improved, or worsened. Linear regression models were used to test the contribution of risk factors to slopes. Nonparametric tests were used to evaluate risk factors between patterns of clinical change. Results A total of 146 patients had ≥6 SF-36 evaluations in 1,047 visits over a mean ± SD period of 8.2 ± 1.1 years. During the interval, the majority of patients showed no change in the SF-36 domains and only a small minority demonstrated improvement. Physical and mental component scores were unchanged in 84.3% and 87.7% of patients whereas 4.1% and 7.5% improved, respectively. According to slopes of the domains and summary scores, only physical functioning demonstrated a significant decrease over time. There were no lupus disease features associated with decline in physical functioning except for the presence of fibromyalgia. Conclusion The SF-36 in SLE patients with established disease changed little over an 8-year period. Changes in the SF-36 were not affected by disease activity, steroids, or damage accumulation during the interval, but were affected by the presence of fibromyalgia.

Background Disease progression in longitudinal studies of rheumatoid arthritis (RA) is usually assessed by examining a measure of disease over fixed time intervals; results can be presented as the mean of the whole group or, for subgroups sharing common underlying characteristics. These approaches do not addresses individual within-patient changes over time. In contrast, a multi-state model classifies each patient into one of several pre-defined disease states at patient visit and examines moves between disease states over time. Objectives The objectives were: (1) to provide a descriptive analysis of patients9 disease states defined by the DAS-28 throughout the first three years of treatment; (2) to determine the time spent in each disease state; and (3) to estimate the probabilities of changing between disease states. Methods From a large ongoing prospective study of RA in Ontario, Canada (OBRI), patients who met the following inclusion criteria were selected: 1) incident RA, 2) active disease (≥1 swollen or tender joint) and 3) at least 2 follow-up visits to their rheumatologist. The DAS-28 disease score was collected at each visit and patients were classified in one of four DAS-28 categories, from remission to high disease activity. A multi-state (in this case 4-state) Markov model was fitted to describe patient progression through disease states over time. Traditional assumptions of Markov models are equal intervals between visits, which do not reflect the clinical reality of irregular visits. We fitted a novel Markov model to account for the irregular time intervals considering time as a continuous variable allowing us to examine real-world disease course over time. Results There were 3014 visits in 586 patients over the 3-year follow-up window (see figure). At baseline, 43% of patients were in DAS-28 high disease activity, but patients, moved out of this health state rapidly on average 0.17 years, 95% CI (0.19, 0.23). At baseline 9% of patients were in DAS-28 remission, increasing to 30% at 6 months and 45% at 1 year. Once a patient achieved remission, the mean duration before moving to another disease state was 0.81 years, 95% CI (0.67, 0.97). By 1.5 years after initiation of treatment, patients in each disease state remained relatively constant indicating no net movement between health states. Conclusions We identified that individual patients transition between disease states rapidly in the first 3 years of treatment when observed in usual care. Our analysis indicates the critical first year of treatment before a steady disease state with no net movement will be reached. Major changes in the first year of treatment especially in the first 6 months could be a result of treat-to target strategy but do not occur as quickly as specified by treat-to-target guidelines indicating possible gaps in care. Future research will adjust for covariates including drug history and demographic factors while also examining between physician differences. Disclosure of Interest None declared

Background Patients with rheumatoid arthritis (RA) have an increased mortality compared with the general population. 1 Established risk factors for premature mortality include active inflammation/disease activity, comorbidity and extra-articular disease manifestations. Thus, early and greater exposure to disease-modifying anti-rheumatic drugs (DMARDs) may mitigate these risk factors and improve survival in RA. Objectives Our aim was to evaluate the associations between RA drug exposures and survival in seniors with incident RA. Methods This retrospective cohort study investigated all incident cases of RA diagnosed from 2000 to 2013. We studied a subset of patients within the Ontario RA Database (ORAD) - a validated population-based cohort of all Ontarians with RA - who were aged 66 years and older who have comprehensive public drug insurance. We used Cox proportional hazards regression to investigate mortality, defined as death from any cause, exploring time-dependent cumulative drug exposures during the entire duration of follow-up, while adjusting for baseline age, sex, urban vs. rural residence, socioeconomic status, pre-existing comorbidities (e.g. hypertension, COPD, diabetes, coronary artery disease, cancer), past drug exposures, time-dependent number of physician visits, and extra-articular manifestations of RA (as proxies for RA severity). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Results Among 25,416 senior RA patients, 67.8% were female, the mean (SD) age was 75.2 (6.5) years, and 85.4% lived in urban areas. During median and maximum follow-up times of 4.4 and 13.2 years, respectively, 7,956 patients died (31.3%) for a mortality rate of 6.2 per 100 person-years. In multivariable analyses, we observed no association between greater cumulative exposure to methotrexate, other DMARDs, or anti-TNF agents and survival. Greater exposure to corticosteroids was associated with greater risk of mortality [HR 1.15 (95% CI 1.14-1.17)], as were greater baseline comorbidity [Charlson HR 1.36 (95% CI 1.34-1.38)] and extra articular disease [HR 1.53 (95% CI 1.47, 1.61)]. Females and residents living in urban areas had lower mortality risk [HR 0.78 (95% CI 0.75-0.82) and HR 0.92 (95% CI 0.86-0.98), respectively]. Conclusions Though we could not demonstrate an association between exposure to DMARDs and over-all survival in seniors with RA, cause-specific mortality warrants further investigation. Greater exposure to corticosteroids, comorbidity and extra articular RA was associated with pre-mature mortality in our sample. References Widdifield et al, Trends in Excess Mortality among Patients with Rheumatoid Arthritis in Ontario, Canada. Arthritis Care & Research 2015 [in press]. Disclosure of Interest None declared

Background Comorbidity is an important prognosis and health outcome in rheumatic diseases and an important confounder or effect modifier in epidemiologic studies. Researchers face challenges regarding the optimal way to accurately measure comorbidity and there is a lack of information on the reporting and level of agreement of comorbidities obtained from different data sources. Objectives We investigated the prevalence of reporting and level of agreement of three specific comorbidities independently ascertained from rheumatologists, patients and health administrative data. Methods We studied patients enrolled in the Ontario Best Practices Research Initiative RA registry, which embeds clinical data collection into routine practice. Patients and rheumatologists independently report comorbidities using standardized questionnaires. To identify comorbidities ascertained from health administrative data, we performed deterministic linkage using coded health insurance numbers to link with the Ontario Cancer Registry, and the Ontario Diabetes Database and the Ontario Hypertension Database - the latter two of which are derived using validated administrative data case definitions. For these initial comorbidities of interest, we report the prevalence of each condition based on the method of ascertainment and the level agreement between data sources. Sensitivity, specificity and predictive values were calculated by alternating the reference standard (rheumatologist or patient) to assess the accuracy of the administrative data definitions. Results 1787 patients (97%) were successfully linked. The prevalence of cancer, diabetes and hypertension reported by rheumatologists were lower than those reported by both patients and administrative data (table). Patients reported more cancers than rheumatologists and administrative data, which is further illustrated in the lower sensitivity of administrative data in detecting cancers. There was substantial agreement between each of the three comorbidities ascertained from each data source (kappas ranging from 0.53-0.79). The accuracy of administrative data for comorbidity ascertainment was modest to excellent, regardless of the reference standard definition. Conclusions For the initial comorbidities we studied, there was substantial correlation between rheumatologists, patients and health administrative data, but the prevalence varied by data source. Patients reported more previous cancers, which may reflect that basal and squamous cell carcinomas are not registered in the Cancer Registry or cancers pre-dating capture in the Registry. Thus, linkages between clinical registries (which capture patient- and physician-reported outcomes) and administrative data may overcome some of the limitations of imperfect ascertainment from using one data source alone. Acknowledgements Disclosure of Interest None declared

Background Cardiovascular disease (CVD) is a major comorbidity and the leading cause of death among patients with rheumatoid arthritis (RA) 1 . Objectives To compare the demographics, patterns of medication use, and disease activity in RA patients with and without CVD at cohort entry and 12 months of follow-up. Methods Physician and patient-reported data were collected from the Ontario Best Practices Research Initiative Rheumatoid Arthritis Registry (OBRI- RA), a clinical registry of RA patients followed in routine care. CVD was defined as the presence of coronary artery disease (CAD), congestive heart failure (CHF), hypertension (HTN), arrhythmia, stroke, transient ischemic attack (TIA), and/or other heart disorders upon entering the registry. Patient demographics, clinical characteristics, socioeconomic status and treatment regimens were compared between CVD and non-CVD patients at cohort entry using Chi- square and t-tests. Mean disease activity and functional status scores at cohort entry and 12 months of follow-up were estimated by generalized linear regression, adjusting for confounders, including age, sex, smoking, socioeconomic factors, disease activity at cohort entry (for 12-month follow-up analyses only), and RA duration. Results Among 2226 RA patients, 360 (16.2%) had CVD at cohort entry. Among which, 101 (28.1%) had CAD, 51 (14.2%) had arrhythmia, 12 (3.3%) had CHF, 28 (7.8%) had CVA, 8 (2.2%) had PE, and 160 (44.4%) had other/unspecified CVD. Patients with CVD were older (66.7±10.1 vs. 53.6±12.9yrs, p Conclusions At cohort entry, RA patients with CVD have worse disease activity (RADAI) and functional status (HAQ-DI). At 12 months of follow-up, disease activity (DAS28) remained worse among CVD patients. The higher ESR found in CVD patients may suggest heightened systemic inflammation 1 . The lower use of NSAIDS may be due to their known CVD risks, but the higher utilization of glucocorticoids may require further investigation. References Choy E, Ganeshalingam K, Semb AG, et al. Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology (2014) 53 (12):2143-2154. Acknowledgements Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology. We also thank the OBRI investigators for ongoing data collection for the OBRI registry. Disclosure of Interest None declared

The principal role of the mammalian coronary microcirculation is to provide oxygen to the working heart. Terminal arteries and arterioles regulate coronary nutritive blood flow and the capillary net provides the structural basis for oxygen transport by the process of diffusion. Most of our previous research has focussed on the predominant component of the microvascular bed, namely, coronary capillaries. In this connection, the amount of tissue supplied by individual coronary capillaries and the variability of capillary spacing have been found to constitute two of the principal oxygen determinants (Turek et al., 1991). Both may be derived from measuring the size of individual capillary domains, defined as tissue cross-sectional areas closer to a given capillary than to any other. As the distribution of these domain areas is log-normal, the standard deviation of this distribution (SDlog) best serves as a heterogeneity index of capillary spacing. Our established histochemical method (Batra et al., 1989) has previously been used to provide color distinction within capillary regions: proximal capillary portions i.e., close to feeding arterioles having larger capillary domains stain blue, while those within distal capillary regions and with smaller domain areas stain red. Despite widespread acceptance of our technique, some reservation has nevertheless been put forward as to the validity of this approach in distinguishing unambiguously separate capillary regions.

Background Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD). Methods Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months. Results We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075). Conclusion Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.