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Objective To investigate the incidence of and factors associated with SARS-CoV-2 testing and infection in immune mediated inflammatory diseases (IMIDs) versus matched non-IMIDs comparators from the general population. Methods We conducted a population-based, matched cohort study among adult residents from Ontario, Canada, from January to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica and vasculitis. Each patient was matched with five patients without IMIDs based on socio-demographic factors. We estimated the incidence of SARS-CoV-2 testing and infection in IMIDs and non-IMIDs patients. Multivariable logistic regressions assessed odds of SARS-CoV-2 infection. Results We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least one SARS-CoV-2 test, versus patients without IMIDs (27.4% vs. 22.7%), but the proportion testing positive for SARS-CoV-2 was identical (0.9% in both groups). Overall, IMIDs patients had 20% higher odds of being tested for SARS-CoV-2 (odds ratio (OR) 1.20, 95% CI 1.19, 1.21). The odds of SARS-CoV-2 infection varied across IMIDs groups but was not significantly elevated for most IMID groups compared with non-IMIDs. The odds of SARS-CoV-2 infection was lower in IBD and MS and marginally higher in RA and iritis. Conclusions Patients across all IMIDs were more likely to be tested for SARS-CoV-2 versus those without IMIDs. The risk of SARS-CoV-2 infection varied across disease sub-groups.

Aims To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). Methods and results The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014–19. The treatment goal for BP was Conclusion We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

Objective Patients have identified pain, fatigue and independence as the most important domains that need to be improved to define remission in rheumatoid arthritis (RA). This study identified and validated instruments for these domains and evaluated their added value to the ACR/EULAR Boolean remission definition. Methods Patients with a 28-joint Disease Activity Score (DAS28) ≤3.2 or in self-perceived remission (declaring their disease activity ‘as good as gone’) from the Netherlands, Portugal, Australia, and Canada, were assessed at 0, 3 and 6 months for patient-reported outcomes and the WHO-ILAR RA core set. Instrument validity was evaluated cross-sectionally, longitudinally and for the ability to predict future good outcome in terms of physical functioning. Logistic regression quantified the added value to Boolean remission. Results Of 246 patients, 152 were also assessed at 3, and 142 at 6 months. Most instruments demonstrated construct validity and discriminative capacity. Pain and fatigue were best captured by a simple numerical rating scale (NRS). Measurement of independence proved more complex, but a newly developed independence NRS was preferred. NRS for pain, fatigue and independence, in addition to or instead of patient global assessment did not add enough information to justify modification of the current Boolean definition of remission in RA. Conclusion Key elements of the patient perspective on remission in RA can be captured by NRS pain, fatigue, and independence. Although this study did not find conclusive evidence to improve the current definition of remission in RA, the information from these instruments adds value to the physician's assessment of remission and further bridges the gap between physician and patient.

Objective\ud To determine how best to incorporate the patient perspective into rheumatoid arthritis remission criteria.\ud \ud Methods\ud At OMERACT 2020, several studies, including a longitudinal multi-centre study testing the validity of adding patient-valued domains to the ACR/EULAR criteria, were presented and discussed by the virtual Special Interest Group.\ud \ud Results\ud Overall consensus was that there is insufficient evidence to change the remission criteria at this point. Future work should focus on measurement of the new domain of independence, clarifying the value of the patient global assessment, and optimizing the input of domains that patients value in the criteria.\ud \ud Conclusion\ud Incorporating the patient perspective into remission criteria should be further explored.

Objective Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods A cross‐sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex‐stratified logistic regression identified baseline variables associated with MetS. Results The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high‐density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

Objective Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with mental illness. The risk of serious mental illness, including deliberate self-harm (DSH), in these conditions is not well known. We aimed to determine if RA or AS independently increases the risk for DSH. Methods We conducted retrospective, population-based cohort studies using administrative health data for the province of Ontario, Canada between April 1, 2002 and March 31, 2014. Individuals with incident RA (N = 53,240) or AS (N = 13,964) were separately matched 1:4 by age, sex, and year with comparators without RA or AS. The outcome was a first DSH attempt identified using emergency department data. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for risk of DSH in RA and AS versus comparators, adjusting for demographic, clinical and health service utilization variables. Results Subjects with AS were significantly more likely to self-harm (crude incidence rate [IR] of 0.68/1,000 person years [PY] versus 0.32/1,000 PY in comparators), with an adjusted HR of 1.59 (95% CI 1.15 to 2.21). DSH was increased for RA subjects (IR 0.35/1,000 PY) versus comparators (IR 0.24/1,000 PY) only before (HR 1.43, 95% CI 1.16 to 1.74), but not after covariate adjustment (HR 1.07, 95% CI 0.86 to 1.33). Conclusions AS carries an increased risk for DSH but no such risk was observed in RA. Further evaluation of at-risk AS subjects is needed, including the longitudinal effects of disease and arthritis therapies on self-harm behaviour. This will inform whether specific risk-reduction strategies for DSH in inflammatory arthritis are needed.

Background Rheumatoid arthritis increases the risk of cardiovascular disease (CVD). Less is known about the direct influence of CVD and CVD risk factors (RF) on RA outcomes, but higher comorbidity burden has been suggested to adversely affect RA treatment response1-2. Objectives We tested our hypothesis that CVD risk factors (RFs) alone, in the absence of CVD, are associated with higher disease activity and disability in RA. Methods The Ontario Best Practices Research Initiative (OBRI) is a clinical registry of RA patients followed in routine care. RA subjects with complete data to calculate disease activity according to the Disease Activity Score-28 (DAS28), Clinical Disease Activity Index (CDAI), 28 swollen joint count (SJC28) and functional status (Health Assessment Questionnaire Disability Index [HAQ-DI]) at cohort entry were selected. Patients were divided into mutually exclusive groups by baseline CVD status as: (1) no CVD/no CVD RFs; (2) CVD including coronary artery disease, myocardial infarction, cerebral vascular accidents, and peripheral arterial disease; (3) no CVD but CVD RFs including hypertension (HTN), dyslipidemia (DLD), diabetes (DM), or smoking. We performed separate linear regression analyses for each outcome, adjusted for baseline clinical and demographic variables, to determine the independent effect of CVD status on disease outcomes at baseline and one year follow-up. Results Of 2033 patients examined, 49.5% had no CVD, 5.4% had CVD and 45.1% had CVD RFs alone. The most common RF was HTN (33%) followed by DLD (19.7%), current smoking (17%), and DM (8.1%). At cohort entry, having a CVD RF was associated with significantly higher DAS28 (β 0.13, 95%CI 0.002-0.26, p 0.04) and HAQ-DI (β 0.16, 95%CI 0.10-0.23, p Conclusion Even in the absence of CVD, traditional CVD RF are associated with greater RA disease severity and disability both at baseline and one year. Self-perceived impact of comorbidity (patient global assessment of health) may be driving this relationship. Moreover, patients with CVD RF maybe more treatment-resistant, suggesting that co-management of CVD RF in RA patients may be beneficial on both fronts. References [1] Avina-Zubieta, J. A., Thomas, J., Sadatsafavi, M., Lehman, A. J. & Lacaille, D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann. Rheum. Dis. 71, 1524–1529 (2012). [2] Crepaldi, G. et al. Cardiovascular Comorbidities Relate More than Others with Disease Activity in Rheumatoid Arthritis. PLoS One11, (2016). Acknowledgement OBRI investigators Disclosure of Interests Kangping Cui: None declared, Mohammad Movahedi Employee of: ONTARIO BEST PRACTICE RESEARCH INITIATIVE (OBRI), Claire Bombardier Grant/research support from: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Hospira, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, Speakers bureau: Roche, Bindee Kuriya Consultant for: Advisory Board Member: Abbvie, Sanofi Genzyme, Eli Lilly, Pfizer Canada, Roche

Background Individuals with rheumatoid arthritis (RA) are at risk of developing cardiovascular disease (CVD), but patient perceptions of CVD are not routinely assessed. We performed a systematic literature review to evaluate awareness of the association between RA and CVD, and perceived risk of CVD among individuals with RA. Methods Three electronic databases (MEDLINE, EMBASE, and PubMed) were searched for English language articles between the years of 1990–2018. Search terms pertained to RA, CVD, knowledge, awareness, or perceptions of CVD risk. Abstracts were screened for inclusion/exclusion by two independent reviewers. Results A total of 33 abstracts were screened and 6 underwent full review. The overall sample size was 478 subjects and included patients with established RA who were predominantly female with a mean age range of 53 to 64 years. RA disease characteristics relevant to CVD were not uniformly reported, including the use of DMARDs, corticosteroids, or NSAIDs. A high proportion of subjects (range 73 to 97%) were unaware of an increased risk of developing CVD in relation to their RA, and this frequently occurred in those with a greater number of traditional CVD risk factors. Misperceptions about CVD were common, and the majority of subjects misestimated their actual CVD risk. Conclusion Individuals with RA at highest risk for CVD report low awareness and perceived risk of this comorbidity. This represents a knowledge gap in need of intervention but must be tailored to patients’ needs. An understanding of the system- and individual-level barriers preventing CVD awareness is needed. Only then will approaches to improve CVD screening and management in RA be successful. Electronic supplementary material The online version of this article (10.1186/s13075-019-1817-y) contains supplementary material, which is available to authorized users.

Aims: Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD), but the influence of CVD risk factors on RA outcomes is limited. We examined if CVD risk factors alone are associated with RA disease activity and disability. Methods: We performed a cross-sectional analysis of participants in the Ontario Best Practices Research Initiative, RA registry. Patients were categorized into mutually exclusive CVD categories: (1) No established CVD and no CVD risk factors; (2) CVD risk factors only including ⩾1 of hypertension, dyslipidemia, diabetes, or smoking; or (3) history of established CVD event. Multivariable regression analyses examined the effect of CVD status on Disease Activity Score 28 (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI) scores at baseline. Results: Of 2033 patients, 50% had at least 1 CVD risk factor, even in the absence of established CVD. The presence of ⩾1 CVD risk factor was independently associated with higher CDAI [β coefficient 1.59, 95% confidence interval (CI) 0.29–2.90, p = 0.02], DAS28-ESR (β coefficient 0.20, 95% CI 0.06–0.34, p = 0.01) and HAQ-DI scores (β coefficient 0.15, 95% CI 0.08–0.22, p 1 CVD risk factor was associated with higher disease activity and disability, compared with having one or no CVD risk factors. Conclusion: CVD risk factors alone, or in combination, are associated with higher disease activity and disability in RA. This emphasizes the importance of risk factor recognition and management, not only to prevent CVD, but also to improve potential RA outcomes.

Objective.We evaluated the associations between time-varying methotrexate (MTX) use and risk of cardiovascular events (CVE) in patients with rheumatoid arthritis (RA).Methods.We studied an inception cohort of 23,994 patients with RA diagnosed after their 65th birthday. Multivariable Cox regression models were fit to evaluate the associations between time-varying MTX use, controlling for other risk factors, and time to CVE. Alternative models assessed the cumulative duration of MTX use over the (1) first year, (2) previous year (recent use), and (3) entire duration of followup. We also assessed whether the strength of the association varied over time.Results.Over 115,453 patient-years (PY), 3294 (13.7%) patients experienced a CVE (28.5 events per 1000 PY; 95% CI 27.6–29.5). In the multivariable analyses, the model assessing time-varying continuous use in the most recent year yielded the best fit. Increasing recent MTX use was associated with lower CVE risks (HR 0.79 for continuous use vs no use in past 12 months, 95% CI 0.70–0.88; p < 0.0001). Greater MTX use in the first year after cohort entry was also protective (HR 0.84, 95% CI 0.72–0.96; p = 0.0048), but this effect decreased with increasing followup. In contrast, longer MTX use during the entire followup was not clearly associated with CVE risk (HR 0.98, 95% CI 0.95–1.01; p = 0.1441).Conclusion.We observed about a 20% decrease in CVE associated with recent continuous MTX use. Greater MTX use in the first year of cohort entry also appeared to be important in the association between MTX and CVE risk.

Background Inflammatory arthritis is associated with the development of mental health disorders. However, there is limited data on the risk of serious mental health outcomes following a rheumatoid arthritis (RA) or ankylosing spondylitis (AS) diagnosis. Objectives To estimate the risk of deliberate self-harm in patients with ankylosing spondylitis or rheumatoid arthritis compared with the general population. Methods We evaluated population-based cohorts of RA (n=53,240) and AS (n=13,964), each matched 1:4 by age, sex, and calendar year (at diagnosis) with non-IA comparator cohorts in Ontario, Canada. Individuals with a history of mental illness or prior episode of deliberate self-harm were excluded. The outcome was a first emergency room presentation for deliberate self-harm, subsequent to RA or AS diagnosis, between April 1, 2002 and March 31, 2016. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for RA and AS, separately, versus the comparator groups, adjusting for demographic, clinical and health service utilisation variables. Results Individuals with AS were more likely to deliberately self-harm (incidence rate [IR] of 6.79/10,000 person years [PY] compared to 3.19/10,000 PY in comparators, with an adjusted HR 1.82 (95% CI: 1.26 to 2.62). Deliberate self-harm was also increased for individuals with RA (IR 3.51/10,000 PY) compared to comparators (IR 2.45/10,000 PY) only before (HR 1.43, 95% CI: 1.16 to 1.75), but not after covariate adjustment (HR 1.09, 95% CI: 0.88 to 1.36). The most frequent method of self-harm was poisoning (64% of attempts in AS, 81% in RA) or self-mutilation (36% in AS, 18% in RA). Conclusions There is a significantly increased rate of self-harm attempt in inflammatory arthritis and the risk is particularly elevated following a diagnosis of AS. These findings highlight the need for routine evaluation of self-harm behaviour as part of the management of chronic inflammatory arthritis. Understanding the mechanisms contributing to deliberate self-harm attempts will help tailor preventive strategies to reduce morbidity associated with this serious mental health outcome. Acknowledgements This work was funded by the Division of Rheumatology Pfizer Research Chair, University of Toronto Disclosure of Interest None declared

Objective.We sought to determine if initial high disease activity or changes in disease activity contribute to persistent depression in early rheumatoid arthritis (ERA). We also determined if disease activity and depression is modified by sex.Methods.Depression was ascertained by self-report among patients enrolled in the Ontario Best Practices Research Initiative. The association between baseline disease activity, measured by the Clinical Disease Activity Index (CDAI), and persistent depression was evaluated with multivariate regression models, and effect modification by sex was tested. A general estimating equation assessed the association between change in CDAI over time and risk of depression.Results.The sample of 469 ERA subjects was predominantly female (73%). At baseline, the prevalence of depression was 26%, and 23% reported persistent depression. After adjusting for potential confounders, higher baseline CDAI was associated with both baseline and persistent depression (OR 1.03, 95% CI 1.01–1.05). Female sex was an effect modifier of this relationship (OR 1.04, 95% CI 1.01–1.06). Maintaining a moderate or high CDAI score over 2 years also increased the risk of future depression.Conclusion.Depression in ERA is common and initial high disease activity is associated with the probability of depression and its persistence. This risk seems particularly modified in women with active disease and represents an area for targeted focus and screening. Future studies in ERA are needed to determine if intervening during the “window of opportunity” to control disease activity has the potential to mitigate the development and maintenance of adverse mental health outcomes, including depression.

This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA

Objective To evaluate excess mortality over time, comparing rheumatoid arthritis (RA) patients with the general population. Methods 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. Results 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. Conclusion 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.

Objective.The Outcome Measures in Rheumatology (OMERACT) working group on the patients’ perspective on remission in rheumatoid arthritis (RA) has been working on this topic since 2010. At OMERACT 2016, progress and preliminary data on validity of measurement instruments for pain, fatigue, and independence in remission in RA were presented, and future directions were explored.Methods.A special interest group was organized, in which the current data on the patients’ perspective on remission were presented. The ongoing study that aimed to validate measurement instruments for pain, fatigue, and independence in a state of low disease activity or remission was presented, and preliminary data on construct validity and discriminative capacity were evaluated cross-sectionally.Results.At OMERACT 2016, the progress of the working group and preliminary data from 142 of the anticipated 300 patients were presented. Selected instruments significantly correlated with the Disease Activity Score in 28 joints (construct validity) and all instruments except 1 discriminated between patients in and patients not in remission. The subsequent discussion mainly focused around 3 points: (1) the formulation of patient perceived remission, (2) the duration of remission, and (3) the measurement of the domain independence. An informal vote indicated a slight preference for working toward modifying the current remission criteria by adding patient-reported outcomes (PRO), or by substituting the patient’s global assessment with 1 or more PRO.Conclusion.More evidence on measuring patients’ perspective on remission in RA is needed before an informed decision can be made regarding development or modification of remission definitions.

Objective.To evaluate the prevalence and predictive factors of sustained remission in an early rheumatoid arthritis (ERA) population. Predictive factors of sustained remission in ERA are unknown. We hypothesized that a short time to remission is an important predictor of sustained clinical remission.Methods.Patients in the Canadian Early Arthritis Cohort were included. Remission was defined by Boolean-based American College of Rheumatology/European League Against Rheumatism clinical trial and clinical practice definitions and Simplified Disease Activity Index (SDAI). Logistic regression analysis identified predictors of sustained remission and influence of time to remission.Results.Of 1840 patients, 633 (34%) achieved clinical trial remission, 759 (41%) clinical practice remission, and 727 (39%) SDAI remission. Over half of those meeting remission criteria achieved sustained remission based on clinical trial (55%), clinical practice (60%), and/or SDAI (58%). Corticosteroid use and lack of initial disease-modifying antirheumatic drug (DMARD) were associated with decreased probability of sustained remission, while initial combination DMARD increased this probability. Female sex, greater pain, and longer time to first remission made sustained remission less likely.Conclusion.Female sex, greater pain, and lack of initial DMARD therapy reduced the probability of sustained remission. A shorter time to remission is related to sustainability and supports striving for early remission.

Objective 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. Methods 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. Results 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. Conclusion 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.

Objective To determine the rate of induced abortions in women with rheumatoid arthritis (RA) exposed to methotrexate (MTX) compared with women with RA unexposed to this medication. Methods We performed a nested case–control study using administrative databases from Quebec. All women with RA ages 15–45 years were identified and cases were defined as women having an induced abortion. Each case was matched to ≥1 controls for age, calendar time, and cohort entry. Exposure was defined as having filled ≥1 prescriptions of MTX ≤16 weeks prior to the index date. Results We identified 112 cases of induced abortions in women with RA and 5,855 RA controls. Exposure to MTX occurred in 10.7% of cases and 21.7% of controls. Women exposed to MTX had a lower rate of induced abortions compared with unexposed women (rate ratio [RR] 0.47 [95% confidence interval (95% CI) 0.25–0.89]). In the multivariate analysis, there was a trend toward an increased rate of induced abortions among women exposed to anti–tumor necrosis factor (anti-TNF) agents (RR 2.07 [95% CI 0.81–5.27]). Conclusion Women with RA exposed to MTX have a lower rate of induced abortions than unexposed women. Women with RA exposed to anti-TNF agents may have an increased rate of induced abortions compared to unexposed women.

Objective.To describe the frequency of remission in an early rheumatoid arthritis (ERA) cohort.Methods.The frequency of remission was evaluated, based on 8 definitions including the Boolean-based American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria.Results.Of 369 patients, remission at 12 months ranged from 18% according to the ACR/EULAR clinical trial criteria to 40% according to the 28-joint Disease Activity Score (DAS28) < 2.6. Higher tender joint count, swollen joint count, and physician global scores were seen for DAS28-based definitions, and patient global assessment (PtGA) scores were almost 5-fold higher for DAS28 remission.Conclusion.Remission is achievable in ERA but its frequency differs according to the remission definition applied. Adoption of the new ACR/EULAR definition will limit the number classified as in remission, especially if the PtGA criteria are rated high for reasons other than inflammatory arthritis.

Objective.We aimed to systematically review rheumatoid arthritis (RA) disease severity indices for use in administrative healthcare databases. We also provide an overview of alternative methods to control for RA disease severity in administrative database research.Methods.We conducted a systematic review of studies that developed/validated an index for RA disease severity using variables in administrative databases, and compared the convergent validity/reliability of the index with a standard measure of RA severity.Results.After reviewing 539 articles, 2 studies were included. The claims-based index for RA severity (CIRAS) was developed in one study. Components of the CIRAS included tests for inflammatory markers, number of chemistry panels/platelet counts ordered, rheumatoid factor test, number of rehabilitation and rheumatology visits, and Felty’s syndrome. The CIRAS correlated moderately well with a previously validated RA medical records-based index of severity. The second study assessed whether current and lifetime treatment with disease-modifying antirheumatic drugs and/or biologics accurately predicted RA severity, as measured by the patient-reported Patient Activity Scale (PAS). Treatment variables did not fully distinguish patients in the highest and lowest quartiles of PAS scores (67.2% correctly classified).Conclusion.Two claims-based indices of RA severity were identified but have some limitations for routine use. A concerted effort from experts in the field is needed to define, develop, and validate a widely applicable measure of RA disease severity for administrative database research.

Objective To characterize therapies prescribed during pregnancy to women with rheumatoid arthritis (RA). Methods We conducted a cohort study of women with RA with pregnancies using health care utilization data from 2002–2008. We examined the distribution of RA drugs by therapeutic classes, including nonsteroidal antiinflammatory drugs (NSAIDs)/coxibs, glucocorticoids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs, during 90-day pregnancy trimesters and the 180 days prior to pregnancy. Drugs were characterized according to the Food and Drug Administration risk classification system. Differences in exposure by period were determined by chi-square tests. Results A total of 393 pregnancies were identified among 34,169 women with RA. Seventy-two percent of pregnancies ended in a delivery. Approximately 24% of women with RA received a DMARD during preconception. At any point during pregnancy, 23% of women with deliveries were dispensed ≥1 DMARD and the proportion of use declined from the first to the third trimester (P = 0.03). Similar to DMARD therapy, use of NSAIDs/coxibs and exposure to category D/X medications were significantly lower compared to prepregnancy use (P < 0.05). In contrast, more women were prescribed glucocorticoids during pregnancy than before pregnancy. Use of biologics occurred in 12.5% of pregnancies. Compared to women with deliveries, women who experienced abortions were more frequently exposed to NSAIDs/coxibs (P < 0.05). Dispensing of category D/X medications was also higher in women with spontaneous abortions and primarily involved methotrexate (P < 0.05). Conclusion Approximately 24% of women with RA received a DMARD in the 180 days before conception, and the proportion dropped during pregnancy. Glucocorticoid use remained high throughout pregnancy. Our results suggest that continued efforts directed at counseling women and their physicians about the potential risks/benefits of RA therapies during pregnancy are warranted.

Objective. To systematically review the differential diagnosis and minimal clinical investigation used prior to making a diagnosis of undifferentiated peripheral inflammatory arthritis (UPIA). Methods. A systematic literature search was performed for articles published between January 1950 and December 2008 in Medline and Embase, and for abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR). Studies including defined cohorts of patients with UPIA were retrieved according to predefined inclusion/exclusion criteria. Selected studies were systematically reviewed and relevant data extracted. Baseline characteristics were also recorded to obtain a clinical picture of patients classified as UPIA. Results. Seventy-four articles were included. Of those, 52 reported baseline characteristics. Tremendous variation existed among studies, reflecting the different inclusion/exclusion criteria used. Rheumatoid arthritis, spondyloarthropathies, osteoarthritis, crystal arthritis, connective tissue diseases, and infections were the most common diagnoses of exclusion for UPIA and made up the other subsets of patients in cohorts with mixed populations. The baseline investigation undertaken prior to diagnosis of UPIA was reported in 7 articles. History, physical examination, tender and swollen joint count, rheumatoid factor, HLA-B27, erythrocyte sedimentation rate, C-reactive protein, and radiographs of hands and feet were the only items mentioned in at least 50% of the reports. Conclusion. Studies of UPIA are heterogeneous. Few studies reported on the minimal clinical investigation necessary to arrive at a diagnosis of UPIA. Differential diagnosis usually consisted of the most common rheumatologic conditions but could be vast.

Objective. To review the diagnostic and prognostic value of history/physical examination among patients with undifferentiated peripheral inflammatory arthritis (UPIA). Methods. We conducted a systematic review evaluating the association between history/physical examination features and a diagnostic or prognostic outcome. Results. Nineteen publications were included. Advanced age, female sex, and morning stiffness were predictive of a diagnosis of rheumatoid arthritis (RA) from UPIA. A higher number of tender and swollen joints, small/large joint involvement in the upper/lower extremities, and symmetrical involvement were associated with progression to RA. Similar features were associated with persistent disease and erosions, while disability at baseline and extraarticular features were predictive of future disability. Conclusion. History/physical examination features are heterogeneously reported. Several features predict progression from UPIA to RA or a poor prognosis. Continued measurements in the UPIA population are needed to determine if these features are valid and reliable predictors of outcomes, especially as new definitions for RA and disease states emerge.

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

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.

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

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.