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ObjectiveWe evaluated the epidemiology, manifestations, serology, comorbidities, and survival among patients with systemic sclerosis (SSc) with and without sarcoidosis.MethodsWe conducted a retrospective cohort study comparing patients with SSc with and without sarcoidosis. All patients fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc. Sarcoidosis was based on physician diagnosis and/or confirmatory biopsy. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier curves.ResultsWe included 1977 patients (1971 with SSc, 6 with SSc–sarcoidosis) with a SSc–sarcoidosis prevalence of 0.30%. Sarcoidosis frequently preceded SSc (66.66%). The most frequent sarcoidosis manifestations were pulmonary (66.66%), lymphadenopathy (66.66%), arthritis (50%), cutaneous (33.33%), and hepatic (16.66%). Patients with SSc and SSc–sarcoidosis had female to male sex ratios of 4.5:1 vs 5:1 and median ages of SSc onset of 48.3 vs 43.8 years, respectively. Interstitial lung disease (35% vs 66.66%) and pulmonary hypertension (24.91% vs 50%) tended to occur more frequently whereas abnormal nailfold capillaries (34.7% vs 16.66%) and digital ulcers (33.33% vs 16.66%) tended to occur less frequently among patients with SSc–sarcoidosis, but the differences were not significant. There was an increased frequency of stroke among the patients with SSc–sarcoidosis (relative risk 8.59, 95% CI 1.02-72.00). The median survival times were 23.4 years for SSc–sarcoidosis and 18.6 years for SSc, with no differences in survival curves (log-rank test,P =0.55).ConclusionSarcoidosis in SSc is rare but appears to occur more frequently than in the general population. It is associated with pulmonary, lymph node, cutaneous, joint, and hepatic involvement. Stroke occurs more frequently in patients with SSc–sarcoidosis but with no differences in survival.

Patients with inflammatory arthritis (IA) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet management of dyslipidemia is infrequently prioritized. We applied Canadian dyslipidemia guidelines to determine how many patients with IA would be eligible for primary prevention with statins.We conducted a cross-sectional study of patients with IA in a cardio-rheumatology clinic, with no known CVD and without statin therapy at cohort entry. We stratified patients by Framingham Risk Score (FRS) and summarized the proportion meeting guideline statin-indicated criteria. Multivariable logistic regression analyses determined the association of variables with statin indication after adjustment for age, sex, traditional ASCVD risk factors, and arthritis characteristics.Among 302 patients, most had rheumatoid arthritis (59%). Mean age was 58 years, and 71% were female. Overall, 50% of the cohort was eligible for statin therapy. The majority was low FRS risk category (68%), and the most frequent qualifier for statins was elevated apolipoprotein B (ApoB) levels or low-density lipoprotein cholesterol (LDL-c) levels. In the intermediate FRS group, 91% met criteria for statin therapy based on the presence of a coronary artery calcification (CAC) score0 or an elevated high-sensitivity C-reactive protein. Male sex, hypertension, elevated ApoB, and a CAC score0 were the factors most strongly associated with indication for statin therapy.Statin therapy is suboptimal in IA despite a significant number of patients meeting indication based on lipoprotein thresholds or CAC scores. Understanding the barriers and potential facilitators of implementing and interpreting these CVD screening tools in IA is needed.

The Article Abstract is not available.

ObjectiveTofacitinib (TOF) is an oral, small-molecule drug used for rheumatoid arthritis (RA) treatment and is one of several alternative treatments to tumor necrosis factor inhibitors (TNFi). We evaluated physician- and patient-reported effectiveness of TNFi compared to TOF, using real-world data from the Ontario Best Practices Research Initiative (OBRI).MethodsPatients enrolled in the OBRI initiating TOF or TNFi between 2014 and 2019 were included. Patients were required to have physician- and patient-reported effectiveness outcome data, including Clinical Disease Activity Index (CDAI) and RA Disease Activity Index (RADAI), available at treatment initiation and 6 (± 2) months later. To deal with confounding by indication, we estimated propensity scores (PS) for covariates.ResultsFour hundred nineteen patients were included. Of those, 226 initiated a TNFi and 193 TOF, and had a mean (SD) disease duration of 8.0 (8.7) and 12.6 (9.6) years, respectively. In addition, the TNFi group was less likely to have prior biologic use (21.7%) compared to the TOF group (67.9%). The proportion of patients in CDAI low disease activity (LDA)/remission (REM) at 6 months was 36.7% and 33.2% in the TNFi and TOF groups, respectively. The generalized linear mixed models adjusting for PS quantile showed that there was no significant difference in CDAI LDA/REM (odds ratio [OR] 0.85, 95% CI 0.51–1.43) and RADAI coefficient (OR 0.48, 95% CI –0.18 to 1.14) between the 2 groups (ref: TOF).ConclusionIn patients with RA, physician- and patient-reported effectiveness are similar in the TNFi and TOF groups 6 months after treatment.

Objective The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic. Methods Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student’s paired two-sample t-tests and McNamar’s tests were performed for continuous and categorical variables between time periods. Results The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7 (12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P Conclusion In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.

ObjectiveTo compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts.MethodsThe 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998–2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively.ResultsIn total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57–5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01–4.67), and second bDMARD or tsDMARD (range 3.71–4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18–40%) or dual therapy (34%, range 29–42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10–32%), dual therapy in 49% (range 39–56%), and bDMARD or tsDMARD in 24% (range 15–28%). The first bDMARD was an anti–tumor necrosis factor in 79% (range 78–82%).ConclusionCanadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

Objectives Time to discontinuation of biologic therapy may be related to mechanism of action. We aimed to compare discontinuation of tumor necrosis factor inhibitors (TNFi) versus non-TNFi in an observational rheumatoid arthritis cohort. Methods Patients enrolled in the Ontario Best Practices Research Initiative (OBRI) starting biologic agents on or after 1st January 2010 were included. Time to discontinuation due to (1) any reason, (2) any of lack/loss of response, adverse events (AEs), physician, or patient decision, (3) lack/loss of response, and (4) AEs were assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results A total of 932 patients were included of whom 174 (18.7%) received non-TNFi and 758 (81.3%) received TNFi. Over a median follow-up of 1.7 years, discontinuation was reported for 416 (44.6%) due to any reason, 367 (39.4%) due to any of lack/loss of response, AEs, physician, or patient decision, 192 (20.6%) due to lack/loss of response, and 102 (10.9%) due to AEs. After adjusting for propensity score, there was no significant difference in discontinuation between the two classes due to any reason [HR 1.14 (0.90–1.46), p = 0.28], lack/loss of response [HR: 1.01 (0.70–1.47), p = 0.95], and AEs [HR: 1.06 (0.64–1.73), p = 0.83]. Similar results were found in biologic naive patients. Conclusions This analysis demonstrates that discontinuation of therapy is similar in patients started on TNFi and non-TNFi therapies. There was also no significant difference in stopping due to lack/loss of response or AEs, suggesting that these reasons should not drive the selection of one treatment over another.

Medical cannabis is often used to alleviate common symptoms in patients with chronic conditions. With cannabis legalisation in Canada and easier access, it is important that rheumatologists understand its potential impact on their practice. Among patients attending rheumatology clinics in Ontario we assessed: the prevalence of medical cannabis use; symptoms treated; rheumatologists' perceptions.Eight rheumatology clinics recruited consecutive adult patients in a 3-part medical cannabis survey: the first completed by rheumatologists; the second by all patients; the third by medical cannabis users. Student's t-test and Chi-square test were used to compare medical cannabis users to never users.799 patients participated, 163 (20.4%) currently using medical cannabis or within2 years and 636 never users; most had rheumatoid arthritis (37.8%) or osteoarthritis (34.0%). Compared to never users, current/past-users were younger; more likely to be taking opioids/anti-depressants, have psychiatric/gastrointestinal disorders, and have used recreational cannabis (p0.05); had higher physician (2.9 vs. 2.1) and patient (6.0 vs. 4.2) global scores, and pain (6.2 vs. 4.7) (p0.0001). Pain (95.5%), sleeping (82.3%) and anxiety (58.9%) were the most commonly treated symptoms; 78.2% of current/past-users reported medical cannabis was at least somewhat effective. Most rheumatologists reported being uncomfortable to authorise medical cannabis, primarily due to lack of evidence, knowledge, and product standardisation.Medical cannabis use among rheumatology patients in Ontario was two-fold higher than that reported for the general population of similar age. Use was associated with more severe disease, pain, and prior recreational use. Reported lack of research, knowledge, and product standardisation were barriers for rheumatologist use authorisation.

The Clinical Disease Activity Index (CDAI) is routinely used in clinical care when treating-to-target RA patients. Previous validation studies have looked at CDAI's overall performance; this analysis aimed at evaluating its properties by disease state and identifying drivers of variance.RA patients enrolled in the OBRI registry, with available follow-up of ≥6 months were included. Construct validity of CDAI was assessed with principal component analysis; internal consistency with Cronbach's alpha (α); correlational validity with Spearman's rho (ρ); agreement in disease state classification with the kappa statistic. Stratification by disease states was performed.CDAI correlation with DAS28 was strong when CDAI10 (ρ=0.79), moderate when CDAI≤10 (ρ=0.56) or 2.8CDAI≤10 (ρ=0.44), and very weak when CDAI≤2.8 (ρ=0.02). Classification agreement of low disease activity (LDA)/remission between CDAI (≤10) and DAS28 (≤3.2) or HAQ-DI (≤2) was fair-to-moderate, while poor-to-fair for remission. For CDAI10, CDAI was able to be reduced to a single component with patient global assessment (PtGA) having the lowest loading. When CDAI≤10, two distinct components were identified: (1) PtGA and physician global assessment; (2) SJC28 and TJC28. Moderate levels (α=0.71) of internal consistency were observed when CDAI10 but low when CDAI≤10 (α=0.23), 2.8CDAI≤10 (α=-0.42) or CDAI≤2.8 (α=-0.35). PtGA showed lowest correlation with remaining CDAI components.CDAI and DAS28 correlated well in moderate/high disease activity and poorly in LDA/remission. PtGA correlated weakly with other CDAI components and had a stronger influence on CDAI in LDA/remission. Thus, careful interpretation of PtGA is necessary when making treatment decisions, particularly in patients in CDAI LDA who are non-remitters.

Objective.Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort.Methods.Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression.Results.Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55–1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50–1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24–0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed.Conclusion.Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.

Objective: For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease-modifying anti-rheumatic drugs (cs- DMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. Methods: Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for all patients and those initiating their first bDMARD/tsDMARD. All TNFi therapies were included. Non-TNFi included Abatacept, Rituximab, Tocilizumab, and Tofacitinib. Results: A total of 1,057 patients were included, of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/ts- DMARD-naïve patients. In 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. Conclusion: This descriptive analysis of data from the OBRI cohort reveals that TNFi are still used in the majority of cases; however, there has been an increase in the use of non-TNFi therapies both overall and as first-line advanced therapy. This trend towards non-TNFi therapies as first-line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line to any of the advanced therapeutics.

Peronia J. Fleming, 1822 is an eupulmonate slug genus with a wide distribution in the Indo-Pacific Ocean. Currently, nine species are considered as valid. However, molecular data indicate cryptic speciation and more species involved. Here, we present results on a new species found in the Persian Gulf, a subtropical region with harsh conditions such as elevated salinity and high temperature compared to the Indian Ocean. Peronia persiae sp. nov. is described based on molecular, histological, anatomical, micro-computer tomography and scanning electron microscopy data. ABGD, GMYC and bPTP analyses based on 16S rDNA and cytochrome oxidase I (COI) sequences of Peronia confirm the delimitation of the new species. Moreover, our 14 specimens were carefully compared with available information of other described Peronia species. Peronia persiae sp. nov. is distinct in a combination of characters, including differences in the genital (ampulla, prostate, penial hooks, penial needle) and digestive systems (lack of pharyngeal wall teeth, tooth shape in radula, intestine of type II).

ObjectivesRA patients are often not in remission due to patient global assessment of disease activity (PtGA) included in disease activity indices. The aim was to assess the lag of patient-reported outcomes (PROs) after remission measured by clinical disease activity index (CDAI) or swollen joint count (SJC28).MethodsRA patients enrolled in the Ontario Best Practices Research Initiative registry not in low disease state at baseline with at ≥6 months of follow-up, were included. Low disease state was defined as CDAI ≤ 10, SJC28 ≤ 2, PtGA ≤ 2cm, pain score ≤ 2cm, or fatigue ≤ 2cm. Remission included CDAI ≤ 2.8, SJC28 ≤ 1, PtGA ≤ 1cm, pain score ≤ 1cm, or fatigue ≤ 1cm. Time to first low disease state/remission based on each definition was calculated overall and stratified by early vs established RA.ResultsA total of 986 patients were included (age 57.4 (12.9), disease duration 8.3 (9.9) years, 80% women). The median (95% CI) time in months to CDAI ≤ 10 was 12.4 (11.4, 13.6), SJC28 ≤ 2 was 9 (8.2, 10), PtGA ≤ 2cm was 18.9 (16.1, 22), pain ≤ 2cm was 24.5 (19.4, 30.5), and fatigue ≤ 2cm was 30.4 (24.8, 31.7). For remission, the median (95% CI) time in months to CDAI ≤ 2.8 was 46.5 (42, 54.1), SJC28 ≤ 1 was 12.5 (11.4, 13.4), PtGA ≤ 1cm was 39.6 (34.6, 44.8), pain ≤ 1cm was 54.7 (43.6, 57.5) and fatigue ≤ 1cm was 42.6 (36.8, 48). Time to achieving low disease state and remission was generally significantly shorter in early RA compared with established RA with the exception of fatigue.ConclusionTime to achieving low disease state or remission based on PROs was considerably longer compared with swollen joint count. Treating to a composite target in RA could lead to inappropriate changes in DMARDs.

Background Patients with rheumatoid arthritis (RA) have increased cardiovascular (CV) and mortality risk. Patients with RA are also frequently prescribed glucocorticoids (GCs) which have been associated with increased risk of mortality. In addition, for patients who have concomitant diabetes mellitus (DM), GCs are known to worsen glycaemic control and hence may further increase CV and mortality risk. This study aimed to understand the relationship between GCs, DM and mortality in patients with RA. Methods This was a retrospective cohort study of patients with incident RA identified from UK primary care electronic medical records. Patients with linkage to Office for National Statistics (ONS) for mortality data (N = 9085) were included. DM was identified through Read codes, prescriptions and blood tests, and GC use was identified through prescriptions. Mortality rate ratios (RR) and rate differences (RD) were calculated across the different exposure groups. Cox proportional hazards regression models were used to estimate interaction on the multiplicative and additive scales. Results In those without DM GC use had a 4.4-fold increased all-cause mortality RR (95% confidence interval (CI): 3.77 to 5.07) compared to non-use, whilst those with DM had a lower RR for GC use (2.99 (95% CI: 2.32, 3.87)). However, those with DM had a higher RD associated with GC use because of their higher baseline risk. In those with DM, GC use was associated with an additional 44.9 deaths/1000 person-years (pyrs) (95% CI: 32.9 to 56.8) compared to non-use, while in those without DM GC use was associated with an additional 34.4 deaths/1000 pyrs (95% CI: 30.1 to 38.7) compared to non-use, while in those without DM GC use was associated with an additional 36.2 deaths/1000 pyrs (95% CI: 31.6 to 40.8). A similar pattern was seen for CV mortality. The adjusted Cox proportional hazards model showed no evidence of multiplicative interaction, but additive interaction indicated a non-significant increased risk. For CV mortality there was no interaction on either scale. Conclusions GC use was associated with higher mortality rates in people with comorbid DM compared to people without DM, despite apparently reassuring similar relative risks. Clinicians need to be aware of the higher baseline risk in patients with DM, and consider this when prescribing GCs in patients with RA and comorbid DM.

International audience; Energy is considered a significant factor for sustainable development, and governments are faced some challenges such as the expenses involved in running the economy and how to perform such costs for reducing the energy intensity and provide energy efficiency. This article investigates government expenditure impact on the energy intensity on top ten European crude oil-exporting countries during 1995-2014. The results confirm the non-linear effect of government expenditure per GDP on the energy intensity with one threshold parameter. Findings indicate that government expenditure impact per GDP on energy intensity is significantly negative at low government expenditure (at first regime) and positive at the high government expenditure (at second regime). The positive and increasing effect of government expenditure on the energy sector in the second regime shows that the government intervention at macro-programs and the high government size can hike up energy intensity.

Despite the availability of treatment guidelines and effective treatments, real-world effectiveness remains suboptimal partly due to poor patient medication adherence. We evaluated a comprehensive set of sociodemographic, health insurance, and disease-related factors for association with patient decision to discontinue anti-rheumatic medications (ARMs) in a large observational RA cohort in Ontario, Canada. Patients from the Ontario Best Practices Research Initiative registry were included. The following predictors of ARM discontinuation were evaluated with cox-regression: patient age, gender, education, income, smoking, health insurance type/coverage, RA duration, erosion presence, RF positivity, DAS28-ESR, physician global, HAQ-DI, comorbidity number, ARM types, and physician characteristics (gender, academic position, urban vs. rural, distance from patient's residence). Patients (1762) were included with a mean (SD) age of 57.4 years (13.0). Approximately 80% were female, 29% had early (≤ 1 year) RA, and 70% were RF-positive. Mean (SD) baseline DAS28-ESR and HAQ-DI were 4.5 (1.5) and 1.2 (0.76), respectively. In multivariate analysis, married status (HR [95%CI] 0.73 [0.56-0.96]), RF positivity (0.73 [0.56-0.96]), and higher comorbidity number (0.92 [0.85-0.99]) were significant predictors of ARMs continuation while higher physician global (1.10 [1.04-1.15]), NSAID use (1.75 [1.29-2.38]), and number of ARMs (1.23 [1.07-1.40]) were associated with ARMs discontinuation. In a subset analysis assessing conventional or biologic DMARD discontinuation, higher HAQ-DI and biologic use over time were associated with lower hazard for discontinuation. Several sociodemographic, disease, and treatment parameters were identified as independent predictors of patient discontinuation of ARMs. These results should be considered when developing patient adherence support programs and in the choice of treatment regimens.

Background:Previous studies have shown that early diagnosis and treatment of rheumatoid arthritis (RA) is important for achieving comprehensive disease control and have identified established disease as an independent predictor of worse clinical outcomes. However, it is not clear whether these differences are driven by patient-reported or objective outcome measures.Objectives:The aim of this analysis was to compare the time to achieving low disease activity (LDA) and remission based on both objective and patient-reported outcomes in people with early vs. established RA followed in routine clinical care.Methods:RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) registry that were not in a low disease state at baseline based on the CDAI, SJC28, PtGA, pain and fatigue criteria below, and had at least six months of follow-up, were included in the analysis. LDA was defined as CDAI≤10, SJC28≤2, TJC28≤2, PtGA≤2cm, pain≤2cm, fatigue≤2cm, and MDGA≤2cm; remission was defined as CDAI≤2.8, SJC28≤1, TJC28≤1, PtGA≤1cm, pain≤1cm, fatigue≤1cm, and MDGA≤1cm. Between group (early vs. established) differences in time to first LDA/remission were assessed with Kaplan-Meier survival analysis and the log-rank test.Results:A total of 986 patients were included, 347 (35%) with early RA and 639 (65%) with established RA. At baseline, patients with early RA were significantly younger (55.8 vs. 58.3 years) and were less likely to have a comorbidity (94.5% vs. 97.5%) or an erosion (26.7% vs. 62.6%), be RF-positive (65.6% vs. 74.2%), use bDMARDs (7.5% vs. 26.6%), and be non-smokers (38.9% vs. 47.3%).Time to achieving LDA based on CDAI (HR [95%CI]: (1.23 [1.07,1.43]), SJC28 (1.32 [1.15,1.51]), TJC28 (1.18 [1.02,1.36]), MDGA (1.28 [1.10,1.49]), PtGA (1.23 [1.05,1.44]), and pain (1.29 [1.09,1.52]) were significantly shorter in early RA compared to established RA. Similarly, time to achieving remission based on CDAI (HR [95%CI]: (1.50 [1.22,1.84]), SJC28 (1.35 [1.17,1.55]), MDGA (1.25 [1.06,1.47]), PtGA (1.22 [1.02,1.47]), and pain (1.37 [1.14,1.65]) were significantly shorter in early RA. However, no differences were observed in time to remission based on TJC28 (1.12 [0.96,1.31]) and either LDA or remission based on fatigue (LDA (1.10 [0.94,1.30]); remission (1.09 [0.92,1.31]).Adjustment for age, gender, presence of comorbidities, and baseline scores did not alter the results.Conclusion:Time to achieving low disease state or remission based on various objective and patient-reported measures is significantly shorter in early compared to established RA with the exception of fatigue.Disclosure of Interests:Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Mohammad Movahedi Consultant of: Allergan, Emmanouil Rampakakis: None declared, Angela Cesta: None declared, John Sampalis: None declared, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

Background: Rheumatoid Arthritis (RA) is a chronic disease that requires regular follow-ups over time. Physicians make treatment adjustments based on their evaluation of disease status and patients’ response to treatment while patients’ perception of disease activity may change over time. Objectives: we aimed to assess the discrepancy between patient global assessment of disease activity and physician assessment of disease activity at baseline and after one year in patients with early RA. We also evaluated factors affecting this discrepancy at these two time points. Methods: Patients enrolled in the Ontario Best Practices Research Initiative (OBRI), a prospective observational cohort of patients with RA who had disease duration of Results: A total of 460 patients with early RA were analyzed. Majority were female (72.4%) with mean (± SD) age of 57 years (±0.6). the discordance rate was 109 (24%) and 99 (21%) at baseline and one year, respectively. In the majority of the discordant cases, PTGA was higher (98 (90%) at baseline and 85 (86%) at one year). Discordant patients had significantly higher fatigue score, health assessment questionnaire disability index (HAQ-DI), pain score, PTGA, MDGA, tender join, composite measures of disease activity and higher number of comorbidities at baseline. Multivariable regression analysis showed that the higher PTGA is significantly associated with higher SJC, TJC and fatigue both at baseline and one year and with higher pain score only at one year. Similar associations were found for MDGA except fatigue which was not significant. Multivariable regression analysis showed that the higher discrepancy between PTGA and MDGA is associated significantly with lower SJC (β=-2.75), higher TJC (β=1.17), and higher fatigue (β=0.85) at baseline. At one-year follow-up, higher pain was the strongest factor (β=4.99) for affecting the higher PTGA-MDGA discrepancy compared with SJC (β=-1.65) and fatigue (β=1.24). Conclusion: Significant discrepancy between PTGA and MDGA exists in about a quarter of patients with early RA at baseline and slightly less after one year. In the majority of these patients PTGA is higher over time. The number of active joints affects both assessments and this effect persists at one year. Clinicians should consider the above associations when makin Acknowledgement: OBRI-RA Investigators: Drs. Ahluwalia, V., Ahmad, Z., Akhavan, P., Albert, L., Alderdice, C., Aubrey, M., Aydin, S., Bajaj, S., Bensen, B., Bhavsar, S., Bobba, R., Bombardier, C., Bookman, A., Cabral, A., Carette, S., Carmona, R., Chow, A., Ciaschini, P., Cividino, A., Cohen, D., Dixit, S., Haaland, D., Hanna, B., Haroon, N., Hochman, J., Jaroszynska, A., Johnson, S., Joshi, R., Kagal, A., Karasik, A., Karsh, J., Keystone, E., Khalidi, N., Kuriya, B., Larche, M., Lau, A., LeRiche, N., Leung, Fe., Leung, Fr., Mahendira, D., Matsos, M., McDonald-Blumer, Midzic, I., Milman, N., H., Mittoo, S., Mody, A., Montgomery, A., Mulgund, M., Ng, E., Papneja, T., Pavlova, P., Perlin, L., Pope, J, Purvis, J., Rohekar, G., Rohekar, Ruban, T., S., Samadi, N., Shaikh, S., Shickh, A., Shupak, R., Smith, D., Soucy, E., Stein, J., Thompson, A., Thorne, C., Wilkinson, S.g treatment decisions. Disclosure of Interests: Pooneh Akhavan: None declared, Mohammad Movahedi: None declared, 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

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:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment as an alternative option to biologic disease modifying antirheumatic drugs (bDMARDs) including tumor necrosis factor inhibitors (TNFi).Objectives:We aimed to evaluate physician and patient reported effectivness outcomes in TNFi compared to TOFA, using real-world data from the Ontario Best Practices Research Initiative (OBRI).Methods:RA patients enrolled in the OBRI initiating their TOFA or TNFi (Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab, and Biosimilars) between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Patients were required to have physician and patient reported effectivness outcomes data available at treatment initiation and 6-month (± 2 months) follow-up. These included clinical disease activity index (CDAI), rheumatoid arthritis disease activity index (RADAI), HAQ-DI, sleep problem, and anxiety/depression scores. Multiple imputation (Imputation Chained Equation, N=20) was used to deal with missing data for covaraites at treatment initiation. To deal with confounding by indication, we estimated propensity scores for covariates with an absolute standard difference greater than 0.1 between the two treatment groups.Results:A total of 419 patients were included. Of those, 226 were initiating a TNFi and 193 TOFA, and had a mean (SD) disease duration of 8.0 (8.7) and 12.6 (9.6) years, respectively. In the TNFi group, 81.9% were female and mean age (SD) at treatment initiation was 56.6 (13.4) years. In the TOFA group, 85% were female and mean (SD) age at treatment initiation was 60.3 (11.2) years. The TNFi group was less likely to have prior biologic use (21.7%) compared to the TOFA group (67.9%). At treatment initiation, physical function measured by HAQ-DI was significantly lower in TNFi compared to the TOFA group (1.2 vs.1.4).The rate of CDAI LDA/remission at 6 months was 36.7% and 33.2% in TNFi and TOFA group, respectively. The generalized linear mixed models (GLMM) adjusting for propensity score quantile, showed that there was no significant difference in CDAI LDA/remission (ORs: 0.85, 95% CI: 0.51, 1.43), RADAI (coefficient: 0.48, 95% CI: -0.18, 1.14), HAQ-DI (coefficient: -0.01, 95% CI: -0.18, 0.16), sleep problems (coefficient: -0.25, 95% CI: -0.95, 0.45), and anxiety/depression scores (coefficient: 0.12, 95% CI: -0.35, 0.58) between the two treatment groups (TOFA used as reference).Conclusion:In this real-world data study, we found that, physician and patient reported effectivness outcomes are similar in the TNFi and TOFA groups 6 months after treatment initiation in patients with RA.Disclosure of Interests:Mohammad Movahedi: None declared, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm. Speaker Honoraria Agreements: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis. Consulting Agreements/Advisory Board Membership: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Claire Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Aurora, Bristol-Meyers Squibb, Celgene, Hospira, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB. Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

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.

Background:Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities with no agreement on which disease measures best predict radiographic progressionObjectives:We aimed to determine which disease activity measures including disease activity score (DAS), modified (M) DAS28 (CRP), clinical disease activity index (CDAI), and health assessment questionnaire disability index (HAQ-DI) best predict rapid radiographic progression (RRP) in early RA patients at baseline (BL) and 3 months.Methods:PREMIER data, a 2-year, multicenter, double-blind active comparator–controlled study with methotrexate (MTX) naïve RA patients and active disease 3.5 at month 12. Logistic regression analysis assessed impact of measures at BL and 3 months on RRP at 12 months. Best cut-off points of M-DAS28(CRP) was also estimated using area under the receiver operating characteristic curve.Results:149 patients were included: female (n=113; 75.8%), positive RF (n=127; 85.2%), mean (SD) age 52.9 (13.3) years, disease duration 0.8 (0.9) year, DAS28(CRP) 6.3 (0.9). After adjusting for potential confounders, only M-DAS28(CRP) at BL (adjOR=3.29; 95% CI: 1.70-6.36) and 3 months (adjOR=2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28(CRP) 4.5 and 2.6 at BL and 3 months maximized sensitivity and specificity for prediction of RRP.Conclusion:M-DAS28(CRP) was a stronger predictor at BL and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from DAS28(CRP) improves prediction of RRP.References:[1] Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis and rheumatism. 2006;54(1):26-37.Acknowledgments :The authors wish to knowledge AbbVie Canada Inc. for providing patients data.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Deborah Weber: None declared, Pooneh Akhavan: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB

Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment and is prescribed alone or with methotrexate (MTX). Tofa can be used as an alternative to biologic disease modifying antirheumatic drugs (bDMARDs) including tumor necrosis factor inhibitors (TNFi).Objectives:We aimed to evaluate the discontinuation rate of this drug, with and without concurrent MTX in comparison with TNFi, in patients with RA in the Ontario Best Practices Research Initiative (OBRI).Methods:RA patients enrolled in the OBRI initiating their TOFA or TNFi (adalimumab, certolizumab, etancercept, golimumab, and infliximab) within 30 days prior to or any time after enrolment between 1stJune 2014 (TOFA approval date in Canada) and 31stDec 2018 were included. Time to discontinuation (due to any reason) were assessed using Kaplan-Meier survival (adjusted for propensity score using inverse probability of treatment weight) to compare patients with and without MTX use at initiation of TOFA or TNFi.Results:A total of 565 patients initiated TOFA (n=208) or TNFi (n=357). Of those, 106 (51%) and 222 (62%) were treated with MTX in the TOFA and TNFi group, respectively and mean (SD) disease duration were 13.1 (9.4) and 9.5 (9.4) years. In the TOFA group, 86% were female and mean (SD) age at treatment initation was 60.4 (10.6) years. In the TNFi group 82% were female and mean age (SD) at treatment initation was 57.0 (12.6) years. The TOFA group was more likely to have prior biologic use (61.5%) compared with the TNFi group (31%). At treatment initiation, the mean (SD) clinical disease activcity index was 24.8 (12.1) in the TOFA group and 21.8 (12.0) in the TNFi group.Over a mean of 17.3 month follow-up, discontinuation was reported in 75 (36%) and 103 (29%) of all TOFA and TNFi patients, respectively. After adjusting for propensity score, patients treated with TNFi and MTX remained on treatment longer than those treated without MTX (Logrank p=0.002) while there was no significant difference in TOFA discontinuation in patients with and without MTX (Logrank p=0.31).Conclusion:In this real world data study, we found that TOFA retention is similar in patients with and without MTX, while patients treated with TNFi and MTX remained on treatment longer than those treated without MTX. Merging data with other RA registries in Canada is proposed to increase study power and to provide more robust results.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

Background:Treat-to-target recommendations for rheumatoid arthritis (RA) dictate that remission or low disease activity should be aimed. Although numerous composite indices are available, the clinical disease activity index (CDAI) is commonly used in routine clinical care due to its simplicity and non-reliance on acute phase reactants.Objectives:The purpose of this analysis was to evaluate the CDAI properties both cross-sectionally and longitudinally in a cohort of RA patients followed in Canadian routine care.Methods:RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI), with available follow-up for ≥6 months and data on CDAI, disease activity score based on 28 joints (DAS28), health assessment questionnaire (HAQ), and ACR/EULAR Boolean remission were included. For both the CDAI score and its change from baseline to 6 months, construct validity was assessed with principal component analysis, internal consistency with the Cronbach’s alpha coefficient (α), correlational validity with the Spearman’s rho coefficient, agreement in disease state classification with percent concordant pairs and the kappa statistic. Stratified analysis by presence of CDAI low disease activity (LDA) or remission was performed.Results:1,582 patients met the inclusion criteria. Principal component analysis showed that CDAI could be reduced to a single component when CDAI is >10 with SJC28 accounting for most variance in score and patient global assessment (PtGA) the least; whereas, when CDAI is ≤10, two distinct components were identified, the first comprising PtGA and physician global assessment (PhGA) and the second SJC28 and TJC28. In terms of internal consistency, high levels were observed for both CDAI at baseline (α=0.83) and its change from baseline to 6 months (α=0.81); however, the consistency between CDAI components was very low when CDAI is ≤10 (α=0.23).Overall, a strong positive correlation was observed between CDAI and DAS28 (rho=0.86) and their changes (rho=0.87) while its correlation with HAQ was weak. When stratifying by CDAI levels, the correlation of CDAI with DAS28 was moderate when CDAI is ≤10 and very weak when CDAI is ≤2.8. Similarly, agreement in the classification of LDA between CDAI and DAS28 or HAQ was fair to moderate, and agreement in classification of remission was poor to fair.Conclusion:CDAI and DAS28 correlate well when disease activity is moderate or high and poorly in LDA or remission. PtGA had a stronger influence on CDAI at LDA or remission state compared to moderate or high disease state. Thus, careful interpretation of PtGA is necessary particularly in patients who are identified as CDAI non-remitters.Disclosure of Interests:Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion,Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, LillyPharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work., John Sampalis: None declared, Emmanouil Rampakakis: None declared

Background:Description of disease activity status in patients with rheumatoid arthritis (RA) at fixed points in time modelled as continuous (e.g. number of swollen joints counts), dichotomous variable (e.g. remission or low disease status using composite measures) do not reflect the patient’s disease course in chronic and relapsing RA.Objectives:We proposed to describe the longitudinal disease activity trajectories for patients with early and established RA over two years’ follow-up in routine clinical care.Methods:RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) with available DAS28-ESR over two years of follow-up were included. Using a latent growth curve modelling (LCGM), subgroups of patients following distinct pattern of DAS28-ESR change over time were identified. Fit statistics and model selection was based on Bayesian information criterion (BIC).Results:A total of 1273 patients were included, 454 (36%) with early RA and 819 (64%) with established RA. At baseline, patients with early RA were significantly younger (57.3 vs. 59.1 years) and with higher DAS28-ESR (4.6 vs. 4.3), and were less likely to have an erosion (25.0% vs. 59.7%), to be RF-positive (70.3% vs. 76.8%), and to use biologic DMARDs (7.0% vs. 29.2%).In patients with early RA (Figure 1A), three subgroups of patients were identified by LCGM with a better fit (BIC: -3070.84). Almost 88% patients with moderate disease activity reached remission (group 1: 48.4%) or low disease status (group 2: 39.3%) after two years, while 12% of patients with high disease profile remained in a moderate state (group 3).Figure 1.Observed and fitted trajectories from the latent growth curve analysis in patients with early and established RA.In patients with established RA (Figure 1B), seven subgroup of patients were identified by LCGM with a better fit (BIC: -5378.13). After two years’ follow-up, 37.5% of patients in remission or low disease state at baseline remained or reached to remission (group 1 and 2, respectively). Two groups of patients with high disease activity at baseline had an improvment after two years (17.3% reached remission and 9.3% reached moderate state; group 5 and 7, respectively). 16.5% of patients with high disease activity at baseline remained in high disease status after two years (group 4 and 6). 19.4% of patients with moderate activity at baseline remained in a moderate state after two years (group 3).Conclusion:Disease course is different between early and established RA. While 70% of early RA patients with moderate or high disease profiles reached remission, only 17% of established patients with high disease activity achieved remission after two years of follow-up. These findings suggest the potential effects of receiving early treatment and health care. The impact of sociodemographic, clinical and medication profile on disease course will be examined as future work for this study.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Xiuying Li: None declared, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

Objective(s)This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice.MethodsPatients with RA enrolled in the Ontario Best Practices Research Initiative registry, with ≥1 swollen joint, autoantibody information and ≥1 follow-up assessment were included. Sustained clinical remission was defined as Clinical Disease Activity Index (CDAI) ≤2.8 in at least two sequential visits separated by 3–12 months. Time to sustained remission was assessed using cumulative incidence curves and multivariate cox regression.ResultsAmong 3251 patients in the registry, 970 were included, of whom 262 (27%) were ACPAneg/RFneg, 60 (6.2%) ACPApos /RFneg, 117 (12.1%) ACPAneg/RFpos and 531 (54.7%) ACPApos /RFpos at baseline. Significant between group differences were observed in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02) and Health Assessment Questionnaire (p=0.002), with ACPApos patients being youngest with lowest disease activity and disability. No difference in biologic use was found between groups (20.2% of patients).Over a mean follow-up of 3 years, sustained remission was achieved by 43.5% of ACPApos/RFpos patients, 43.3% of ACPApos /RFneg patients, 31.6 % of ACPAneg/RFpos patients and 32.4% of ACPAneg/RFneg patients (p=0.01). Significant differences were observed in CDAI improvement based on ACPA and RF status where ACPApos/RFpos had a shorter time to achieving sustained remission (HR 1.30; 95% CI 1.01 to 1.67) and experienced significantly higher improvements compared with ACPAneg/RFneg patients.Conclusion(s)Combined ACPA and RF positivity were associated with improved and faster response to antirheumatic medications in patients with RA.

Background Glucocorticoids (GC) are widely used to treat rheumatoid arthritis (RA), however they are known to have risks associated with them. It has been shown that GCs increase the risk of diabetes mellitus (DM). A few studies have investigated the long-term effects of GC use on outcomes in DM, but not in RA specifically. As people with RA already have increased risk of cardiovascular (CV) disease, the additional burden of DM and GCs may be important. If the effect of GCs was dependent on DM we would say there is effect modification and this can be on the additive scale, corresponding to variation in the absolute treatment effect, e.g. the risk difference (RD), across DM status, or the multiplicative scale, corresponding to variation in the relative treatment effect e.g. the rate ratio (RR).1 Objectives To examine in patients with RA 1) whether all-cause and CV mortality rates differ by GC and DM status, and 2) whether DM modifies the relationship between GC and all-cause and CV mortality on multiplicative and additive scales. Methods Patients with RA and linkage to mortality data were identified from the Clinical Practice Research Datalink (n=9085), a database of primary care electronic medical records in the UK. RR and RD for ever GC use were calculated by DM status. Cox proportional hazards (PH) regression models were fitted with an interaction term for DM and use of GC to assess multiplicative interaction. Additive interaction was measured with the Relative Excess Risk due to Interaction (RERI)2 where a value different from zero indicates a difference in the absolute effect of treatment. Results Those with DM and ever treated with GCs had a 3-fold increased all-cause mortality RR (95% CI: 2.27, 4.09) whilst those without DM had a slightly higher RR (3.46 (95% CI: 2.95, 4.07)). However those with DM had a higher RD: 36.46 deaths per 1000 patient years (pyrs) (95% CI: 27.5, 45.41) compared to those without DM: RD 22.83 deaths per 1000 pyrs (95% CI: 19.83, 25.82) because of higher baseline mortality rates. A similar pattern was seen for CV mortality. The adjusted Cox PH model for all-cause mortality showed no evidence of multiplicative interaction, but there was significant additive interaction (RERI 0.86 (95% CI: 0.18, 1.54)). For CV mortality there was no interaction on either scale. Conclusions Methodologically, this study showed assessing interaction on the additive and multiplicative scales can lead to different conclusions and should be considered carefully. In this study significant interaction was seen on additive scale but not on the multiplicative scale due to higher baseline rates in patients with DM. Clinically, this study provides some evidence that long-term GC therapy may be particularly harmful in patients with RA and DM. References [1] VanderWeele TJ, Knol MJ. A tutorial on interaction. Epidemiologic Methods2014;3(1):33–72. [2] Li R, Chambless L. Test for additive interaction in proportional hazards models. Annals of epidemiology2007Mar;17(3):227–236. Disclosure of Interest None declared

Background Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area which, in turn, can affect the real-world effectiveness of anti-rheumatic medications. Objectives We aimed to describe differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residence in urban vs. rural areas. Methods RA patients enrolled in the OBRI initiating their first bDMARD within 30 days prior to or anytime following enrolment were included in the analysis. Patients excluded if they had less than 2 years of follow-up and less than 2 visits during this period of time. Patients characteristics included sociodemographics (age, gender, race, education level, marital status, smoking status, annual household income, health insurance coverage), disease duration, disease severity parameters (Disease Activity Score (DAS), Clinical Disease Activity Index (CDAI), Swollen and Tender Joints (SJC28, TJC28), Physician Global Assessment (PhGA), Patient Global Assessment (PGA), Health Assessment Questionnaire – Disability Index (HAQ-DI), presence of erosion), bDMARD type, and concomitant anti-rheumatic medications including conventional synthetic disease modifying antirheumatic drug (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and oral steroids. Results A total of 629 RA patients were included of whom 522 (83%) resided in urban areas and 107 (17%) in rural areas. Other than marital status (urban vs. rural: 64.6% vs. 82.2% married; p Conclusions Important differences may exist in the profiles of RA patients initiating their first bDMARD, and residing in rural versus urban areas. The implications on treatment outcomes should be assessed. Disclosure of Interest R. Joshi Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, M. Movahedi Employee of: OBRI, E. Rampakakis Employee of: JSS Medical Research, C. Thorne Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, A. Cesta Employee of: OBRI, J. Sampalis: None declared, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant for: Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Background Positive anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) are included among the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA). Previous studies have shown that autoantibodies are positive predictors of response in RA patients treated with some biologics whereas other studies suggest worse prognosis if positive for ACPA and RF. Objectives The purpose of this study was to evaluate the interaction of RF and ACPA in predicting sustained clinical response in a large observational registry of RA patients followed in routine practice. Methods RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) registry, with active disease (≥1 swollen joint), available autoantibody information, and at least 1 follow-up assessment were included in the analysis. Sustained clinical remission was defined as CDAI ≤2.8 in at least 2 sequential visits separated by at least 3 and maximum of 12 months. Time to sustained remission was assessed by plotting cumulative incidence curves and multivariate cox regression. Results A total of 970 (30%) out of 3251 patients in the registry were included, of whom 262 (27%) were anti-CCPneg/RFneg, 60 (6.2%) anti-CCPpos/RFneg, 117 (12.1%) anti-CCPneg/RFpos, and 531 (54.7%) anti-CCPpos/RFpos. At baseline, significant differences were observed between groups in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02), and HAQ-DI (p=0.002), with anti-CCPpos/RFpos and anti-CCPpos/RFnegpatients being youngest and having the lowest disease activity and disability. No differences were observed in terms of biologic use (20.2% of patients). Sustained remission was 10% more likely if anti-CCPpos, and was achieved by 43.5% of anti-CCPpos/RFpospatients, 43.3% of anti-CCPpos/RFnegpatients, 31.6% of anti-CCPneg/RFpospatients and 32.4% of anti-CCPneg/RFnegpatients (p=0.01). Significant differences were observed in the time to achieving sustained clinical response from enrolment in the OBRI based on anti-CCP status (p Multivariate cox regression adjusting for baseline CDAI score, age and sex also showed differences between groups; statistically significance in anti-CCPpos/RFpos vs. anti-CCPneg/RFnegpatients (HR [95% CI]: 1.30 [1.01–1.67]; p=0.04). Conclusions These results suggest that anti-CCP but not RF positivity may be associated with a higher chance of remission, possibly due to an improved treatment response. Disclosure of Interest J. Pope Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, M. Movahedi Employee of: OBRI, E. Rampakakis Employee of: JSS Medical Research, A. Cesta Employee of: OBRI, J. Sampalis: None declared, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant for: Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Background: Patients with rheumatoid arthritis (RA) may discontinue their biologic disease modifying antirheumatic drug (bDMARDs) due to non-response, loss of response or adverse events. However, time to discontinuation may be related to mechanism of action. Objectives: We aimed to compare drug survival of tumor necrosis factor inhibitors (TNFi) versus non-TNFi in patients initiating bDMARD treatment in a Canadian (Ontario) observational cohort. Methods: Patients enrolled in the Ontario Best Practice Research Initiative (OBRI) who started bDMARD therapy within 30 days before or any time after OBRI enrolment were included in the primary analysis. Patients were followed from bDMARD start until discontinuation/switching, death, lost to follow-up, or last visit, whichever came first. Time to discontinuation/switching of bDMARD due to (i) any reason, (ii) non-response or loss of response, and (iii) adverse events (AEs), were assessed using Kaplan-Meier survival analysis for TNFi versus non-TNFi users. Results: Among the 943 patients included in the primary analysis, 187 (19.8%) received non-TNFi and 756 (80.2%) TNFi. Mean (SD) age and disease duration were 56.4 (12.7) years and 9.6 (9.8) years, respectively, and the majority were females (79.1%) and biologic naive (84.4%). TNFi included Etanercept, Adalimumab, Certolizumab, Golimumab, and Infliximab; and non-TNFi inlcuded Abatacept, Rituximab, Tocilizumab, and Tofacitinib. Over a mean (SD) follow-up of 2.4 (2.0) years, bDMARD discontinuation/switching was reported for 37.6% of patients, with significant difference in time to discontinuation between TNFi and non-TNFi users (Logrank p=0.01). However, there was no significant difference due to non-response or loss of response (Logrank p=0.67) between the two groups. At 2 years, more patients remained on TNFi (71.0%) compared to non-TNFi (57.0%). At 5 years, 51.0% and 44.0% of patients still remained on TNFi and non-TNFi, respectively. Conclusions: The overall retention rate for biologics was comparable to finding in European registries. We found that patients stay on TNFi longer compared to non-TNFi. However, no significant difference was found between the two groups, for discontinuation or switching of bDMARDs due to non-response or loss of response. Further analyses are required to adjust for the effect of potential confounders (e.g. age, sex, disease activity, and other treatment regimens) on biologic discontinuation. Reference [1]Alejandro Souto Jose Ramon Maneiro Juan J. Gomez-Reino. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology2016March 1;55(3):523–534. Disclosure of Interest: M. Movahedi Employee of: OBRI, S. Couta Employee of: OBRI, A. Cesta Employee of: OBRI, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB, Consultant for: Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

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.

Background Despite the availability of safe and effective treatments and the establishment of treatment guidelines, real-world effectiveness remains suboptimal largely due to low patient adherence with prescribed treatment. Objectives The purpose of this study was to systematically evaluate sociodemographic, health insurance, and disease-related factors associated with patient reported decision for discontinuation of anti-rheumatic medications (ARM) in a large observational cohort of RA patients followed in Canadian routine clinical care. Methods RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) clinical registry and had at least two years of follow-up were included in the analysis. Treatment discontinuation due to patient reported decision was defined as ARM discontinuation. Independent predictors of ARM discontinuation were evaluated with multivariate cox-regression using both time-fixed and time-dependent variables. Factors considered included patient sociodemographics (age, gender, race, education status, annual income, smoking history), health insurance information (private vs. non-private, % coverage), disease parameters (RA duration, presence of erosion, RF positivity, DAS28, physician global, HAQ-DI, number of comorbidities), types of medications used, and physician characteristics (gender, academic position, urban vs. rural, distance from patient9s residence). Results A total of 1,762 patients were included in the analysis with a mean (SD) age of 57.4 (13.0) years and disease duration of 8.5 (9.3) at the time of enrolment to the registry (baseline). The majorities of patients were female (77.7%), had post-secondary education (55.3%), and had private insurance (67.2%). In terms of disease severity, 54.5% had prior erosion, 69.5% were RF positive, and mean (SD) DAS28 was 4.5 (1.5). In a multivariate analysis, married status (HR, 0.73; 95% CI 0.56–0.96), RF positivity (HR, 0.73; 95% CI 0.56–0.96), and higher number of comorbidities (HR, 0.92; 95% CI 0.85–0.99) were identified as significant predictors of ARM continuation while higher physician global score (HR, 1.10; 95% CI 1.04–1.15), NSAID use (HR, 1.75; 95% CI 1.29–2.38), and polypharmacy (HR, 1.23; 95% CI 1.07–1.40) were associated with ARM discontinuation due to patient reported decision. Conclusions In this systematic approach a variety of factors encompassing sociodemographics, disease, and medication characteristics, were identified as significant independent predictors of ARM discontinuation due to patient reported decision. These results should be taken into consideration when developing patient adherence support programs and in the choice of treatment regimens. Disclosure of Interest V. Ahluwalia Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Bristol Myers Squibb, Celgene, Hospira, Janssen, Pfizer, Roche, Sanofi, & UCB, M. Movahedi Employee of: OBRI/JSS, E. Rampakakis Employee of: JSS Medical Research, A. Cesta Employee of: OBRI, X. Li Employee of: OBRI, S. Couto Employee of: OBRI, J. Sampalis Employee of: Head of JSS, C. Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Bristol Myers Squibb, Celgene, Hospira, Janssen, Pfizer, Roche, Sanofi, & UCB

Objectives To investigate the associations between smoking status, smoking cessation and hospitalisations for cardiovascular events (CVE) and respiratory tract infections (RTI) in an inception cohort of patients with rheumatoid arthritis (RA). Methods The study was set within UK primary care electronic health records (the Clinical Practice Research Datalink) linked to hospital inpatient data (Hospital Episode Statistics). Patients with RA were followed from diagnosis to hospitalisation with a record of CVE or RTI, leaving their general practice, death, or 10 January 2012, whichever was earliest. Smoking status (never, current, former) was defined using primary care data and could vary over time. Survival analysis was performed using Cox regression (first event) and conditional risk set models (multiple RTIs). Results 5677 patients were included in the cohort: 68% female, median age 61 years. The age-adjusted and sex-adjusted risks of hospitalisation for CVE or RTI were more than twice as high in current vs never smokers (CVE HR (95% CI) 2.19 (1.44 to 3.31); RTI 2.18 (1.71 to 2.78)). The risks for both outcomes were significantly higher in current compared with former smokers (CVE 1.51 (1.04 to 2.19), RTI 1.29 (1.04 to 1.61)). For each additional year of smoking cessation, the risk of first CVE and RTI hospitalisation fell significantly, approximately 25% and 15% respectively in the adjusted models. Conclusions Patients with RA who smoke have an increased risk of hospitalisation with CVE or RTI compared with never and former smokers. The risk decreases for each additional year of smoking cessation. Patients with RA who smoke should be advised to stop smoking.