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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.

Objective Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities, but there is no agreement on which disease measures best predict radiographic progression. We aimed to determine which disease activity measures, including the disease activity score, the modified disease activity score in 28 joints with C-reactive protein testing (M-DAS28-CRP), the Clinical Disease Activity Index, and the Health Assessment Questionnaire Disability Index, at baseline and 3 months best predicted rapid radiographic progression (RRP) in patients with early RA. Methods Data were used from PREMIER, a 2-year, multicenter, double-blind, active comparator controlled study with methotrexate (MTX)-naive patients with RA and active disease for less than 3 years. Treatments included adalimumab plus oral MTX, adalimumab, or oral MTX. Only patients in the MTX arm were analyzed in this study. RRP was defined as a change in the modified total Sharp score of less than 3.5 at month 12. The logistic regression analysis assessed the impact of measures at baseline and 3 months on RRP at 12 months. Best cutoff points of the M-DAS28-CRP were also estimated by using area under the receiver operating characteristic curve. Results A total of 149 patients were included (female patients: n = 113 [75.8%]; positive rheumatoid factor: n = 127 [85.2%]; mean [SD] age: 52.9 [13.3] years; mean [SD] disease duration: 0.8 [0.9] year; mean [SD] M-DAS28-CRP: 6.3 [0.9]). After adjusting for potential confounders, only the M-DAS28-CRP at baseline (adjusted odds ratio [AOR] = 3.29; 95% confidence interval [CI]: 1.70-6.36) and 3 months (AOR = 2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28-CRP of 4.5 and 2.6 at baseline and 3 months, respectively, maximized positive and negative predictive values for prediction of RRP. Conclusion The M-DAS28-CRP was a stronger predictor at baseline and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from the DAS28-CRP improves prediction of RRP.

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.

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.

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 For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), the next step in goal-directed therapy is initiation of either biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs). bDMARDs include tumour-necrosis factor inhibitors (TNFi) or non-TNFi classes. Since inception of Ontario Best Practice Research Initiative (OBRI), new treatment options have become available Objectives We aimed to describe the evolution of relative use of non-TNFi vs. TNFi in Ontario-based practices from 2008-2017. Methods Adult patients with RA enrolled in the OBRI who started therapy with bDMARDs or tsDMARDs anytime during, or up to 30 days before, enrollment were included. Using descriptive analysis of data from each year between 2008 and 2017, the relative proportion of the population treated with TNFi and non-TNFi therapy was measured for (i) all patients and (ii) those initiating their first bDMARD/tsDMARD. TNFi included: Etanercept, Adalimumab, Certolizumab, Golimumab, and Infliximab. Non-TNFi included: Abatacept, Rituximab, Tocilizumab, and Tofacitinib. Results A total of 1,057 patients were included of whom 653 were bDMARD/tsDMARD naive. In 2008, the relative non-TNFi use was 3/56 (5.4%) in all patients and 0/31 (0%) in treatment-naive patients. By 2013 the proportion non-TNFi use increased to 135/562 (24%) in all patients and 11/92 (12.0%) in treatment-naive patients. This increasing trend in relative non-TNFi utilization continued in both groups until 2016 when relative use was 224/679 (33.0%) in all patients and 17/56 (30.4%) in treatment-naive. This was followed by 144/426 (33.8%) and 4/15 (26.7%), respectively in 2017. Conclusion This descriptive analysis of data from the OBRI cohort shows an increase in the use of non-TNFi therapies. The overall trend towards greater use of non-TNFi therapies as first line agents after combined csDMARDs may be partially explained by the presence of guidelines that allow clinicians to select any of the above options as first line advanced therapies. Future analyses evaluating patient-, disease- and concomitant drug use-specific determinants of physician decision-making will be conducted. Acknowledgement 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. Disclosure of Interests Elliot Hepworth: None declared, Mohammad Movahedi: None declared, Emmanouil Rampakakis : None declared, Reza Mirza: None declared, Arthur Lau: None declared, Angela Cesta: None declared, Janet Pope Consultant for: Eli Lilly and Company, 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 (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

Supplemental Digital Content is available in the text, Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area. We described differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residential area type. Cross-sectional analysis of 793 adult RA patients in the longitudinal Ontario Best Practices Research Initiative (OBRI) registry initiating their first bDMARD

Background:Prior studies have shown that in the real-world setting, rheumatoid arthritis (RA) patients have lower disease activity than those studied in clinical trials. However, randomized controlled trials for biologics continue to mainly recruit patients with severe disease.Objectives:To assess the implications of this practice, our study investigates the proportion of patients achieving remission (DAS28-ESR ≤ 2.6), in RA patients with moderate disease activity and severe disease activity, at 12 months post starting their first biologic, and identifies baseline predictors of biologic response.Methods:This study included RA patients who have never been treated with a biologic and initiated their first biologic while enrolled in the Ontario Best Practices Research Initiative (OBRI) registry, between 2008 and 2019. Patients selected had either moderate RA (DAS28 ≥ 3.2 to ≤ 5.1) or severe RA (DAS28 > 5.1). Comparisons were made between the moderate and severe disease groups using the student’s t-test for continuous variables, and the chi-square test for categorical variables. Multivariable logistic regression was used to test potential predictors of remission. Backward stepwise model selection was applied to select variables with p-value ≤0.10. Multiple imputation (MCMC method; n=20) was used to impute missing data.Results:Overall, 641 patients initiated their first biologic, 483 had follow up data at 12 months (moderate disease activity=264; severe disease activity=219). In the moderate group, the mean age (SD) was 55.7 (13.1) and 80% were female. In the severe group, mean age (SD) was 58.4 (12.3) and 81% were female. At time of biologic initiation, the mean DAS28 for the moderate group was 4.1 (0.5), and 6.0 (0.6) for the severe group. After 12 months of starting a biologic, the proportion of patients achieving remission was 50% in the moderate group, and 23% in the severe group (pp=0.0049). More specifically, the absolute improvement in DAS28 after 12 months was higher in the severe group at 2.2 (1.5), compared to a change of 1.4 (1.3) in the moderate group (pp=0.039), and higher HAQ-DI score (OR 0.49, 95% CI 0.36-0.68; pp=0.0390) was identified as a positive predictor of remission.Conclusion:This prospective cohort study found RA patients with moderate disease activity are more likely to reach targeted states (remission and low disease activity), whereas severe patients have greater absolute improvements in DAS28 and HAQ-DI but are less likely to achieve remission. Moderate disease is a positive predictor for remission, whereas female gender and a higher HAQ-DI score are negative predictors.Table 1.Logistic regression analysis for the rate of achieving DAS28 low disease activity at six months.Moderate-RA(n=264)Severe-RA(n=219)P-ValueRemission, n (%)111 (50)45 (23)Low disease activity, n (%)151 (59)74 (35)Change in DAS from baseline ≥ 1.2, n (%)168 (66)164 (78)0.0049HAQ-DI change >0.22, n (%)98 (53)83 (52)0.7974Change in DAS28 from baseline, mean (SD)-1.4 (1.3)-2.2 (1.5)Change in HAQ-DI from baseline, mean (SD)-0.29 (0.57)-0.30 (0.66)Change in fatigue from baseline, mean (SD)-0.98 (3.2)-1.11 (3.2)Change in sleep from baseline, mean (SD)-0.85 (3.6)-1.05 (3.9)0.0004Disclosure of Interests:Nancy Guo: None declared, Xiuying Li: None declared, Mohammad Movahedi: None declared, Angela Cesta: None declared, 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.Acknowledgment: :Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

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 Collection of Anti-Rheumatic Medication (ARM) information from both patients and rheumatologists is considered a strength for Rheumatoid Arthritis (RA) registries and cohorts. However, it is important to assess the agreement between these two data sources. Objectives We aimed to examine the agreement of ARM use, their administration routes, and start and stop dates between self-reports and rheumatologist reports in the Ontario Best Practices Research Initiative (OBRI). Methods Adult Patients enrolled in the OBRI who consented to both patient interviews and rheumatologist evaluations were included. Patients in the OBRI are interviewed every six months, while rheumatologist assessments are conducted as per routine care. For this analysis, we included patients who enrolled in OBRI on or after Sep 1 st 2010 and compared ARM use reports where rheumatologist visits and interviews occurred within 60 days of each other. ARM included conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) and biologic DMARDs (bDMARDs). Cohens’ Kappa statistics of agreement between the two data sources were calculated. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement. To examine factors associated with agreement, a multivariate backward stepwise logistic regression was used to model the odds of agreement for ARM use. The agreement and absolute time gap (days) for starts and stops dates between self-reports and rheumatologist reports were also assessed and presented by median and interquartile range (IQR) in a subset analysis. Results 2154 patients (78.7% female) were included with a mean (SD) age at OBRI enrolment of 57.8 (12.6) year. Mean (SD) disease parameters were: disease duration: 8.4 years (9.9); DAS28: 4.2 (1.6); physician global: 4.0 (2.5); and health assessment questionnaire (HAQ) disability Index: 1.1 (0.8). For csDMARDs use, the prevalence was 74.2% based on self-reports and 76.6% based on rheumatologist reports. The prevalence of bDMARDs use was approximately 20.0% based on both reports. Overall agreement for ARM use between self-reports and rheumatologist reports was good. In the regression model, increased HAQ-pain index (OR: 0.66; 95% CI: 0.60–0.73) and physician global (OR: 0.95; 95% CI: 0.92–0.98) were significantly associated with the lower agreement. By contrast, post-secondary education (OR: 1.20; 95% CI: 1.02–1.40), and seeing an academic rheumatologist (OR: 1.47; 95% CI: 1.25–1.73) were significantly associated with the higher agreement between two data sources. There was a good and very good agreement for reported administration route of bDMARDs and csDMARDs, respectively. The median absolute time gap (IQR) of start dates and stop dates for ARM use reported by two data sources was 7 days 1–27 and 19 days, 5–48 respectively. Conclusions The results of this analysis suggest that ARM reports from the two data sources have strong agreement in the OBRI. This agreement is even better for patients who have post-secondary education and are being treated by an academic rheumatologist. Disclosure of Interest M. Movahedi Employee of: OBRI, A. Cesta Employee of: OBRI, X. Li 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, Bristol Myers Squibb, Celgene, Hospira, Janssen, Pfizer, Roche, 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 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

Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias—a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81–2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose–response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death. Electronic supplementary material The online version of this article (doi:10.1007/s10654-016-0167-1) contains supplementary material, which is available to authorized users.

Breast cancer (BC) is the most prevalent cancer in Iranian women and the fifth most common cause of cancer-related death in Iran. Among predicting factors and preventive measures for BC, the parity and breastfeeding (BF) are controversial issues. We therefore conducted this case–control study to find out the relation of parity and BF to incidence and risk of BC. A structured questionnaire that covered demographic criteria and BC risk factors was completed for case (376 cases) and control (425 subjects) groups, both matched in terms of demographic variants, reproductive issues, and socioeconomic status. Odds ratio (OR) and 95% confidence intervals (CI) were computed as measures of association from the logistic models. All p values reported are two-sided. Parity significantly reduces the risk of BC (p

Payesh2010; 9: 83-89Accepted for publication: 1 March 2009[EPub a head of print-3 November 2009] Objective(s): This study was conducted for external evaluation of one intervention that has been carried out by traffic police. In this study the efficacy of provisional driver licensing on reducing traffic injuries and the intensity of injuries (fatal or non-fatal) was investigated.Methods: Data on traffic accidents and injuries from one year before till two years after the implementation of provisional driver licensing were obtained from traffic police data base. After data cleaning and stratification traffic injuries and mortalities, the implementation of graduate driver licensing compared in those in early years of their driving experience.Results: Drivers under 23 years of age consisted 22.8% of total road traffic injuries (RTIs) in the year prior to the implementation of graduate driver licensing. This proportion reduced to 15.5% and 16.1% in the first and second year after implementation, respectively, among holders of provisional B1 type driver license (P

BACKGROUND: For more than three decades, the main health indicators of the rural population of Iran have been gathered using a 'vital horoscope'. In this study, we use information derived from the vital horoscope to assess trends over time and geographic patterns of inequality in these health indicators. METHODS: Nine main health indicators were derived from official annual reports of the Ministry of Health & Medical Education from 1993 to 2005. Having plotted their temporal variations, we modelled their patterns and predicted their values for 2006 and 2007 using linear regression and fractional polynomial regression models. In order to illustrate spatial variations, we normalized the provincial indicators and mapped their geographical variations in two time bands: 1996-2000 and 2001-05. RESULTS: Neonatal mortality rate (NMR), infant mortality rate (IMR) and under-5 mortality rate (U5MR) had a decreasing trend between 1993 and 2005. However, the slop for NMR (beta = -0.26) was much smaller than the slopes for IMR (beta = -1.16) and U5MR (beta = -1.60), thus the rate of decline for NMR was less. The percentage of births attended by unskilled personnel declined from 27.2 to 7.5%, and the maternal mortality rate (MMR) declined from 47 to 34 deaths per 100 000 live births. At a provincial level, the heterogeneity in some indicators decreased (e.g. unskilled attendance at birth, IMR and total fertility rate), while we found no substantial changes in others. CONCLUSION: Our findings indicate a remarkable improvement in most of the health indicators in rural areas. On the other hand, there is still considerable inequality among the rural population at a provincial level.

Objective To quantify the risk of incident diabetes mellitus (DM) associated with the dosage, duration, and timing of glucocorticoid (GC) use in patients with rheumatoid arthritis (RA). Methods We undertook a cohort study using 2 databases: a UK primary care database (the Clinical Practice Research Datalink [CPRD]) including 21,962 RA patients (1992–2009) and the US National Data Bank for Rheumatic Diseases (NDB) including 12,657 RA patients (1998–2013). Information on the dosage and timing of GC use was extracted. DM in the CPRD was defined using Read codes, at least 2 prescriptions for oral antidiabetic medication, or abnormal blood test results. DM in the NDB was defined through patient self-reports. Data were analyzed using time-dependent Cox models and a novel weighted cumulative dose (WCD) model that accounts for dosage, duration, and timing of treatment. Results The hazard ratio (HR) was 1.30 (95% confidence interval [95% CI] 1.17–1.45) and 1.61 (95% CI 1.37–1.89) in current GC users compared to nonusers in the CPRD and the NDB, respectively. A range of conventional statistical models consistently confirmed increases in risk with the GC dosage and duration. The WCD model showed that recent GC use contributed the most to the current risk of DM, while doses taken >6 months previously did not influence current risk. In the CPRD, 5 mg of prednisolone equivalent dose for the last 1, 3, and 6 months was significantly associated with HRs of 1.20, 1.43, and 1.48, respectively, compared to nonusers. Conclusion GC use is a clinically important and quantifiable risk factor for DM. Risk is influenced by the dosage and treatment duration, although only for GC use within the last 6 months.

Purpose In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). Patients and Methods Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. Results During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). Conclusion Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

Background Guidelines support the use of combination conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs), switching csDMARDs and/or use of biologic DMARDs (bDMARDs) treatment in active rheumatoid arthritis (RA) after use of methotrexate (MTX). Objectives The purpose of this study was to determine treatment practices after use of MTX in patients with RA who were on either monotherapy or combination csDMARDs in a large observational cohort (OBRI) in order to determine contemporary practice where use of bDMARDs from government coverage is restricted to active RA (+RF and/or +ACPA) or erosions, SJC≥5 with MTX failure, combination failure (triple csDMARDs: MTX + hydroxychloroquine + sulfasalazine) or use of leflunomide. Methods Patients enrolled in OBRI with documented MTX failure defined as discontinuation due to side effect, primary/secondary failure, or patient/physician decision. Demographics and disease parameters at MTX failure were compared between monotherapy failures, double therapy (Rx) failures, and triple Rx failures. Results A total of 313 patients with MTX failure were included with a mean (SD) age of 58.8 (13.2) years and disease duration of 6.7 (8.2) years. Of these, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) were double (MTX +1 csDMARD) Rx, and 55 (17.6%) were on triple or more (MTX + multiple csDMARDs)Rx, respectively, at the time of MTX failure. At the time of MTX failure disease duration was numerically higher in patients failing monotherapy and double Rx as compared to triple Rx (7.5 vs. 6.8 vs. 4.5 years, respectively; P=0.276) while patients failing triple Rx were more likely to have an erosion (43.1% vs. 37.2% vs. 61.8%; P=0.009) and had significantly higher patient global (3.5 vs. 3.9 vs. 4.8; P=0.046). When looking at patient transition to csDMARDs monotherapy, csDMARDs combination Rx or bDMARDs treatment, patients receiving monotherapy were more apt to have switches to other monotherapy (87% of patients), whereas those on combination Rx received more combination csDMARDs (78% and 74% of patients on MTX + 1 csDMARDs or MTX + multiple csDMARDs, respectively) and bDMARDs combination Rx (21% and 26%, respectively)(Figure 1). Conclusions There are inherent differences in the selection of subsequent treatment regimen between patients failing MTX monotherapy vs. MTX combination therapy. Overall, the results of the current analysis suggest the use of a sequential treatment intensification strategy in routine clinical practice in Ontario. Disclosure of Interest None declared

Background The Ontario Best Practices Research Initiative (OBRI) collects data on RA treatment in a real-world setting. Patients are enrolled and prospectively followed to assess among other things, response to biologic Disease-Modifyng Antirheumatic Drugs (bDMARDs) and conventional synthetic Disease-Modifying Antirheumatic Drug (csDMARD) therapy. Objectives The objective of this study was to look at a real-world population and determine if initial disease activity influences the durability of the first used biologic in RA treatment. Methods bDMARD-naive RA patients were included if they started a biologic at baseline or at any time after entry into OBRI. For initial DAS, we used the DAS28 value between 6 months before and 3 months after the start of the first biologic, whichever was closer to the date of biologic use. Patients were censored at date of first biologic, or at date of last follow-up after initiation, whichever occurred first. Analysis was performed for all years of follow up, and also censored at 1.5 years (for investigating initial DAS impact). Persistence was defined as the length of time the patients continued to receive the drug, irrespective of change in dose, route, or addition of any other csDMARD or steroids. If the drug was stopped for 5.10). Survival was compared using KM curves. Results 563 patients were included. At 1 year, the survival probability was 0.78. The median survival of biologic was 57.8 (95% Confidence Interval: 42.2) months and with a mean survival of 44.5 (SE: 1.5) months. Patients who were on biologic monotherapy, with no concomitant csDMARD use, has worse persistence of their initial biologic. Figure 1 shows the KM Plot of survival on biologic stratified by DAS28. Despite the initial trend towards better survival associated with lower initial DAS, this was not statistically significant. Similarly, type of insurance (public/private) did not impact biologic survival. As seen in other studies, the only factor to impact longer persistence on initial biologic was use of a csDMARD with the bDMARD. Conclusions Early/initial DAS28 score did not impact patients9 persistence on their initial bDMARD, nor did insurance type. This suggests that initial DAS28 score does not influence the durability of the first bDMARD in active RA. Combination of csDMARD and bDMArD was more durable than bDMARD monotherapy. Disclosure of Interest None declared

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Based on the latest Iranian national cancer department report, the total number of women registered with breast cancer was 6976 cases during 2007. Five year survival is one of the indicators used for evaluation of the quality for care to different types of malignancies including breast cancer. OBJECTIVES: The aim of this study was to estimate survival rate of breast cancer in 6147 Iranian patients at a national level in different geographic regions. MATERIALS AND METHODS: 6147 cases of breast cancer, which had telephone number and were diagnosed between 2001-2006, were called to obtain information about their life status. Survival estimates were calculated using the Kaplan-Meier method, and the survival probability was calculated for the overall cohort and in different categories of gender, age and pathologic type of tumor. Hazard ratios (HR) according to demographic and risk variables were calculated by Cox's proportional hazard model. RESULTS: The overall 5-year survival rate was 71.0%. The mean survival time was different between men and women, which was statistically significant. The number of men involved with breast cancer was 172 (2.8%) of all cases. The 5-year survival rate for patients in age group 41-50 years was significantly higher than other age groups (P = 0.001). The likelihood of death was higher in patients with 61 years old or more years rather than those below forty years old (HR = 1.31; 95% CI: 1.12-1.55). CONCLUSIONS: THE FINDINGS OF THIS STUDY MIGHT HELP IRANIAN HEALTH MANAGERS: 1) to be more conscious about geographical and regional determinants which will affect overall survival rate. 2) To carry preventive activities such as public education particularly in Iranian men. 3) To think about screening and early detection of breast cancer.

The recent significant improvement in most health indicators in Iran has not been explored deeply particularly in comparison with other countries in Eastern Mediterranean Region (EMR). We aimed to explore the temporal variations of five main indicators in Iran and compare their variations in EMR countries.Data on DPT vaccination and birth weight were obtained from EMR office reports, and total fertility rate, under 5 mortality rate (U5MR) and adult literacy rate (ALR) were obtained from WHO sources for the time period 1995-2005. Using linear regression, we modeled the temporal variations in Iran and other EMR countries classified by their human development index (HDI) levels.The estimated annual decline rate of U5MR in Iran as a middle HDI country was 2.5 per 1000 live birth which was much greater than the corresponding number in countries with medium HDI (1.85) and very close to countries with high HDI (2.67). The WHO data showed that Iran was very successful in increasing ALR.It seems that most health indicators in Iran have improved more rapidly compared with countries with low and medium HDI in EMR. The improvement rates were also very close to countries with high HDI in the region.

Background Oral glucocorticoids (GCs) are commonly used to treat rheumatoid arthritis (RA) with GC prescriptions often issued in primary care. Some general practitioners (GPs) may have a greater tendency to prescribe GCs, which could affect the likelihood of a patient receiving a GC prescription. Patient characteristics such as age and comorbidities may influence GC prescribing differently, depending on GC prescribing tendency. Objectives To a) determine whether GC prescribing tendency influences GC prescriptions for RA patients and b) whether baseline patient characteristics affect GC prescribing differently in patients seen by prescribers with high vs low GC prescribing tendencies. Methods Patients with incident RA during a defined follow up period were identified from the Clinical Practice Research Datalink, a large UK general practice database. The primary (i.e. most frequent) prescriber of all medications was determined for each patient. For each primary prescriber, the mean proportion of time their patients spent on GCs during follow up was calculated. The median of these values was used as a cut-off for “low” or “high” GC prescribers. Logistic regression was used to determine the effect of prescriber tendency on the likelihood of receiving a GC prescription during follow up and to test the interaction between prescriber tendency and a range of baseline patient characteristics, including patient demographics, comorbidities that are also indications for GC use and known steroid-related comorbidities. Results 16 536 patients with RA were identified and 3270 GPs were assigned as primary prescribers. The mean proportion of time their patients spent on GCs ranged from 0 to 100% (median 10.2%, IQR 0.1%– 24.4%), and GPs were categorised as ‘high’ prescribers if their patients spent a mean of ≥10.2% of follow-up on GCs. 6,372 (38.5%) patients were assigned a “low” GC prescriber and 10,164 (61.5%) were assigned a “high” GC prescriber. The odds of a patient receiving a GC prescription during follow up was 3.1x greater if they were seen by a “high” GC prescriber compared to a “low” GC prescriber (95%CI 2.88-3.29). The probability of receiving a GC prescription increased with age, but the effect differed significantly between the prescriber groups: OR 1.14 (95%CI 1.10, 1.18) per decade in the “low” GC prescriber group, OR 1.27 (95% CI 1.23-1.30) in the “high” GC prescriber group. Baseline comorbidities that influenced the probability of receiving a GC prescription and that were significantly different between GC prescriber groups were asthma (“low” OR 2.65 CI 2.29-3.06, “high” OR 1.76 CI 1.57-1.98) lower respiratory tract infection (“low” OR 1.75 CI 1.53-2.00, “high” OR 1.45 CI 1.31-1.61), hypertension (“low” OR 1.21 CI 1.03-1.42, “high” OR 1.30 CI 1.18-1.43), and inflammatory bowel disease (“low” OR 0.85 CI 0.46-1.56), “high” OR 1.92 CI 1.21-3.06). Conclusions Prescriber tendency towards high GC use was associated with an increased likelihood of RA patients receiving GCs. The effect of certain patient characteristics on GC prescription differed according to prescriber tendency. Disclosure of Interest None declared

Introduction The efficacy of provisional driver licensing and mandatory seat belt use legislations on reducing traffic injuries and the intensity of injuries was investigated. Methods Data on traffic crashes and injuries from 1 year before till 2 years after the implementation of provisional driver licensing and mandatory seat belt use legislations were obtained from traffic police. Data of traffic injuries and mortalities from 1 year before till 2 year after the implementation of graduate driver licensing compared in those in early years of their driving experience. To evaluate the efficiency of mandatory seat belt use legislation the intensity of traffic injuries were compared. Results Drivers under 23 years of age consisted 22.8% of total crashes in the prior to the implementation of graduate driver licensing. This proportion reduced to 15.5% and 16.1% in the first and second year after implementation, respectively, in holders of provisional B1 type driver license. This approximately 7% reduction in total accident was statistical significant (p Conclusion It is suggested that both interventions were efficient in reduction of intensity of traffic injuries and provisional driver licensing was efficient in reducing the crude number of traffic injuries.

Background Glucocorticoid (GC) therapy is used by more than one in two patients with Rheumatoid Arthritis (RA)[1][1]. GCs are effective [2][2] but have side effects including Diabetes Mellitus (DM) [3][3]. Objectives The aim of this retrospective cohort study was to quantify the risk of incident type II DM in patients with RA treated with oral GCs, and its relationship with dose. Methods Adult patients with RA were identified from a large UK primary care research database, the Clinical Practice Research Database (CPRD) using a validated algorithm during the study period 01/92-12/09. Patients with prevalent DM at the time of their first code for RA were excluded. GC exposure from first code for RA was considered using several models including a time-varying binary indicator of ever or current use, current daily dose, average daily dose and cumulative dose. Incident DM was defined as a READ code for type II DM, at least two oral anti-diabetic prescriptions or abnormal blood results (blood sugar, HbA1C or glucose tolerance test). Gender, age, BMI, smoking status, family history of DM, hypertension, prior cumulative dose of oral GC, current DMARDs and ever NSAID use were potential confounders. Multiple imputations were used to impute missing data for BMI and smoking status. Incidence rates for type II DM were calculated for different patterns of GC exposure. Crude and adjusted Hazard Ratios (HR) were estimated using Cox regression. Results 23,736 adult RA patients were included. 70% were female with a median age of 59 years (IQR 49-71). Median time at risk per patient was 5.39 years (Range: 0.003-18.0). 2,462 patients were diagnosed with type II DM during follow-up: incidence 14.0 events/1000 person years (pyrs) in unexposed patients and 21.9 events/1000pyrs in time following GC exposure. The crude HR was 1.53 (95%CI 1.41-1.66) in ever GC users compared with non-use. After adjusting for all covariates, the HR reduced to 1.38 (95%CI 1.27-1.51). This equates to one additional case of DM per year for every 185 patients currently receiving GCs. Each 5mg increase of current oral GC was associated with a 14% increased risk of DM (HR:1.14; 95%CI 1.11-1.17). Patients currently taking between 10-30mg/day had an adjusted HR of 1.95 (95%CI 1.62-2.34) compared to non-use, equating to one additional case of DM for every 67 patients treated. A 5mg increase in average daily dose was associated with a 32% increased risk (HR 1.32; 95%CI 1.26-1.39), suggesting prolonged exposure increased risk. Conclusions Oral GC therapy is a significant and clinically important risk factor for incident Type II DM in patients with RA. Screening for DM might be warranted in patients taking oral GC therapy. References 1. Caplan L, Wolfe F, Russell AS, Michaud K. Corticosteroid use in rheumatoid arthritis: prevalence, predictors, correlates, and outcomes. J Rheumatol. 2007;34(4):696-705. 2. Gotzsche PC, Johansen HK. Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. Bmj 1998;316(7134):811-8. 3. Hoes, J. N., M. C. van der Goes, et al. (2011). “Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids.” Annals of the Rheumatic Diseases 70(11): 1887-1894. Disclosure of Interest None Declared [1]: #p-7 [2]: #p-8 [3]: #p-9