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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: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

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.

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 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

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