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To evaluate a stratified screening process for the early identification of axial spondyloarthritis (SpA) with consideration of the following: 1) wait times from primary care to rheumatology screen, 2) incremental precision and accuracy from primary care to rheumatology screening, and 3) diagnostic delay.Adults with low back pain attending primary care at low back pain clinics prospectively underwent a primary standardized clinical screening. Patients with low back pain of3 months who experienced symptom onset at age50 years were referred for a comprehensive secondary screening by a physical therapist with advanced rheumatology training. At secondary screening, patients with features of inflammation were classified as being at a low, medium, or high risk for axial SpA versus no risk for axial SpA. Precision and accuracy of this screening strata were measured against a rheumatologist with expertise in axial SpA.Overall, 405 patients underwent primary and secondary screening in the present study. The study cohort had a mean ± SD age of 36.9 ± 9.9 years, and 55% were women. HLA-B27 was present in 14.4% of patients. Median wait time from primary screening to secondary screening was 15 days. Axial SpA risk assignment by rheumatologist was 64.9% for no risk or low risk for axial SpA and 35.1% for medium risk or high risk for axial SpA. The best combination of sensitivity (68%), specificity (90%), positive predictive values (80%), and negative predictive values (84%) was evident in the secondary screening. In this cohort, 15.6% of patients received a final diagnosis of axial SpA. Median low back pain duration from symptom onset to diagnosis was 2 years for nonradiographic axial SpA and 7 years for ankylosing spondylitis.A stratified interprofessional screening process can facilitate rapid diagnosis of persistent low back pain with high precision and accuracy in patients who have axial SpA.

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.

Objective To determine the contribution of rheumatoid arthritis (RA) to conditions and medical events. A secondary objective is to quantify this association before and after the introduction of biologic medications. Methods All data were collected as health administrative data in Ontario, Canada. Patients with RA (n = 136 678) matched 1:1 to a pool of possible controls without RA from 1995 to 2016. The study was a retrospective longitudinal observational administrative data-based cohort study with cases (RA) and controls (two non-RA comparator groups). The main exposure was new-onset RA identified by a validated diagnosis algorithm. The secondary exposure was the calendar year, which provided a natural experiment to compare years in which biologics were unavailable (pre-2001) to increasing utilization over time. The main outcomes were counts of 27 Johns Hopkins Expanded Diagnostic Cluster Comorbid Conditions. Outcomes were reported as counts and percentage differences between cases and matched controls. Results Patients experienced increases in conditions and medical events up to 5 years before RA disease incidence-4.9 conditions per patient-year compared with 4.6 conditions per patient-year in matched controls. Comorbidities increased to 8.7 conditions per patient-year in the year of RA incidence but were lower in the years after diagnosis-6.9 conditions per patient-year at 5 years postdiagnosis. Conclusion This study reframes the clinical manifestations of RA with detailed data on the marginal contribution of RA to conditions and medical events. These results show that a large portion of disease burden is due to the indirect effects of RA.

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.

Background Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout. Search methods We updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020. Selection criteria We included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol. Two trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias. Moderate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16). More participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal. Moderate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded for indirectness and imprecision). Participants on lesinurad in the original study continued (CONT) on the same dose. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution; 43/65 in the lesinurad 400 mg CONT arm compared to 38/64 in the lesinurad 200 mg CONT arm had tophi resolution (RR 1.11, 95% CI 0.85 to 1.46). Lesinurad 400 mg plus febuxostat may result in no difference in adverse events; 57/65 in the lesinurad 400 mg CONT arm had an adverse event compared to 50/64 in lesinurad 200 mg CONT arm (RR 1.12, 95% CI 0.96 to 1.32). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events; 10/65 participants in the lesinurad 400 mg CONT arm withdrew due to an adverse event compared to 10/64 participants in the lesinurad 200 mg CONT arm (RR 0.98, 95% CI 0.44 to 2.20). Lesinurad 400 mg plus febuxostat may result in no difference in mean serum uric acid (sUA), which was 3 mg/dl in the lesinurad 400 mg CONT group compared to 3.9 mg/dl in the lesinurad 200 mg CONT group (mean difference -0.90, 95% CI -1.51 to -0.29). Participants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. Low-certainty evidence downgraded for indirectness and imprecision showed that lesinurad 400 mg (CROSS) may result in tophi resolution (17/34) compared to lesinurad 200 mg (CROSS) (14/33) (RR 1.18, 95% CI 0.70 to 1.98). Lesinurad 400 mg in combination with febuxostat may result in no difference in adverse events (33/34 in the lesinurad 400 mg CROSS arm compared to 27/33 in the lesinurad 200 mg (CROSS); RR 1.19, 95% CI 1.00 to 1.41). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events, 5/34 in the lesinurad 400 mg CROSS arm withdrew compared to 2/33 in the lesinurad 200 mg CROSS arm (RR 2.43, 95% CI 0.51 to 11.64). Lesinurad 400 mg plus febuxostat results in no difference in sUA (4.2 mg/dl in lesinurad 400 mg CROSS) compared to lesinurad 200 mg (3.8 mg/dl in lesinurad 200 mg CROSS), mean difference 0.40 mg/dl, 95% CI -0.75 to 1.55. Authors' conclusions Moderate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.

The evidence assessing the relationship between frailty and risk of adverse health outcomes in patients with rheumatoid arthritis (RA) remains limited and sparse in the literature. Data from the Ontario Best Practices Research Initiative (OBRI), a clinical registry of patients with RA, were used to explore the relationship between frailty and fracture risk in patients with RA. Patients were referred to OBRI by their participating rheumatologist, and contacted by OBRI trained interviewers. Primary outcome was time to first incident osteoporotic fractures during follow-up that led to a hospitalization or emergency room visit. Frailty was measured by a Rockwood-type frailty index (FI) of deficit accumulation that consisted of 32 health-related deficits. To quantify the relationship between frailty and risk of fracture, we used Cox proportional hazards models with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) reported. We included 2923 patients (mean age 57.7 standard deviation [SD]: 12.7; 78% female,) for analyses. During a mean follow-up of 3.7 years, there were 125 (4.3%) incident fractures reported. The FI was significantly higher in patients with a fracture compared to controls (0.24 vs. 0.20, p = 0.02). The FI was found to be significantly related to increased risk of fracture in the fully-adjusted models, with a HR of 1.04 (95% CI: 1.02-1.06, p 0.001) and 1.58 (95% CI: 1.32-1.89, p 0.001) for per-0.01 and per-SD increase in the FI respectively. In summary, our study demonstrates that higher frailty status is significantly related to increased risk of osteoporotic fractures in patients with RA. Quantifying the frailty status as a research tool may aid in fracture risk assessment, management and decision-making in RA.

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.

BACKGROUND CONTEXT Lumbar spinal stenosis (LSS) can impair blood flow to the spinal nerves giving rise to neurogenic claudication and limited walking ability. Reducing lumbar lordosis can increases the volume of the spinal canal and reduce neuroischemia. We developed a prototype LSS belt aimed at reducing lumbar lordosis while walking. PURPOSE The aim of this study was to assess the short-term effectiveness of a prototype LSS belt compared to a lumbar support in improving walking ability in patients with degenerative LSS. STUDY DESIGN This was a two-arm, double-blinded (participant and assessor) randomized controlled trial. PATIENT SAMPLE We recruited 104 participants aged 50 years or older with neurogenic claudication, imaging confirmed degenerative LSS, and limited walking ability. OUTCOME MEASURES The primary measure was walking distance measured by the self-paced walking test (SPWT) and the primary outcome was the difference in proportions among participants in both groups who achieved at least a 30% improvement in walking distance from baseline using relative risk with 95% confidence intervals. METHODS Within 1 week of a baseline SPWT, participants randomized to the prototype LSS belt group (n=52) and those randomized to the lumbar support group (n=52) performed a SPWT that was conducted by a blinded assessor. The Arthritis Society funded this study ($365,000 CAN) with salary support for principal investigator funded by the Canadian Chiropractic Research Foundation ($500,000 CAN for 5 years). RESULTS Both groups showed significant improvement in walking distance, but there was no significant difference between groups. The mean group difference in walking distance was −74 m (95% CI: −282.8 to 134.8, p=.49). In total, 62% of participants wearing the prototype LSS belt and 82% of participants wearing the lumbar support achieved at least 30% improvement in walking distance (relative risk, 0.7; 95% CI: 0.5–1.3, p=.43). CONCLUSIONS A prototype LSS belt demonstrated significant improvement in walking ability in degenerative LSS but was no better than a lumbar support.

Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment as the first or an alternative option to biologic disease- modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi). The similarity in retention of TNFi and TOFA was previously reported separately by the Ontario Best Practices Research Initiative (OBRI) and the Quebec cohort RHUMADATA®.Objectives:To increase the study power, we propose to evaluate the discontinuation rate (due to any reason) of TNFi compared to TOFA, using pooled data from both these registries.Methods:RA patients enrolled in the OBRI and RHUMADATA initiating their TOFA or TNFi between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Time to discontinuation was assessed using adjusted Kaplan-Meier (KM) survival and Cox regression models. To deal with confounding by indication, we estimated propensity scores for covariates with a standard difference greater than 0.1. Models were then adjusted using stratification and inverse probability of treatment weight (IPTW) methods. Multiple imputation (Imputation by Chained Equation method, N=20) was used to deal with missing data for covariates at treatment initiation.Results:A total of 1318 patients initiated TNFi (n=825) or TOFA (n=493) with mean (SD) disease duration of 8.9 (9.3) and 13.0 (10.1) years, respectively. In the TNFi group, 78.8% were female and mean age (SD) at treatment initiation was 57.6 (12.6) years. In the TOFA group, 84.6% were female and mean (SD) age at treatment initiation was 59.5 (11.5) years. The TNFi group was less likely to have prior biologic use (33.9%) than the TOFA group (66.9%). At treatment initiation, the mean (SD) CDAI was significantly (pOver a mean follow-up of 23.2 months, discontinuation was reported in 309 (37.5%) and 182 (36.9%) of all TNFi and TOFA patients, respectively. After adjusting for propensity score deciles across 20 imputed datasets, there was no significant difference in discontinuation between treatment groups (adjusted HRs: 0.96, 95% CI: 0.78-1.18; p=0.69). The results were similar for two propensity adjustment methods. Figure 1 shows IPTW adjusted KM survival curves comparing discontinuation rates in patients treated with TNFi and TOFA.Figure 1.Note: Propensity Score Weighted (IPTW) Survival Curves was performed using one imputed datasetConclusion:In this pooled real -world data study, we found that TNFi and TOFA retention is similar in patients with RA. In the next step we will analysis the data for specific reasons of dicontinutaion. We will also repeat analysis comparing discontinuation in the first users versus those after one or more biologic failure.Disclosure of Interests:Mohammad Movahedi: None declared, Denis Choquette Grant/research support from: Rhumadata® is supported by unrestricted grants from Abbvie Canada, Amgen Canada, Eli Lilly Canada, Novartis Canada, Pfizer Canada, Sandoz Canada and Sanofi Canada., Louis Coupal: 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

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.

Objective To quantify patient preferences for maintenance therapy of Crohn’s disease and understand the impact on treatment selection. Methods We conducted a discrete-choice experiment in patients with Crohn’s disease (n = 155) to measure the importance of attributes relevant to choosing between different medical therapies for maintenance of Crohn’s disease. The attributes included efficacy and withdrawals due to adverse events, as well as dosing and other rare risks of treatment. From the discrete-choice experiment we estimated the part-worth (importance) of each attribute level, and explored preference heterogeneity through latent class analysis. We then used the part-worths to apply weights across each outcome from a prior network meta-analysis to estimate patients’ preferred treatment in pairwise comparisons and for the overall group of treatments. Results The discrete-choice experiment revealed that maintaining remission was the most important attribute. Patients would accept a rare risk of infection or cancer for a 14% absolute increased chance of remission. Latent class analysis demonstrated that 45% of the cohort was risk averse, either to adverse events or requiring a course of prednisone. When these preferences were used in modelling studies to compare pairs of treatments, there was a ≥ 78% probability that all biologic treatments were preferred to azathioprine and methotrexate, based on the balance of benefits and harms. When comparing all treatments, adalimumab was preferred by 53% of patients, who were motivated by efficacy, and vedolizumab was preferred by 30% who were driven by the preference to avoid risks. However, amongst biologic treatment options, there was considerable uncertainty regarding the preferred treatment at the individual patient level. Conclusion Patients with Crohn’s disease from our population were, on average, focused on the benefits of treatment, supporting intensive treatment approaches aimed at maintaining remission. Important preference heterogeneity was identified, however, highlighting the importance of shared decision making when selecting treatments.

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:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment and is prescribed alone or with methotrexate (MTX). We previously reported the similarity in retention between TOFA monotherapy and TOFA with MTX using data from two different registries separately; the Ontario Best Practices Research Initiative (OBRI) and the Quebec registry RHUMADATA.Objectives:To increase the study power, we propose to evaluate the discontinuation rate (due to any reason) of TOFA with and without MTX, using pooled data from these two registries.Methods:RA patients enrolled in the OBRI and RHUMADATA initiating their TOFA between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Concurrent MTX use was defined as MTX use for more than 75% of the time while using TOFA. Multiple imputation (Imputation Chained Equation method, N=20) was used to deal with missing data for covariates at treatment initiation.Time to discontinuation was assessed using Cox regression models. To deal with confounding by indication, we estimated propensity scores for selected covariates with an absolute standard difference greater than 0.1. We then adjusted Cox regression models for propensity quantile to compare the discontinuation of TOFA with MTX versus TOFA without MTX.Results:A total of 493 patients were included. Of those, 244 (49.5%) and 249 (51.5%) were treated with MTX and without MTX, respectively. Compared to TOFA monotherapy, the TOFA with MTX group had a significantly lower mean HAQ-DI, fatigue score, and the number of prior biologic use at the time of TOFA initiation. A lower proportion of positive ACPA (59% vs. 66%), prevalence of hypertension (31% vs 37%), and concomitant use of Leflunomide (11% vs. 23%) were also observed for patients using TOFA with MTX.Over a mean follow-up of 19.0 months, discontinuation was reported in 182 (36.9%) of all TOFA patients. After adjusting for propensity score quantile across 20 imputed datasets, there was no significant difference in discontinuation between treatment groups (adjusted HRs: 1.12, 95% CI: 0.83-1.51; p=0.49).Conclusion:In this pooled real-world data study, we found that in patients with RA, the retention of TOFA is similar if it is used as monotherapy or in combination with MTX.Disclosure of Interests:Movahedi: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by unrestricted grants from Abbvie Canada, Amgen Canada, Eli Lilly Canada, Novartis Canada, Pfizer Canada, Sandoz Canada and Sanofi Canada., Louis Coupal: 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.Acknowledgment: :Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Quantifying the contribution of rheumatoid arthritis to the acquisition of subsequent health care costs is an emerging focus of the rheumatologic community and payers of health care. Our objective was to determine the healthcare costs before and after diagnosis of rheumatoid arthritis (RA) from the public payer’s perspective. The study design was a longitudinal observational administrative data-based cohort with RA cases from Ontario Canada (n = 104,933) and two control groups, matched 1:1 on year of cohort entry from 2001 to 2016. The first control group was matched on age, sex and calendar year of cohort entry (diagnosis year for those with RA); the second group added medical history to the match before RA diagnosis year. The main exposure was new onset RA. The secondary exposure was calendar year of RA diagnosis to compare attributable costs over the study observation window. Main outcomes were health care costs in 2015 Canadian dollars, overall and by cost category. We used attribution methods to classify costs into those associated with RA, those associated with comorbidities, and age/sex-related underlying costs. Health care costs associated with RA increased up to the year of diagnosis, where they reached $8,591: $4,142 in RA associated costs; $1,242 in RA comorbidity associated costs; and $3,207 in underlying costs. In the eighth-year post diagnosis, the RA costs declined to $2,567 while the RA comorbidity associated costs remained relatively constant at $1,142, and the underlying age/sex related cost increased to $4,426. RA patients had lower costs when diagnosed in later calendar years. Our results suggest a large proportion of disease related health care costs are a result of costs associated with RA comorbidities, which may appear many years before diagnosis.

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.

Objective Quality measurement for rheumatoid arthritis (RA) patients has largely focused on care provided by rheumatologists. Our aim was to develop and assess quality measures related to the screening and management of comorbidity in RA patients in primary care. Methods We used the primary care Electronic Medical Record Administrative data Linked Database in Ontario, Canada. We harmonized Canadian general population and RA clinical recommendations to develop and assess screening, process, and outcome measures. For each RA patient, 10 non-RA patients were matched by age and sex. Stratified analyses were performed, comparing patients with RA to those without RA, to assess the performance of quality measures. Results We compared 1,405 RA patients to 14,050 matched non-RA patients (72.8% female; mean age 62.5 years). Compared to non-RA patients, RA patients more frequently had influenza (44.9% versus 40.0%) and pneumococcal (40.4% versus 34.1%) vaccinations and bone mineral density testing (67.4% versus 58.1%). Herpes zoster vaccinations were less frequent among RA patients (13.8% versus 19.5%), as was screening for cervical cancer (58.6% versus 64.0%). No significant differences were observed between RA and non-RA patients in screenings for breast (70.7% versus 73.8%) or colorectal (31.7% versus 34.5%) cancers. Only a quarter of RA patients had a comprehensive cardiovascular risk assessment. No definitive differences were detected in the management of patients who had co-occurring cardiovascular disease or diabetes mellitus. Conclusion For both RA and non-RA patients, compliance with Canadian recommendations for preventive medical services and screening for comorbid conditions in primary care was less than optimal. This indicates key targets for improvement.

Background:Costing studies require long-term follow-up data ideally within a homogenous payment structure without multiple potential insurers. We examined trends in associated costs of rheumatoid arthritis from the public payer’s perspective over time.Objectives:The purpose of this study was to measure the population RA associated direct and indirect health care costs using statistical attribution methods among a population with identical health care coverage.Methods:The study was matched longitudinal study of patients with algorithm defined RA residing in Ontario Canada with an RA diagnosis from 2001-2016 (n=104,933). Cases were matched 1:1 during the year of first diagnosis to 2 distinct control groups without RA. Control group 1 were matched on year of birth, and sex (underlying costs). Control group 2 were matched on year of birth, sex, and medical history. Medical history was measured using The John Hopkins Expanded Diagnostic Clusters, a tool that categorizes people with similar conditions based upon their use of healthcare services (physician visits, hospitalizations, emergency department visits, ambulatory care). After matching, healthcare costs were reported in 2015 Canadian Dollars (CAD) overall and by cost sub-category by exposure group and calendar year before versus after RA diagnosis. RA-associated costs were measured as the difference in costs among RA patients and their corresponding matched comparators.Results:At the year of diagnosis, RA cases were predominantly female (70%, n=72,873), mean year of birth 1950, (SD=17.7, Range=1910-2000), with mean year of diagnosis 2006, (SD=6.3, Range=2001-2016). RA patients experienced inceased indirect cost acquisition compared to the direct costs of RA alone. The health care costs of RA patients were identical to age/sex/medical history matched controls yet rising up until 2 years before RA diagnosis where they diverged from age/sex/disease matched controls $3,585/ptyr compared to $3,352/ptyr. The costs of RA patients were highest $8,468 CAD/ptyr ($888,572,644 total) in the year of diagnosis declining to a steady state by 2 years post diagnosis $7,867/ptyr with a slight increase in costs by 8 years post diagnosis $8,035/ptyr in (Figure 1). Differences age/sex matched controls were detectable throughout the study time period even up to 19-years pre-diagnosis. In the year of diagnosis, the direct costs of RA were $4046/ptyr (8468-4422), while the indirect costs of RA were $1254/ptyr ($4422-$3168) and the underlying age-sex specific costs were $3,168/ptyr. Our analysis suggest that both the direct and inflammatory costs of RA are growing over time compared to matched controls (Figure 1) by year 8 the direct joint-related costs of RA were 2528 (8035-5507) the indirect costs were 1,144 (5507-4363) and the age/sex underlying costs were 4,363.Figure 1.Annual Per-Patient Total Health Care Costs Over Time Grouped by Exposure Before and After Rheumatoid Arthritis DiagnosisConclusion:The costs of RA have grown over time with medications representing a smaller than expected portion of total costs but a large increase in costs relative to matched controls. These results indicate that the direct costs of RA are decreasing over time compared to matched controls at 8 years post diagnosis and that over time, the indirect associated portion of costs remains almost constant, showing that over time the costs of indirectly related issues are becoming a larger proportion of total costs. Methodological advancements in costing attribution over time could contribute to understanding the patterns in health care resource usage among populations with chronic diseases.Disclosure of Interests:Mark Tatangelo: None declared, George Tomlinson: None declared, J Michael Paterson: None declared, Nick Bansback: 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: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.

Objective Our aim was to characterize referrals to rheumatologists, the early care management of patients with rheumatic diseases, and timeliness of care and treatment. Methods We conducted a retrospective observational study involving patients with first-time rheumatology referrals between 2000 and 2013 in the primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Referrals were characterized in terms of diagnoses, patient demographics, diagnostic tests, treatment initiated by family physicians and rheumatologists, and other specialists seen prior to rheumatology consultation. Timeliness of referrals, rheumatologist consultations, and treatment were determined overall and for each diagnostic category. Results Among 2,430 patients referred to a rheumatologist, 69% were female, with an average age of 53 years. The principal diagnosis associated with the referral included osteoarthritis (32%), systemic inflammatory rheumatic diseases (31%), regional musculoskeletal conditions (16%), chronic pain conditions (14%), osteoporosis (2%), and other/miscellaneous (5%). Family physicians most frequently prescribed nonsteroidal antiinflammatory drugs/cyclooxygenase 2 inhibitors (38%), and their pre-referral diagnostic testing practice varied considerably. The duration of time from symptom onset to rheumatology consultation varied by diagnoses, with the shortest being for patients with systemic rheumatic diseases; for rheumatoid arthritis (RA), the median time to consultation was 327 days. Most of the delay occurred prior to referral; 36% of RA patients initiated a disease-modifying antirheumatic drug within 6 months of symptom onset. Conclusion Approximately 1 in 3 referrals to rheumatologists were for a systemic inflammatory rheumatic disease. We observed substantial delays to rheumatology consultations and variations in patterns of care that could be amenable to quality improvement interventions.

Background context Lumbar spinal stenosis (LSS) leads to diminished blood flow to the spinal nerves causing neurogenic claudication and impaired walking ability. Animal studies have demonstrated increased blood flow to the spinal nerves and spinal cord with superficial para-spinal electrical stimulation of the skin. Purpose The aim of this study was to assess the effectiveness of active para-spinal transcutaneous electrical nerve stimulation (TENS) compared to de-tuned TENS applied while walking, on improving walking ability in LSS. Study design This was a two-arm double-blinded (participant and assessor) randomized controlled trial. Patient sample We recruited 104 participants 50 years of age or older with neurogenic claudication, imaging confirmed LSS and limited walking ability. Outcome measures The primary measure was walking distance measured by the self-paced walking test (SPWT) and the primary outcome was the difference in proportions among participants in both groups who achieved at least a 30% improvement in walking distance from baseline using relative risk with 95% confidence intervals. Methods The active TENS group (n = 49) received para-spinal TENS from L3-S1 at a frequency of 65–100 Hz modulated over 3-s intervals with a pulse width of 100–200 usec, and turned on 2 min before the start and maintained during the SPWT. The de-tuned TENS group (n = 51) received similarly applied TENS for 30 s followed by ramping down to zero stimulus and turned off before the start and during the SPWT. Study funded by The Arthritis Society ($365,000 CAN) and salary support for Carlo Ammendolia funded by the Canadian Chiropractic Research Foundation ($500,000 CAN over 5 years). Results From August 2014 to January 2016 a total of 640 potential participants were screened for eligibility; 106 were eligible and 104 were randomly allocated to active TENS or de-tuned TENS. Both groups showed significant improvement in walking distance but there was no significant difference between groups. The mean difference between active and de-tuned TENS groups was 46.9 m; 95% CI (− 118.4 to 212.1); P = 0.57. A total of 71% (35/49) of active TENS and 74% (38/51) of de-tuned TENS participants achieved at least 30% improvement in walking distance; relative risk (RR), 0.96; 95% CI, (0.7 to 1.2) P = 0.77. Conclusions Active TENS applied while walking is no better than de-tuned TENS for improving walking ability in patients with degenerative LSS and therefore should not be a recommended treatment in clinical practice. Registration ClinicalTrials.gov ID: NCT02592642. Registration October 30, 2015.

Background CT-P13, an infliximab biosimilar, has been available in Europe and Canada since 2015, and real-world experience with CT-P13 is important to support the safety of this medication. PERSIST is an ongoing, observational cohort study evaluating CT-P13 as treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a real-world setting. Objectives This interim analysis reports safety outcomes for patients who received CT-P13 as their first biologic (Biologic-naive) or who switched from infliximab reference product (IFX-RP) to CT-P13 (Switched) based on data collected from September 2015 to December 2017. Methods Patients were recruited during usual care at 38 academic and community sites in 6 European countries and Canada. Adult RA, AS or PsA patients prescribed CT-P13 or locally-sourced IFX-RP at the investigator’s discretion and according to the approved label were eligible. Data were analysed descriptively. Results This analysis included 329 patients (RA, n=134; AS, n=110; PsA, n=85). Of these, 6 (1.8%) were not treated, 3 (0.9%) completed study treatment, 244 (74.2%) were ongoing and 76 (23.1%) discontinued study treatment, most commonly due to lack of response (30 [9.1%]). Demographics and baseline characteristics were generally similar between groups (Table 1). Most treatment-emergent adverse events (TEAEs; Table 2) were of mild or moderate intensity; 7/129 events were severe. Most commonly reported adverse events were related to infection (n=33; 10.2%); most frequently reported infection-related TEAEs were nasopharyngitis (n=6; 1.9%), respiratory tract infection (n=5; 1.5%) and pneumonia (n=4; 1.2%). No case of tuberculosis was reported. Eight (2.5%) patients reported infusion related reactions. Conclusion Incidences of TEAEs were similar and there was no discernible pattern across the most common TEAEs between groups. These interim analysis results from the PERSIST study conducted in a real-world setting are consistent with the known safety profile of infliximab and do not demonstrate new safety information to change the benefit−risk profile of CT-P13. Disclosure of Interests Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: AbbVie, Galapagos, Gilead, Eli Lilly, Pfizer Inc, Robin Christensen Grant/research support from: AbbVie Inc, and the Oak Foundation, Speakers bureau: Roche, Shahrzad Moosavi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Selema Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ruffy Guilatco Employee of: Pfizer Inc, Heather Fowler Consultant for: Pfizer UK Limited & Pfizer Inc, 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, Boulos Haraoui Grant/research support from: AbbVie Inc, Merck, and Novartis, Consultant for: AbbVie Inc, Amgen Inc, Eli Lilly, Novartis, Pfizer Inc, and UCB

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

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

Background 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

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

Objective.We evaluated the influence of triage assessments by extended role practitioners (ERP) on improving timeliness of rheumatology consultations for patients with suspected inflammatory arthritis (IA) or systemic autoimmune rheumatic diseases (SARD).Methods.Rheumatologists reviewed primary care providers’ referrals and identified patients with inadequate referral information, so that a decision about priority could not be made. Patients were assessed by an ERP to identify those with IA/SARD requiring an expedited rheumatologist consult. The time from referral to the first consultation was determined comparing patients who were expedited to those who were not, and to similar patients in a usual care control group identified through retrospective chart review.Results.Seven rheumatologists from 5 communities participated in the study. Among 177 patients who received an ERP triage assessment, 75 patients were expedited and 102 were not. Expedited patients had a significantly shorter median (interquartile range) wait time to rheumatologist consult: 37.0 (24.5–55.5) days compared to non-expedited patients [105 (71.0–135.0) days] and controls [58.0 (24.0–104.0) days]. Accuracy comparing the ERP identification of IA/SARD to that of the rheumatologists was fair (κ 0.39, 95% CI 0.25–0.53).Conclusion.Patients triaged and expedited by ERP experienced shorter wait times compared to usual care; however, some patients with IA/SARD were missed and waited longer. Our findings suggest that ERP working in a triage role can improve access to care for those patients correctly identified with IA/SARD. Further research needs to identify an ongoing ERP educational process to ensure the success of the model.

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.

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.

BackgroundLumbar spinal stenosis (LSS) is a growing health problem and a leading cause of disability and loss of independence in older adults. It is usually caused by age-related degenerative narrowing of the spinal canals leading to compression and ischemia of the spinal nerves and symptoms of neurogenic claudication. Limited walking ability is the dominant functional impairment caused by LSS. Animal studies suggest increased blood flow to the spinal nerves and spinal cord with superficial paraspinal electrical stimulation. The purpose of this study is to assess the effectiveness of paraspinal transcutaneous electrical nerve stimulation (TENS) applied while walking on walking ability in patients with LSS.Methods/DesignWe propose to conduct a 2-arm double-blinded (participant and assessor) randomized controlled trial. We will recruit individuals who have limited walking ability due to degenerative LSS from hospital specialists, community physicians, and chiropractors located in the city of Toronto, Canada. Eligible consenting participants will be randomly assigned to either paraspinal TENS or placebo paraspinal TENS applied while walking. The primary outcome will be walking distance measured during a single self-paced walking test. We will calculate the differences in proportions among participants in both groups who achieve at least a 30% improvement in walking distance from baseline using Pearson χ2 test with 95% confidence intervals.DiscussionEffective nonoperative interventions for LSS are unknown. Interventions that can improve blood flow to the spinal nerves while walking may increase walking ability in this population. Transcutaneous electrical nerve stimulation is a low-cost intervention that may have the potential to achieve this objective. To our knowledge, this study will be the first clinical trial to assess the effects of TENS on walking ability of patients with LSS.Trial RegistrationClinicalTrials.gov ID: NCT02592642

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.

A weekly tele-mentoring program was implemented in Ontario to help address the growing opioid crisis through teaching and mentoring family physicians on the management of chronic pain and opioid prescribing. This study assessed opioid prescribing behaviours among family physicians who attended the tele-mentoring program compared to two groups of Ontario family physicians who did not attend the program. We conducted a retrospective cohort study with two control groups: a matched cohort, and a random sample of 3000 family physicians in Ontario. Each physician was followed from one year before the program, which is the index date, and one year after. We examined the number and proportion of patients on any opioid, on high dose opioids, and the average daily morphine equivalent doses prescribed to each patient. We included 24 physicians who participated in the program (2760 patients), 96 matched physicians (11,117 patients) and 3000 random family doctors (374,174 patients). We found that, at baseline, the tele-mentoring group had similar number of patients on any opioid, but more patients on high dose opioids than both control groups. There was no change in the number of patients on any opioid before and after the index date, but there was a significant reduction in high-dose opioid prescriptions in the extension for community healthcare outcomes (ECHO) group, compared to a non-significant increase in the matched cohort, and a non-significant reduction in the Ontario group during the same comparable periods. Participation in the program was associated with a greater reduction in high-dose opioid prescribing.

Prescribing the first biologic treatment for rheumatoid arthritis (RA) is an important decision for patients, their physicians, and payers, with considerable costs and clinical implications. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have known effectiveness and safety profiles and are less expensive; therefore, determining the variables contributing to csDMARD treatment duration is an essential question for patients, physicians, and payers.To describe access to the first biologic DMARD prescription in a population of patients with RA and identical comprehensive health insurance coverage in Ontario, Canada, and to explore the associations of patient, prescriber, and geographic region with differences in time to first biologic prescription.This cohort study of incident patients with RA used administrative data with surveillance and patient-level data collected at yearly intervals. A total of 17 672 patients were included in the study; they were residents of Ontario, Canada, had an incident RA diagnosis at age 67 or older between 2002 and 2015, and received at least 1 csDMARD. Data were analyzed in November 2017.Patient variables were age, sex, disease duration, socioeconomic status, distance to care, and supply of care in the patient's area of residence. Prescriber covariates were year of graduation, specialty of practice, and supply of rheumatologic care in the patient's geographic region.Time from first csDMARD prescription to receipt of first biologic medication.Of 17 672 patients, 11 598 (65.6%) were women, and the mean (SD) age was 75.2 (5.8) years. Characteristics associated with longer time to receipt of a biologic prescription were older age (HR for every 5-year increase, 0.66; 95% CI, 0.62-0.71; P .001), male sex (HR, 0.76; 95% CI, 0.66-0.89; P .001), and distance to the nearest rheumatologist (HR per 10-km increase, 0.99; 95% CI, 0.98-0.99; P .001). Prescribers were primarily rheumatologists (151 of 214 [70.6%]) and primary care physicians (26 of 214 [12.1%]). After adjusting for the number of patients eligible to receive biologic DMARDs, rheumatologists' preferences (ie, yearly prescription rates) for using biologic DMARDs increased over time, from 1.7% in 2001 to 4.9% in 2015. After adjusting for calendar year and patient-, prescriber-, and region-level characteristics, substantial variation between prescribers in rates of prescribing a first biologic DMARD were found (65% variance).This study found variation in time to receipt of first biologic DMARD after prescription of first csDMARD in a population with RA after adjustment for individual-level patient, prescriber, and geographic area covariates, despite identical universal health insurance coverage.

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 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 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.

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

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

The ability to interpret scores from patient-reported outcome measures at the individual patient level depends on the availability of valid, clinically meaningful benchmarks of response and state attainment. The goal was to develop multinational estimates for minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS). A multinational sample of patients with osteoarthritis (OA) was evaluated before and 4 weeks after treatment with nonsteroidal antiinflammatory drugs. Patients completed either the Western Ontario and McMaster Osteoarthritis Index (WOMAC) numerical rating scale 3.1 (hip and knee OA) or the Australian/Canadian Index (AUSCAN) numerical rating scale 3.1 (hand OA) before and after treatment. Patients rated the clinical importance of their response to treatment and their satisfaction with the health state achieved, from which multinational MCII and PASS estimates were calculated for both the WOMAC and AUSCAN indices. A total of 609 patients from 7 countries participated in the study. MCII and PASS estimates varied slightly by instrument and subscale. Absolute (percentage) change for MCII ranged 6-9 (10% to 17%) for WOMAC and 4-9 (8% to 15%) for AUSCAN. PASS estimates ranged 39-48 for WOMAC and 38-45 for AUSCAN. Some between-country variation was observed in MCII and PASS. Preliminary multinational estimates for MCII and PASS have been developed for several countries. Further research is required to evaluate the robustness, temporal consistency, and age- and sex-dependency of the preliminary estimates as well as their generalizability to other countries, languages, cultures, regions, and other condition-specific outcome measures.

Objectives To assess how well treatment recommendations for rheumatoid arthritis (RA) address Grading of Recommendations Assessment, Development and Evaluation (GRADE) steps and determine whether these steps can be adequately appraised using Appraisal of Guidelines Research & Evaluation II (AGREE-II). Study Design and Setting We systematically reviewed English-language treatment recommendations for the pharmacologic management of RA since 2000, assessed how well GRADE steps were addressed, rated AGREE-II quality, and compared the findings. Results GRADE steps were poorly addressed by the 44 included guidelines. Few guidelines discussed study limitations and/or risk of bias (23%), inconsistency (50%), indirectness (39%), imprecision (23%), or potential for publication bias (0%). Observational evidence was cited in 96% but rarely evaluated systematically. Only one guideline considered evidence on patients' preferences for health outcomes, and few provided an explicit justification for the strength of evidence or recommendation. The five GRADE steps that overlapped with AGREE-II questions were addressed more frequently (by 54–100% of guidelines) than the 13 GRADE steps not directly assessed by AGREE-II (0–50%). Among the nine guidelines rated as “Recommended for use” by AGREE-II, 8 of 13 GRADE steps were not addressed consistently by any guideline. Conclusion GRADE's steps are poorly addressed by RA recommendations. AGREE-II provides a broad assessment of quality but lacks sufficient granularity to assess how well a guideline addresses GRADE's steps.

Objective.To develop a Canadian Rheumatoid Arthritis Core Clinical Dataset (CAN-RACCD) to standardize documentation encouraging high-quality care.Methods.A set of candidate elements was drafted through meetings with 27 rheumatologists, researchers, and patients, and supplemented with focused literature reviews. A 3-round online-modified Delphi consensus process was held with rheumatologists (n = 26), allied health professionals (n = 7), and patients (n = 4); for the remainder there was no demographic information. Participants rated both the importance and feasibility of documenting candidate elements on a Likert scale of 1–9, contributed to an online moderated discussion, and re-rated the elements for inclusion in the CAN-RACCD. Elements were included in the final set if importance and feasibility ratings had a median score of ≥ 6.5 and there was no disagreement among participants.Results.Fifty-five individual elements in 10 subgroups were proposed to the Delphi participants: measures of RA disease activity; dates to calculate waiting times, disease duration, and disease-modifying antirheumatic drug start; comorbidities; smoking status; patient-reported pain and fatigue; physical function; laboratory and radiographic investigations; medications; clinical characteristics; and vaccines. All groups were included in the final set, with the exception of vaccination status. Additionally, 3 individual elements from the smoking subgroup were eliminated with a recommendation to record smoking status as never/ever/current, and 2 elements relating to coping and effect of fatigue were eliminated due to low feasibility and importance ratings.Conclusion.The CAN-RACCD stands as a national recommendation on which data elements should be routinely collected in clinical practice to monitor and support high-quality RA care.

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

Objective. To systematically review the evidence on treatment available to prevent an acute attack of gout when initiating a urate-lowering therapy (ULT) and for how long this treatment should be continued. To also evaluate the evidence on the optimal time to start a ULT after an acute attack of gout. Methods. A systematic review as part of the 3e (Evidence, Expertise, Exchange) Initiative on Diagnosis and Management of Gout was performed using Medline, Embase, Cochrane Central Register of Controlled Trials (from 1950 to October 2011), and the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) 2010/2011 meeting abstracts. Two reviewers independently screened titles and abstracts for selection criteria. Included articles were reviewed in detail, and a risk of bias assessment (using the Cochrane tool) was performed. Results. The search identified 8168 articles and 197 abstracts, from which 4 randomized controlled trials were included in the review. Two of these studies compared placebo with colchicine, 1 compared differing durations of colchicine, and 1 compared colchicine with canakinumab. Conclusion. Two randomized controlled trials have shown that colchicine prophylaxis for at least 6 months, when starting a ULT, reduces the risk of acute attacks. Canakinumab, although not currently licensed for gout, has been shown to provide prophylaxis superior to colchicine, when starting a ULT. There is no evidence on the optimum time to start a ULT after an acute gout attack.

OBJECTIVE Patients with rheumatoid arthritis (RA) are at increased risk of TB. Little is known about the risk of nontuberculous mycobacteria (NTM) disease in these patients. We sought to ascertain the rate of NTM infection and TB in all residents of Ontario, Canada, with and without RA. METHODS In a cohort study, all Ontarians aged ≥ 15 years in January 2001 were followed until December 2010. Individuals with RA were identified using a validated algorithm to search hospitalization and physician billing claims. We linked Public Health Ontario Laboratory data to identify all cases of laboratory-confirmed TB and NTM disease. Analysis was performed using Cox proportional hazards regression. RESULTS We identified 113,558 Ontarians with RA and 9,760,075 Ontarians without RA. Relative to the non-RA group, adjusted hazard ratios (HRs) and 95% CIs for TB (1.92, [1.50-2.47]) and NTM disease (2.07, [1.84-2.32]) demonstrated increased risks in the RA group. Among those with RA, per 100,000 person-years, NTM disease (HR, 41.6; 95% CI, 37.1-46.5) was more common than TB (HR, 8.5; 95% CI, 6.5-10.8). After full adjustment, people with RA who developed NTM disease were 1.81 times as likely to die than uninfected people with RA. CONCLUSIONS Mycobacterial infections are more common in Ontarians with RA, with NTM disease more likely than TB. NTM disease is associated with an increased risk of death in patients with RA. Given the rising rates of NTM disease worldwide, determining whether this risk is due to the use of immunosuppressive medications vs RA itself is an important objective for future research.