1 Rat Bite Fever Resembling Rheumatoid Arthritis in a 46 Year Old Female



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Objectives: Previous studies have shown that, when sustained good clinical response has been achieved with a biologic therapy, traditional disease-modifying anti-rheumatic drugs (DMARDs) and other treatments can be reduced or discontinued. The aim of this analysis was to assess the discontinuation of concomitant treatment and DMARD tapering in rheumatoid arthritis (RA) patients treated with golimumab (GLM) in Canadian routine clinical practice.  
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, ankylosing spondylitis, psoriatic arthritis with infliximab or GLM as first biologics or after having been treated with a biologic for <6 months. Patients with RA treated with GLM who were enrolled between 2010 and 2014 were included in this analysis. DMARD, steroid and NSAID discontinuation were defined as no use of any drugs in these categories. Time to treatment discontinuation or tapering was assessed both with descriptive statistics and the Kaplan Meier estimator of the survival function. 
Results: 273 RA patients treated with GLM (mean dose = 50 mg s.c. monthly) were included in the analysis; 72.2% were female, mean (SD) age was 57.4 (13.5) years and disease duration was 8.1 (8.6) years. Mean (SD) disease parameters at baseline were: DAS28 = 5.1 (1.7), CDAI = 27.8 (15.9), SJC28 = 7.9 (5.9), TJC28 = 8.9 (7.0), HAQ-DI = 1.3 (0.7), MDGA (0-10 NRS) = 5.5 (2.2), PtGA (mm VAS) = 54.6 (27.9). At baseline, 74.7% were taking concomitant DMARDs, 30.8% were on NSAIDS, and 21.2% on corticosteroid. Mean (SD) available follow-up was 13.8 (9.4) months. Upon treatment with GLM, 11.8% of the patients on a DMARD at baseline discontinued DMARD treatment after a mean (SD) of 15.3 (10.0) months. Furthermore, 56.9% and 86.7% of patients completely discontinued steroid and NSAID treatment after a mean (SD) follow-up of 8.9 (5.4) months and 6.2 (1.3) months, respectively. DMARD dose tapering was documented for 32.4% of patients on DMARDs after a mean (SD) follow-up of 11.2 (8.9) months.
Conclusion: The Results of this Canadian longitudinal observational study have shown that treatment with GLM was associated with discontinuation of concomitant DMARD, steroid, and NSAID treatment as well as DMARD tapering in RA patients. The long-term benefits of this practice for patients have to be determined. 
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Smoking Cessation Measures in Rheumatology Practices: Results from a Self- Reflective Chart Audit
Philip Baer (Private Practice, Scarborough); Jean-Pierre Raynauld (Institut de rhumatologie de Montréal, Montréal); Shelly Dunne (Private Practice, North York); Marie-Anaïs Remillard (Institut de rhumatologie de Montréal, Montréal); Alana Lamb (Janssen, Inc., Toronto); May Shawi (Janssen Inc, Toronto)
Objectives: Smoking is associated with greater disease activity in Rheumatoid Arthritis1, radiographic progression 2, poorer functional status3 and decreased response to therapy4.  The primary objective of this analysis is to look at the change in smoking cessation practices following an educational intervention focused on the implications of smoking in rheumatology patients.
Methods: 50 Rheumatologists will complete a retrospective chart audit on 20 Rheumatoid Arthritis (RA) patients. Physicians will participate in a smoking cessation educative program or review smoking cessation guidelines. A total of 1000 patients will be analyzed. Participating physicians will complete an initial demographic questionnaire followed by a pre-educational intervention survey with a specific focus on a chart review of 10 RA patients who are current smokers. 35-60 days after the educational program, physicians will complete a chart review of 10 different patients who are current smokers. We will analyze the pre-and post-surveys for any changes in practice. We will also look at the proportion of patients with a smoking history (current/former/never/unknown) recorded in their charts, and the proportion of smokers who receive information from the clinician on the effects and impact of smoking on RA and smoking cessation. 
Results: We will share the Results from the smoking chart audit which will be completed in time for presentation at CRA 2016 Annual Scientific Meeting. 
Conclusion: Smoking has negative impacts on disease severity, patient outcomes, radiographic progression and biologic retention in Rheumatology patients. We will share the Results of a self-reflective chart audit that assesses clinician behaviours pre- and post-educational intervention, and the implications these might have for rheumatology practice.   References: 1.  Sokolove J, et al. Smoking status is associated with inflammatory cytokine profile and disease activity: decreased inflammation and disease improvement with smoking cessation?. Arthritis Rheum 2014;66:S146. 2.  Saevarsdottir S, et al. Current smoking status is a strong predictor of radiographic progression in early rheumatoid arthritis: Results from the SWEFOT trial. Ann Rheum Dis 2014 April 4; Epub ahead of print. 3.  Fisher MC, et al. Smoking, smoking cessation, and disease activity in a large cohort of patients with rheumatoid arthritis. J Rheumatol 2012;39:904-9. 4.  Söderlin MK, et al. Smoking at onset of rheumatoid arthritis (RA) and its effect on disease activity and functional status: experiences from BARFOT, a long-term observational study on early RA. Scand J Rheumatol 2011;40:249-55.
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Do Canadian Rheumatologists Actually Treat to Target Once a Biologic has been Initiated? An Analysis from a Prospective, Observational Registry
Philip Baer (Private Practice, Scarborough); Mary Bell (University of Toronto, Toronto); Andrew Chow (Credit Valley Rheumatology, Mississauga); Michael Starr (McGill, Montreal); Boulos Haraoui (Institut de rhumatologie de Montreal, Montréal); Regan Arendse (University of Saskatchewan, Saskatoon); Michelle Teo (n/a, Penticton); Emmanouil Rampakakis (JSS Medical Research, Montreal); John Sampalis (JSS Medical Research Inc, Montreal); Brendan Osborne (Janssen Inc, Toronto); Allen Lehman (Janssen Inc, Toronto); Cathy Tkaczyk (Janssen Inc, Toronto); Francois Nantel (Janssen Inc, Toronto); Karina Maslova (Janssen Inc, Toronto)
Objectives: The objective of this analysis was to assess the frequency and type of treatment optimization in cases where treatment target was not achieved in RA patients initiating treatment with infliximab or golimumab in Canadian routine clinical care.
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, ankylosing spondylitis, or psoriatic arthritis with infliximab, golimumab or ustekinumab. RA patients enrolled during 2002-2014 and with available CDAI information at both months 6 and 12 were included. DA was defined according to the CDAI criteria (remission: ≤2.8; low: >2.8 to ≤10; moderate: >10 to ≤22; high: >22). The association between treatment changes and target achievement was assessed with the Chi-square test.
Results: A total of 498 patients were included, with a mean (SD) age and disease duration of 56.4 (13.2) and 8.6 (8.6) years, respectively. The majority of patients were female (74.1%) and treated with infliximab (74.5%). After 6 months of treatment, 46% of patients had achieved treatment target of remission or low DA, and 54% were still at moderate/high DA. Among the latter, treatment was adjusted in 36.4% and was significantly associated with target achievement at month 12 (46.9% vs. 31%; P=0.009). The frequency of treatment changes by type were: DMARD switch/add-on (11.9% of patients), biologic up-titration (10%), DMARD up-titration (8.2%), steroid initiation (7.8%), NSAID initiation (5.6%), and DMARD initiation (3%). Among patients at moderate/high DA at both visits for whom no treatment adjustment was made, mean (SD) disease parameters at 6 months were: SJC28 = 5.7 (5.0); TJC28 = 8.6 (6.5); MDGA = 3.8 (2.0); PtGA = 4.5 (2.4). Among patients with treatment adjustment: SJC28 = 5.8 (4.2); TJC28 = 9.4 (7.0); MDGA = 4.7 (2.3); PtGA = 5.8 (2.1). Among patients at moderate/high DA at 6 months who achieved target at month 12 without treatment adjustment, disease parameters at month 6 were: SJC28 = 4.7 (4.5); TJC28 = 5.5 (5.1); MDGA = 3.2 (1.7); PtGA = 4.3 (2.5). Among those with a treatment adjustment: SJC28 = 3.5 (3.0); TJC28 = 5.1 (3.3); MDGA = 4.2 (2.2); PtGA = 4.7 (2.8).
Conclusion: These Results suggest that a considerable portion of patients on biologics are not treated to a CRA recommended target in Canada. Treatment adjustment was found to be mainly associated with the physician’s global assessment. PtGA and TJC28 were also significantly higher in those receiving treatment adjustments, while SJC did not correlate with treatment adjustments. 
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The Quality and Continuity of Information Between Primary Care Physicians and Rheumatologists
Jessica Widdifield (McGill University, Montreal); Carter Thorne (Southlake Regional Health Centre, Newmarket); Sasha Bernatsky (McGill University, Montreal); Claire Bombardier (University of Toronto, Toronto); Liisa Jaakkimainen (Institute for Clinical Evaluative Sciences, Toronto); Laura Wing (Institute for Clinical Evaluative Sciences, Toronto); Michael Paterson (Institute for Clinical Evaluative Sciences, Toronto); Debra Butt (University of Toronto, Toronto); Noah Ivers (Women's College Hospital, Toronto); Anne Lyddiatt (Patient Partners in Arthritis, Ingersol); Catherine Hofstetter (Patient Advocate, Toronto); Vandana Ahluwalia (William Osler Health System, Brampton); Karen Tu (Institute for Clinical Evaluative Sciences, Toronto)
Objectives: Good communication is essential to a safe and high-quality referral and consultation process, by providing quality continuity of care, reducing delays in diagnostic processes and repetition of tests, and improving patient and provider satisfaction. Our aim was to evaluate the quality of referral information from family physicians to rheumatologists and the quality and timeliness of consultation information from rheumatologists back to primary care.
Methods: We performed a retrospective chart abstraction study among patients with rheumatology referrals within the primary care Electronic Medical Record Administrative data Linked Database (EMRALD). Using a standardized data abstraction tool, we assessed the completeness and timeliness of referral and consultation letters. Descriptive analyses were performed overall and stratified by diagnoses provided by the rheumatologists.
Results: We identified 2430 referrals from 168 family doctors and 2015 (83%) patients were seen by 146 rheumatologists. Most referrals (2417;99.5%) occurred between 2005-2013. Overall, the family physician stressed an urgent consultation among 211 patients (9%); more frequently among RA and vasculitis patients (21%). Most referral letters (68%) provided details of diagnostic tests (75% labs, 50% imaging, 1% biopsy). Laboratory tests were most frequently provided for systemic inflammatory conditions (89%), with imaging most frequently provided for patients with mechanical/degenerative arthritis (50%). Almost all referral letters (92%) contained details of patient symptoms, with 54% and 21% of patients having documentation of tender and swollen joints, respectively. Only 43% of patients with systemic inflammatory conditions had documentation of symptom duration. For RA patients, 51% had swollen joints according to the referral letter, with 47% having no mention of swollen joints being absent or present. Overall, 69% of consultation letters were returned to primary care within 30 days (target: 100%); 83% within one year. The median (IQR) time to receipt of the consultation letter by family physicians was 19 (2-21) days. Among all 1899 patients with rheumatology consultation letters received post-referral, the rheumatologist initiated treatment among 37% patients within the first year (39% steroid injection, 14% oral steroid, 31% DMARD, 2% biologic). Overall, 93% of consultation letters provided a diagnosis/clinical impression, 92% provided a follow-up plan, 84% specified who was responsible for follow-up, 52% detailed instructions provided to the patient, and 17% mentioned allied health care providers involved in the patient’s care.
Conclusion: Information relayed between family physicians and rheumatologists regarding patient medical histories was reasonably complete, although improvements are needed in the reporting of key triage information for referral letters, and timeliness of receipt of consultation letters.
13
Characterizing Referrals to Rheumatologists to Better Understand Care Management of Patients with Rheumatic Diseases
Jessica Widdifield (McGill University, Montreal); Carter Thorne (Southlake Regional Health Centre, Newmarket); Karen Tu (Institute for Clinical Evaluative Sciences, Toronto); Claire Bombardier (University of Toronto, Toronto); Liisa Jaakkimainen (Institute for Clinical Evaluative Sciences, Toronto); Laura Wing (Institute for Clinical Evaluative Sciences, Toronto); Michael Paterson (Institute for Clinical Evaluative Sciences, Toronto); Noah Ivers (Women's College Hospital, Toronto); Debra Butt (University of Toronto, Toronto); Catherine Hofstetter (Patient Advocate, Toronto); Anne Lyddiatt (Patient Partners in Arthritis, Ingersol); Vandana Ahluwalia (William Osler Health System, Brampton); Sasha Bernatsky (McGill University, Montreal)
Objectives: Primary care physicians play a central role in the early detection and referral for patients with rheumatic diseases. Our aim was to characterize referrals to rheumatologists and investigate diagnostic and treatment patterns prior to after rheumatologist consultation.
Methods: We performed a retrospective chart review and an analysis of structured and semi-structured data within the primary care Electronic Medical Record Administrative data Linked Database (EMRALD), representing comprehensive EMR data from 168 family physicians across Ontario, Canada. We identified patients with first-time rheumatology referrals. Referrals were characterized in terms of patient demographics, provisional diagnoses/clinical impressions, diagnostic tests and treatment, and other specialists seen for the complaint prior to rheumatology consultation.
Results: Among 2430 patients referred to rheumatologists, 69% were female and the mean (SD) age at time of referral was 53 (16) years. Overall, 2417 (99.5%) referrals occurred between 2005 and 2013. Reasons for referrals included: mechanical/degenerative arthritis (787; 32%), systemic inflammatory rheumatic diseases (745; 31%), regional musculoskeletal conditions (395; 16%), chronic pain conditions (346; 14%), osteoporosis (45; 2%), and other (e.g., abnormal labs, 112; 5%). Systemic inflammatory rheumatic disease referrals included inflammatory arthritis (287; 38%), connective tissue diseases and other systemic autoimmune rheumatic diseases (e.g., lupus, scleroderma, Sjogren’s, Raynaud’s) (131; 18%), gout/crystal arthropathies (122; 16%), spondyloarthropathies (120; 16%), polymyalgia rheumatica (66; 9%), and vasculitis (19; 3%). Among systemic inflammatory rheumatic disease patients, time from presentation in primary care to referral exceeded 100 days, except for patients with vasculitis. During this time, 61% of systemic inflammatory rheumatic disease patients received treatment by their family doctor (48% received NSAIDs/COXIBs, and 20% received corticosteroids). For rheumatoid arthritis patients, 72% received treatment (53% received NSAIDs/COXIBs, 27% received corticosteroids, and 6% received DMARDs) prior to rheumatologist consultation; 65% of RA patients were prescribed DMARDs within 4 weeks of the first rheumatology consultation. 33% of systemic inflammatory patients were also seen by another specialist (orthopedic surgeon, internist, allied health professional) for their complaint prior to seeing a rheumatologist.  
Conclusion: We present novel data on the care management of patients with rheumatic diseases from primary care management up until rheumatology consultation. Approximately one in three referrals to rheumatologists were for a systemic inflammatory rheumatic disease. Understanding the referral patterns of family physicians can identify opportunities to improve care management of patients prior to rheumatology referral.
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Contributions of Social Determinants of Health on Remission in Rheumatoid Arthritis Patients
Kangping Cui (University of Toronto, Toronto); George Tomlinson ( University of Toronto, Departments of Health Policy, Management, and Evaluation, and Medicine, Department of Medicine, Toronto); Claire Bombardier (University of Toronto, Toronto); OBRI Ontario Best Practices Research Initiative (Toronto)
Objectives: Treatment responses vary among rheumatoid arthritis (RA) patients. There is limited evidence on the contribution of social determinants of health (SDH) to treatment responses and disease outcomes in RA. This study aimed to determine the contribution of social determinants of health (SDH) to remission in RA.  
Methods: Data were collected from the Ontario Best-practices Research Initiative (OBRI) Rheumatoid Arthritis Registry, a clinical registry of early and established adult RA patients followed in routine care. Treatment response at 6 and 12 months was assessed by the 2011 ACR/EULAR Simple Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) remission criteria. The SDH assessed include patient demographics, socioeconomic status, health behaviors, living condition, marital status, and depression. Variables with a p<0.2 in univariate analyses were included for multivariable regression. The association between SDH and remission was evaluated by logistic regression, controlling for baseline clinical RA confounders such as RA duration and baseline RA medications, presence of X-ray erosion, antibody status, extra articular features, baseline disease activities, and functional disability. All statistical analyses were performed in SAS9.4.  
Results: Among 2209 patients with baseline CDAI, 1832 and 1583 reached the 6- and 12-month follow-up, respectively. Among 1778 patients with baseline SDAI, 1505 and 1286 reached the 6- and 12-month follow-up. At 6 months, 14.8% and 15.5% of the patients achieved CDAI and SDAI remission, respectively. At 12 months, 18.9% and 19.8% of the patients achieved CDAI and SDAI remission. After adjusting for clinical confounders, higher neighborhood income was associated with 6-month CDAI remission (OR 1.04 per $10,000; 95%CI 1.00-1.07), while having private insurance was associated with 6-month SDAI remission (OR 0.63 95%CI 0.40-0.99 for non-insurer). At 12 months, smoking and not living alone were both associated with CDAI and SDAI remission (CDAI: OR 0.65 95%CI 0.44-0.96 for non-smoker, OR 3.02 95%CI 1.27-7.15 for not living alone; SDAI: OR 0.62 95%CI 0.40-0.96 for non-smoker, OR 2.87 95%CI 1.11-7.40 for not living alone). Living in a rural community was also associated with SDAI remission at 12 months (OR 1.79 95%CI 1.12-2.86).  
Conclusion: Socioeconomic factors appear to have an effect on remission at 6 months. Health behavior and living environment appear to be associated with remission at 12 months. Different SDH may affect treatment response and disease outcome at different time points and this study highlights the complexity in studying SDH.     
15
Predictors of Disease Relapse and Recapture of Remission Following Relapse in an Ontario Rheumatoid Arthritis Population
Bindee Kuriya (University of Toronto, Toronto); Xiuying Li (Toronto General Hospital, University Health Network, Toronto); George Tomlinson ( University of Toronto, Departments of Health Policy, Management, and Evaluation, and Medicine, Department of Medicine, Toronto); Ed Keystone (Mount Sinai Hospital, University of Toronto, Toronto); Claire Bombardier (University of Toronto, Toronto)
Objectives: The timing and severity of relapse and likelihood of “recapturing” remission following a relapse in RA is not well known. We aimed to describe time-to-relapse, factors associated with relapse and subsequent remission after relapse. 
Methods: We performed a longitudinal analysis of patients enrolled in the Ontario Best Practices Research Initiative (OBRI), a clinical registry of RA patients in routine care.  First clinical remission according to DAS28-ESR <2.6 following cohort entry was determined. Patients achieving remission with ≥ 1 follow-up visit were observed for average time until relapse (DAS28 >2.6).  Disease activity at relapse as well as the prevalence and timing of subsequent remission was examined. Cox proportional hazards models calculated the hazard of remission and relapse adjusted for baseline variables and time-varying disease activity and medication changes.
Results: Results: The total cohort (N=2591) was 78% female with mean age 57 (13) years. Remission was achieved in 1258 patients (60%) with median time-to-first-remission of 314 days (IQR 153,552). Early RA was the only positive predictor of remission (Table). Among the remission group, 1117 had follow-up and 776 (69%) went on to experience a relapse. Median time-to-relapse was 204 days (IQR 129-390) and the majority switched from a state of remission to mild or moderate disease activity, in contrast to moderate or severe levels of disease activity they experienced at baseline. Variables associated with relapse included female sex, higher DAS28 preceding relapse and use of biologic DMARD (bioDMARD) monotherapy and/or corticosteroids in the interval between remission and relapse; combination conventional synthetic DMARD (csDMARD) appeared to protect against the risk of relapse (Table). 452 (58%) patients regained remission after spending a median of 209 days (IQR 126-386) in a state of relapse.  Similar variables associated with first remission, including disease duration and receipt of combination csDMARD or bioDMARD after relapse, were negatively associated with regaining remission (Table).
Conclusion: Clinical remission in routine care is achievable but relapses to states of low or moderate disease activity are common and may last several months. High disease activity and surrogates of active disease, such as need for biologics or corticosteroids, may predict those at high risk for relapse and justify close monitoring and potentially therapeutic intervention. Recapturing remission after a relapse appears possible but this target occurs with lower frequency than initial remission.  Additional investigation about the optimal timing, dosing and sequence of DMARD therapy needed to maintain and recapture remission will inform how to manage and disease flares.
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What is the Rate of Primary and Secondary Failure of Anti-TNF in RA Patients? Data from a Rheumatoid Arthritis Cohort
Ed Keystone (Mount Sinai Hospital, University of Toronto, Toronto); Mohammad Movahedi (UHN-OBRI, Toronto); Angela Cesta (University Health Network, Toronto); Xiuying Li (Toronto General Hospital, University Health Network, Toronto); Sandra Couto (University Health Network, Toronto); Emmanouil Rampakakis (JSS Medical Research, Montreal); John Sampalis (JSS Medical Research Inc, Montreal); Claire Bombardier (University of Toronto, Toronto)
Objectives: Although most RA patients respond to anti-TNF treatment, some present with refractory disease (primary failure) while others show some initial clinical response and eventually lose responsiveness (secondary failure). Assessing primary/secondary failure is complex due to the use of different definitions and variations in the timing of patient assessment in real-life.   
Methods: Patients from the Ontario Best Practices Research Initiative (OBRI) initiating anti-TNF treatment <30 days prior to or at any point post-OBRI enrolment were included. Those discontinuing anti-TNF due to primary failure or secondary failure, as per the judgment of the treating physician, were re-classified based on: (i) time of failure (<6 months, 6-12 months, >12 months); (ii) prior achievement of DAS28 low disease activity (LDA) or moderate/good EULAR response. Interruptions of <6 months, where patients restarted the same anti-TNF were counted as continuous drug use. Time to treatment discontinuation was assessed with Kaplan-Meier survival analysis.  


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