Canadian Early Arthritis Cohort Research Articles

Risk factors for prevalent and incident hypertension in rheumatoid arthritis: data from the Canadian Early Arthritis Cohort.

Hypertension (HTN) is a common comorbidity in RA. This study aimed to explore the prevalence and incidence of HTN and baseline factors associated with incident HTN in early RA (ERA). Data were from the Canadian Early Arthritis Cohort (CATCH), an inception cohort of ERA patients having <1 year of disease duration. HTN was determined by patient- or physician-reported diagnosis, the use of anti-hypertensives and/or blood pressure. Multivariable logistic regression was performed to determine baseline factors associated with prevalent and incident HTN in this population. The study sample included 2052 ERA patients [mean age 55 years (s.d. 14), 71% female). The prevalence of HTN at study enrolment was 26% (23% in females and 34% in males). In both sexes, prevalent HTN was associated with older age, diabetes and hyperlipidaemia. HTN was associated with being overweight or high alcohol consumption in females. Of the RA patients who did not have HTN at enrolment, 24% (364/1518) developed HTN during the median follow-up period of 5 years (range 1-8). Baseline factors significantly associated with incident HTN were older age, being overweight, excess alcohol consumption and having hyperlipidaemia. Incident HTN was associated with high alcohol consumption in males and with hyperlipidaemia in females. RA-associated disease factors and treatments were not significantly associated with prevalent or incident HTN. Early RA patients had a high incidence of hypertension with the highest risk in older patients with traditional cardiovascular risk factors.

Having More Tender Than Swollen Joints Is Associated With Worse Patient-Reported Outcomes in Patients With Early RA.

In patients with rheumatoid arthritis (RA), high tender-swollen joint differences (TSJDs) have been associated with worse outcomes. A better understanding of the phenotype and impact of high TSJD on patient-reported outcomes (PROs) in early RA may lead to earlier personalized treatment targeting domains that are important to patients today. Our objectives were to evaluate the impact of TSJD on updated PROs in patients with early RA over 1 year and to determine differences in associations by joint size. This longitudinal cohort study followed patients with active, early RA enrolled in the Canadian Early Arthritis Cohort between 2016 and 2022, who completed clinical assessments and PROMIS-29 measures over 1 year. Twenty-eight joint counts were performed and TSJDs calculated. Adjusted associations between TSJD and PROMIS-29 scores were estimated using separate linear-mixed models. Separate analyses of large versus small-joint TJSDs were performed. Patients with early RA (n = 547; 70% female; mean [SD] age, 56 [15] years; mean [SD] symptom duration, 5.3 [2.9] months) were evaluated. A 1-point increase in TSJD was significantly associated with worse PROMIS T-scores in all domains: physical function (adjusted regression coefficient, -0.27; 95% confidence interval [CI], -0.39, -0.15), social participation (adjusted regression coefficient, -0.34; 95% CI, -0.50, -0.19), pain interference (adjusted regression coefficient, 0.49; 95% CI, 0.35, 0.64), sleep problems (adjusted regression coefficient, 0.29; 95% CI, 0.16, 0.43), fatigue (adjusted regression coefficient, 0.34; 95% CI, 0.18, 0.50), anxiety (adjusted regression coefficient, 0.23; 95% CI, 0.08, 0.38), and depression (adjusted regression coefficient, 0.20; 95% CI, 0.06, 0.35). Large-joint TSJD was associated with markedly worse PROs compared with small-joint TSJD. Elevated TSJD is associated with worse PROs particularly pain interference, social participation, and fatigue. Patients with more tender than swollen joints, especially large joints, may benefit from earlier, targeted therapeutic interventions.

Having More Tender Than Swollen Joints is Associated With Worse Function and Work Impairment in Patients With Early Rheumatoid Arthritis.

Patients with early rheumatoid arthritis (RA) may present with more tender than swollen joints, which can persist. Elevated tender-swollen joint difference (TSJD) is often challenging, because there may be multiple causes and it may contribute to overestimating disease activity. Little is known about the phenotype and impact of TSJDs on patient function. Our objective was to evaluate the impact of TSJD on functional outcomes in early RA and to see whether associations vary by joint size. Data were from patients with active, early RA (≤12 months) enrolled in the Canadian Early Arthritis Cohort, who completed assessments of general function (Multidimensional Health Assessment Questionnaire [MDHAQ]), upper extremity (UE) function (Quality of Life in Neurological Disorders [Neuro-QoL] UE scale), and work/activity impairment (Work Productivity and Activity Impairment RA) over their first year of follow-up. A total of 28 joint counts were performed. TSJDs were calculated. Adjusted associations between TSJDs and functional outcomes were estimated in separate multivariable linear mixed effects models. Separate analyses were performed for large- versus small-joint TSJD. Patients (N=547) were 70% female, mean age 56 (SD 15) years, mean disease duration 5.3 (SD 2.9) months. At baseline, 287 (52%) had TSJD >0 (43% involved large joints and 34% small joints), decreasing to 32% at 12 months. A one-point increase in TSJD was significantly associated with worse function (MDHAQ: adjusted mean change 0.10, 95% confidence interval [CI] 0.08-0.13; Neuro-QoL UE function T score: adjusted mean change -0.59, 95% CI -0.76 to -0.43; and greater work impairment: adjusted mean change 1.95%, 95% CI 0.85%-3.05%). Higher large-joint TSJDs were associated with the worst functional outcomes. Having more tender than swollen joints is common in early RA and is associated with worse function, most notably when involving large joints. Early identification and targeted intervention strategies may be needed.

"From Where I Stand": using multiple anchors yields different benchmarks for meaningful improvement and worsening in the rheumatoid arthritis flare questionnaire (RA-FQ).

The Rheumatoid Arthritis Flare Questionnaire (RA-FQ) is a patient-reported measure of disease activity in RA. We estimated minimal and meaningful change from the perspective of RA patients, physicians, and using a disease activity index. Data were from 3- to 6-month visits of adults with early RA enrolled in the Canadian Early Arthritis Cohort. Participants completed the RA-FQ, the Patient Global Assessment of RA, and the Patient Global Change Impression at consecutive visits. Rheumatologists recorded joint counts and MD Global. Clinical Disease Activity Index (CDAI) scores were computed. We compared mean RA-FQ change across categories using patients, physicians, and CDAI anchors. The 808 adults were mostly white (84%) women (71%) with a mean age of 55 and moderate-high disease activity (85%) at enrollment. At V2, 79% of patients classified their RA as changed; 59% were better and 20% were worse. Patients reporting they were a lot worse had a mean RA-FQ increase of 8.9 points, whereas those who were a lot better had a -6.0 decrease. Minimal worsening and improvement were associated with a mean 4.7 and -1.8 change in RA-FQ, respectively, while patients rating their RA unchanged had stable scores. Physician and CDAI classified more patients as worse than patients, and minimal and meaningful RA-FQ thresholds differed by group. Thresholds to identify meaningful change vary by anchor used. These data offer new evidence demonstrating robust psychometric properties of the RA-FQ and offer guidance about improvement or worsening, supporting its use in RA care, research, and decision-making.

Predictors of Influenza Vaccination in Early Rheumatoid Arthritis 2017-2021: Results From the Canadian Early Arthritis Cohort.

ObjectiveAdults with rheumatoid arthritis (RA) are at a higher risk for infections, including influenza and related complications. We identified influenza vaccination coverage in adults newly diagnosed with RA and examined sociodemographic RA characteristics and attitudes associated with vaccination.MethodsWe used data from patients enrolled in the Canadian Early Arthritis Cohort between September 2017 and February 2021. At enrollment, participants reported their vaccination status in the previous year and completed the Beliefs About Medicines Questionnaire (BMQ). Clinical data were obtained from medical records. Logistic regression was used to identify predictors of vaccination in the year after RA diagnosis.ResultsThe baseline analytic sample of 431 patients were mostly White (80%) women (67%) with a mean age of 56 (SD 14) years. Prediagnosis, influenza vaccine coverage was 38%, increasing to 46% post diagnosis in the longitudinal sample (n = 229). Participants with previous influenza vaccination (odds ratio [OR] 15.33; 95% confidence interval [CI] 6.37‐36.90), on biologics or JAKs (OR 5.42; 95% CI 1.72‐17.03), and with a higher change in BMQ Necessity‐Concerns Differential scores (OR 1.08; 95% CI 1.02‐1.15) had greater odds, whereas women (OR 0.32; 95% CI 0.14‐0.71), participants with a non‐White racial background (OR 0.13; 95% CI 0.04‐0.51), and participants currently smoking (OR 0.09; 95% CI 0.02‐0.37) had lower odds of influenza vaccine coverage.ConclusionInfluenza vaccination coverage in patients with early RA remains below national targets in adults living with a chronic condition. Discussing vaccine history and medication attitudes at initial clinic visits with new patients with RA may enhance vaccine acceptance and uptake.

Abstract P030: Traditional Cardiovascular Risk Factors Are Associated With Being Hypertensive At Rheumatoid Arthritis Diagnosis: Results From The Canadian Early Arthritis Cohort

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease causing chronic inflammation of the joints. RA patients have increased risk of hypertension (HTN). The aim of this study was to determine prevalence of HTN at RA diagnosis as well as demographic, behavioral, and clinical characteristics associated with HTN. Hypothesis: We assessed the hypothesis that a large proportion of RA patients are hypertensive at RA diagnosis and that worse disease activity is associated with HTN. Methods: Data from the Canadian Early Arthritis Cohort was used. This is an inception cohort of RA patients across Canada. Data on HTN was collected according to patient/physician-report or use of anti-hypertensive drugs. Prevalence of HTN was calculated. A multivariate logistic regression model was built using likelihood ratio test for the total sample and while stratifying by sex, including variables on age, race, BMI, education, smoking, alcohol, disease activity and comorbidities. Results: The sample included 2052 RA patients. Mean(±SD) for age was 55(14) years and RA symptom duration 5.6(2.9) months, 71% (1438 of 2028) were female and 85% (1709 of 2010) were Caucasian. HTN was reported in 26% (537 of 2052) of subjects, 23% (327 of 1438) of females and 35% (205 of 590) of men. All results of logistic regression are in table 1. In multivariable analysis for the total sample, older age, overweight and obese BMI, diabetes and hyperlipidemia were associated with HTN. For females, excess alcohol consumption was also associated with HTN. In males, only older age, diabetes and hyperlipidemia were associated with HTN. Conclusions: One in four RA patients were hypertensive at RA diagnosis. Traditional risk factors that have been found in the general population were also associated with HTN in RA patients at diagnosis. Whether other characteristics are associated with HTN later in the RA disease course will be explored in further analysis.

A Bridge Too Far? Real-World Practice Patterns of Early Glucocorticoid Use in the Canadian Early Arthritis Cohort.

ObjectiveTo describe patterns of glucocorticoid use in a large real‐world cohort with early rheumatoid arthritis (RA) and assess the impact on disease activity and treatment.MethodsData are from adults with new RA (≤1 year) recruited to the Canadian Early Arthritis Cohort (CATCH) and are stratified on the basis of whether a person was prescribed oral glucocorticoids within 3 months of study entry. Disease activity was compared over 24 months. Mixed‐effects logistic regression was used for adjusted odds ratios (aORs) of escalation to biologics separately for 12 and 24 months, with random effects terms to account for prescribing patterns clustering by study site.ResultsAmong 1891 persons, 30% received oral steroids. Users were older, were less often employed, and had shorter disease duration and higher disease activity. Disease activity improved over time, with early glucocorticoid users starting at higher levels of disease activity. Participants with early oral glucocorticoids were more likely to be on a biologic at 12 months (aOR = 2.4; 95% confidence interval [CI], 1.5‐3.7) and 24 months (aOR = 1.9; 95% CI, 1.3‐3.0). Despite Canadian clinical practice guidelines to limit corticosteroid use to short‐term or ‘bridge’ therapy, 30% of patients who used oral glucocorticoids still used them 2 years later.ConclusionEarly steroids were prescribed sparingly in CATCH and were often indicative of more active baseline disease as well as the need for progression to biologics.

Heterogeneity in Patient Characteristics and Differences in Treatment Across 4 Canadian Rheumatoid Arthritis Cohorts.

To compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts. The 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. In 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%). Canadian 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.

POS1459-HPR IDENTIFYING MEANINGFUL CHANGE IN THE RA FLARE QUESTIONNAIRE SCORES IN RHEUMATOID ARTHRITIS

Background:The RA-FQ is a patient-reported measure of current disease activity in RA that can be used to identify disease flares. The RA-FQ queries pain, physical function, fatigue, stiffness, and participation and yields a score from 0-50. We previously reported on reliability, validity, and responsiveness.Objectives:To identify changes in RA-FQ that represent minimal and meaningful improvement or worsening from the perspective of people with RA, treating rheumatologists, and in relation to disease activity indices. We hypothesized thatMethods:Data were from adults with early RA (sx &lt;1 year) enrolled in the Canadian Early Arthritis Cohort, a prospective study of real-world patients treated across Canada. Participants completed the RA-FQ, Patient Global, and RA transition item since last visit (a little vs. a lot better or worse or same) between consecutive 3- and 6-month visits. Rheumatologists recorded joint counts, MD Global, and change in RA. We compared mean change across improvement and worsening using patient anchors and disease activity indicators.Results:The 808 adults were mostly white (84%) women (71%) with a mean (SD) age of 55 (15) and moderate-high CDAI level (85%) at enrollment. Most (79%) reported their RA had changed; 59% were better and 20% worse. Patients who were a lot worse had a mean increase of 8.9 points whereas those who rated themselves as a lot better had a -6.0 decrease on the RA-FQ (Figure 1). Minimal worsening and improvement were associated with 4.7 and -1.8 change in RA-FQ scores, respectively, while patients who rated their RA unchanged had stable RA-FQ scores (Table 1).Similar changes were evident in CDAI, SDAI, and DAS indices (Table 1). Larger differences were observed with patient vs. physician global scores and tender vs. swollen joints. Across measures, the change associated with worsening was greater than for improvement. Results supported all prespecified hypotheses ab.Table 1.Spearman’s correlation coefficients of PsAQoL with the other parameters for construct validityDomainA Lot Better(N=346; 43%)A Little Better(N=132; 16%)The Same(N=174; 21%)A Little Worse(N=94; 12%)A Lot Worse(N=62; 8%)Δ95% CISDΔ95% CISDΔ95% CISDΔ95% CISDΔ95% CISDRA-FQ Total (0-50)-6.0(-7.1, -4.9)10.3-1.8(-3.2, -0.3)8.4-0.1(-1.3, 1.1)8.14.7(2.9, 6.6)9.18.9(5.1, 12.7)15.0 Pain-1.2(-1.4, -0.9)2.4-0.4(-0.8, 0.0)2.30.0(-0.2, 0.3)1.81.3(0.8, 1.7)2.22.0(1.2, 2.9)3.3 Physical Function-1.3(-1.6, -1.1)2.4-0.3(-0.6, 0.1)2.10.0(-0.3, 0.3)2.10.9(0.4, 1.4)2.41.8(0.8, 2.7)3.7 Fatigue-1.1(-1.4, -0.8)2.6-0.4(-0.7, 0.0)1.90.0(-0.3, 0.3)2.10.7(0.3, 1.1)2.11.3(0.5, 2.1)3.2 Stiffness-1.1(-1.4, -0.9)2.4-0.4(-0.7, 0.0)2.0-0.1(-0.4, 0.2)2.01.1(0.6, 1.5)2.21.8(1.0, 2.7)3.3 Participation-1.2(-1.5, -1.0)2.5-0.1(-0.5, 0.3)2.1-0.1(-0.4, 0.2)2.20.8(0.4, 1.3)2.22.0(1.1, 2.8)3.4Disease ActivityCDAI*-5.3(-6.3, -4.3)9.1-3.3(-5.4, -1.3)11.5-0.8(-2.0, 0.5)8.11.7(-0.1, 3.5)8.86.8(3.7, 9.8)12.0SDAI-5.6(-6.8, -4.4)9.2-3.5(-6.1, -0.9)12.2-1.9(-3.6, -0.2)8.91.5(-0.7, 3.7)9.24.7(1.0, 8.4)12.2DAS28-CRP-0.7(-0.8, -0.6)1.01-0.5(-0.7, -0.2)1.2-0.2(-0.4, 0.0)1.00.3(0.1, 0.5)1.00.5(0.2, 0.9)1.2Patient Global (0-10)-1.3(-1.5, -1.0)2.7-0.5(-0.9, -0.1)2.1-0.1(-0.4, 0.2)2.11.3(0.8, 1.8)2.42.9(2.1, 3.6)3.1MD Global (0-10)-1.2(-1.4, -1.0)1.9-0.7(-1.1, -0.3)-0.1-0.1(-0.4, 0.2)1.90.1(-0.3, 0.5)2.80.7(0.0, 1.5)2.8Swollen Joints (28)-1.4(-1.7, 1.0)3.2-1.0(-1.8, -0.2)4.6-0.4(-0.9, 0.0)3.00.0(-0.7, 0.7)3.41.3(0.2, 2.5)4.6Tender Joints (28)-1.5(-1.9, -1.1)3.9-1.3(-2.2, -0.3)5.50.0(-0.7, 0.6)4.30.3(-0.7, 1.2)4.52.2(0.8, 3.5)5.4Conclusion:In this large cohort of adults with ERA, the RA-FQ was responsive to change and generally distinguish between minimal and meaningful improvement and worsening. These data add to a growing evidence demonstrating robust psychometric properties of the RA-FQ and offer initial guidance about the amount of change associated with improvement or worsening, supporting its use in RA care, research and decision-making.Acknowledgements:The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation and Hoffmann-LaRoche since 2011; Medexus Inc. since 2013;, Merck Canada since 2017, Sandoz Canada, Biopharmaceuticals since 2019,Gilead Sciences Canada since 2020 and Fresenius Kabi Canada Ltd. since 2021. Previously funded by Janssen Biotech from 2011-2016, UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, Sanofi Genzyme from 2016-2017, and Eli Lilly Canada from 2016-2020.Disclosure of Interests:None declared

OP0262-HPR THE NEURO-QOL UPPER EXTREMITY FUNCTION SCALE: NEW OPPORTUNITIES TO MORE RELIABLY AND PRECISELY MEASURE SELF-REPORTED HAND FUNCTION AND SELF-CARE ACTIVITIES IN PEOPLE WITH RA

Background:RA is an inflammatory disease that results in pain and loss of function, especially in the hands and wrists. Brief self-assessment tools that can reliably and precisely quantify hand/wrist function are needed to assess inflammatory activity when a physical exam is not feasible and to capture day-to-day experience of living with RA. Neuro-QoL is part of the PROMIS family of self-report measures created using a patient-centred approach and IRT methodology. The Neuro-Qol Upper Extremity Function (UEF) scale measures ability across fine motor and ADLs involving digital, manual and reach-related function and self-care. Little is known about its performance in RA.Objectives:To evaluate the validity and responsiveness of the 8-item Neuro-QoL UEF in RA. We hypothesized scores would be strongly (r&gt;.70) associated with MHAQ, MD-HAQ, and PROMIS PF, moderately (r=.4 to .7) to symptoms, disease activity, and QoL indicators, and be responsive to change in disease activity and PF.Methods:Data were from the 0 and 6-month visits of adults with early RA (sx &lt;1 yr) enrolled in the Canadian Early Arthritis Cohort, a prospective real-world study at 16 sites across Canada. Participants completed the Neuro-QoL UEF, MHAQ, MDHAQ, PROMIS-29, and PT Global at each visit. Rheumatologists recorded joint counts and MD Global. To evaluate content validity, we examined descriptive statistics across CDAI disease activity levels, and Pearson correlations between the Neuro-QOL UEF, legacy measures, CRP &amp; ESR. Responsiveness was assessed by correlating change scores from visits 0-6 between Neuro-QoL UEF, disease activity and legacy PF scores.Results:The 262 participants were mostly white (83%) women (71%) with a mean (SD) age of 55 (13). Summary statistics at 6-months are shown in Table 1. Neuro-QOL UEF was moderately-strongly correlated with MHAQ, MDHAQ, PROMIS-PF (|r|=.63-.75) and moderately correlated with pain and stiffness, (|r|=.59, -.64), and CDAI, SDAI, PT&amp;MD Global, TJ &amp; SJ (|r|=.39-.58). Neuro-QOL UEF was moderately correlated with PROMIS QoL domains Pain, Fatigue, Anxiety, Depression, Sleep &amp; Participation (|r|=.39-.60).Table 1.Summary statistics of physical function and RA disease activity indices at 6 months.MeanSDMdn25%75%(Min, Max)Physical FunctionNeuro-Qol UEF46.59.753.837.553.8(21.8, 53.8)MHAQ (0-3)0.290.430.130.000.38(0.00, 2.25)MD-HAQ (0-10)1.391.640.700.002.00(0.00, 8.00)PROMIS-PF46.48.546.239.556.0(23.3, 56.0)RA Disease ActivityCDAI9.39.96.03.013.0(0.0, 56.0)SDAI10.710.96.83.115.2(0.0, 57.0)Patient Global3.02.5315(0, 10)MD Global1.82.2103(0, 9)Swollen Joints (28)2.13.7002(0, 20)Tender Joints (28)2.43.9103(0, 24)Neuro-QOL scores decreased in a dose-response manner across worsening CDAI DA states reflecting increasing impairment (Table 2). Persons with HDA reported the highest disability, scoring nearly 0.5 SD lower on the Neuro-QoL UEF than PROMIS PF. Change from baseline to 6 months in Neuro-QoL UEF was moderately correlated with changes in PROMIS PF, MHAQ, PT Global, and CDAI (|r|=.44-.65). The mean change and range from 0-6 months in Neuro-QoL was significantly larger than in PROMIS (8.9 [95% CI 7.5, 10.4] vs. 5.4 [95% CI 4.4, 6.4])(see Figure).Table 2.Mean scores (95% CI) at 6 months by CDAI level.REMLDAMDAHADNeuroQol UEF52.8 (51.8, 53.7)48.1 (46.6, 49.7)42.0 (39.4, 44.6)33.8 (30.5, 37.1)MHAQ (0-3)0.05 (0.02, 0.09)0.19 (0.14, 0.24)0.45 (0.34, 0.57)0.90 (0.63, 1.17)MD-HAQ (0-10)0.31 (0.17, 0.46)1.11 (0.90, 1.32)2.15 (1.71, 2.59)3.56 (2.56, 4.56)PROMIS-PF52.8 (51.4, 54.2)46.8 (45.3, 48.2)42.3 (40.4, 44.2)38.0 (34.4, 41.6)Conclusion:Clinicians, researchers, and patients benefit from practical self-report tools that reliably and precisely monitor hand function in RA. Results offer initial evidence of validity and responsiveness and support use of Neuro-QoL UEF to self-assess inflammatory activity in the hands and day-to-day experiences of living with RA.Acknowledgements:The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation and Hoffmann-LaRoche since 2011; Medexus Inc. since 2013;, Merck Canada since 2017, Sandoz Canada, Biopharmaceuticals since 2019,Gilead Sciences Canada since 2020 and Fresenius Kabi Canada Ltd. since 2021. Previously funded by Janssen Biotech from 2011-2016, UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, Sanofi Genzyme from 2016-2017, and Eli Lilly Canada from 2016-2020.Disclosure of Interests:None declared

Health Assessment Questionnaire at One Year Predicts All-Cause Mortality in Patients With Early Rheumatoid Arthritis.

Higher self-reported disability (high Health Assessment Questionnaire [HAQ] score) has been associated with hospitalizations and mortality in established rheumatoid arthritis (RA), but associations in early RA are unknown. Patients with early RA (symptom duration <1 year) enrolled in the Canadian Early Arthritis Cohort who initiated disease-modifying antirheumatic drugs and had completed HAQ data at baseline and 1 year were included in the study. Discrete-time proportional hazards models were used to estimate crude and multi-adjusted associations of baseline HAQ and HAQ at 1 year with all-cause mortality in each year of follow-up. A total of 1,724 patients with early RA were included. The mean age was 55 years, and 72% were women. Over 10 years, 62 deaths (3.6%) were recorded. Deceased patients had higher HAQ scores at baseline (mean ± SD 1.2 ± 0.7) and at 1 year (0.9 ± 0.7) than living patients (1.0 ± 0.7 and 0.5 ± 0.6, respectively; P < 0.001). Disease Activity Score in 28 joints (DAS28) was higher in deceased versus living patients at baseline (mean ± SD 5.4 ± 1.3 versus 4.9 ± 1.4) and at 1 year (mean ± SD 3.6 ± 1.4 versus 2.8 ± 1.4) (P < 0.001). Older age, male sex, lower education level, smoking, more comorbidities, higher baseline DAS28, and glucocorticoid use were associated with mortality. Contrary to HAQ score at baseline, the association between all-cause mortality and HAQ score at 1 year remained significant even after adjustment for confounders. For baseline HAQ score, the unadjusted hazard ratio (HR) was 1.46 (95% confidence interval [95% CI] 1.02-2.09), and the adjusted HR was 1.25 (95% CI 0.81-1.94). For HAQ score at 1 year, the unadjusted HR was 2.58 (95% CI 1.78-3.72), and the adjusted HR was 1.75 (95% CI 1.10-2.77). Our findings indicate that higher HAQ score and DAS28 at 1 year are significantly associated with all-cause mortality in a large early RA cohort.

Improvements in Fatigue Lag Behind Disease Remission in Early Rheumatoid Arthritis: Results From the Canadian Early Arthritis Cohort.

To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA). Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11-point numerical rating scale (NRS) for up to 5 years of follow-up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3-months of cohort entry were compared. Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56-0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C-reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow-up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow-up. Maximal improvements in fatigue lagged behind remission by 6 months. Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3-months was associated with short-term and long-term benefits in fatigue over time.

THU0179 PERSISTENCE IN RHEUMATOID ARTHRITIS PATIENTS ON BIOSIMILAR AND BIO-ORIGINATOR ETANERCEPT: A POOLED ANALYSIS OF PAN-CANADIAN COHORTS

Background:Biosimilar etanercept (ETA-B) was recently introduced in Canada but real-world data descriptions of drug persistence (and comparisons with the originator product, ETA-O) are still scarce.Objectives:To describe and compare persistence of ETA-B and ETA-O in RA.Methods:We used data from four ongoing, prospective cohorts in Canada: the Canadian Early Arthritis Cohort (CATCH), the Rheumatoid Arthritis Pharmacovigilance Program and Outcomes Research in Therapeutics (RAPPORT), the Early Undifferentiated Polyarthritis (EUPA) cohort, and the RHUMADATA® registry. We studied biologic-naïve and biologic-experienced RA adults initiating ETA-B or ETA-O between Jan. 2015 and Oct. 2019. Switchers from ETA-O to ETA-B (or vice-versa) were included. We assessed persistence of therapy in the first 12 or 24 months, measured as time from therapy initiation (time zero) to discontinuation. Individuals switching between products could contribute further person-time to the new exposure category. Multivariable Cox regression models were performed with each cohort dataset separately, following a common protocol. Model variables included age, sex, comorbidity, past biologic use, and disease duration. After testing for between-study heterogeneity (Higgin’s I2), cohort-estimated hazard ratios (HR) were pooled using random effects meta-analysis.Results:We identified 262 episodes of etanercept use (118 ETA-B and 144 ETA-O) from 250 RA patients. Sex, age, and other baseline characteristics across the four cohorts are shown in Table 1. Across cohorts, there was considerable variation in RA duration at the time of initiating ETA-B or ETA-O. In the pooled analysis, the HR for discontinuation at 24 months comparing ETA-B to ETA-O was 0.51 (95% confidence interval, CI: 0.26-0.98). The pooled analysis for therapy discontinuation at 12 months adjusted HR in this analysis was 0.82 (95% CI: 0.42-1.60).Table 1.Characteristics of studied patients according to their treatment episodes, biosimilar etanercept (ETA-B) or bio-originator etanercept (ETA-O).CharacteristicEUPARAPPORTRHUMADATACATCHETA-BETA-OETA-BETA-OETA-BETA-OETA-BETA-ON=19N=27N=32N=30N=39N=52N=28N=35Female sex, (%)12 (63)18 (67)20 (63)22 (73)28 (72)38 (73)20 (71)27 (77)Mean age in years1, SD59 (13)59 (16)51 (15)54 (15)59 (15)54 (15)55 (12)51 (13)Current smoker, (%)3 (17)5 (21)9 (32)5 (19)8 (21)9 (17)5 (18)8 (23)Cardiovascular disease, (%)0 (0)0 (0)1 (3.1)1 (3.3)8 (21)2 (4)NANADiabetes, (%)0 (0)0 (0)4 (13)1 (3)2 (5)3 (6)NANAHypertension, (%)NANA5 (16)4 (13)14 (36)22 (42)NANARA duration in years1, SD2 (3)7 (13)8 (6)12 (15)12 (12)9 (9)4 (4)3 (3)DAS-2812 (NA)4 (2.8)6 (1)6 (1)4 (2)4 (1)4.0 (2)4 (2)SDAI113 (14)44 (5)NANA21 (15)23 (8)23 (14)25 (16)Past oral steroids, N(%)Past biologic, N(%)15 (79)17 (63)6 (19)4 (13)29 (74)31 (60)9 (32)13 (37)Past non-biologic DMARD,8 (42)6 (22)2 (6)0 (0)21 (54)20 (38)19 (68)21 (60)N(%)19 (100)27 (100)30 (94)26 (87)39 (100)52(100)25 (89)33 (94)1At time zero or at the closest date before time zero. SD=standard deviationConclusion:Despite wide confidence intervals, the 24-month data suggested potential better persistence with ETA-B versus ETA-O, with a similar trend at 12 months. Some of the observed associations may be related to residual confounding (e.g. disease activity, time-dependent effects of concomitant medications) and/or survivorship bias (in patients transitioning from ETA-O to ETA-B).Disclosure of Interests:Cristiano S Moura: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Coupal: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Vivian Bykerk: None declared, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB., Sasha Bernatsky: None declared

A quarter of patients time their early rheumatoid arthritis onset differently than physicians

ObjectiveEarly rheumatoid arthritis (RA) treatment requires timely recognition. This large, multicentre study compared patient-reported vs physician-reported onset of early RA.MethodsPatients from the Canadian Early ArThritis CoHort with early/suspected RA (persistent...

Palindromic Rheumatism Frequently Precedes Early Rheumatoid Arthritis: Results From an Incident Cohort.

BackgroundThis multicenter incident cohort aimed to characterize how often early rheumatoid arthritis (ERA) patients self‐report episodic joint inflammation (palindromic rheumatism) preceding ERA diagnosis and which characteristics differentiate these patients from those without prior episodic symptoms.MethodsData were from patients with early confirmed or suspected RA (more than 6 weeks and less than 12 months) enrolled in the Canadian Early ArThritis CoHort (CATCH) between April 2017 to March 2018 who completed study case report forms assessing joint pain and swelling prior to ERA diagnosis. Chi‐square and t tests were used to compare characteristics of patients with and without self‐reported episodic joint inflammation prior to ERA diagnosis. Multivariable logistic regression was used to identify sociodemographic and clinical measures associated with past episodic joint inflammation around the time of ERA diagnosis.ResultsA total of 154 ERA patients were included; 66% were female, and mean (SD) age and RA symptom duration were 54 (15) years and 141 (118) days. Sixty‐five (42%) ERA patients reported a history of episodic joint pain and swelling, half of whom reported that these symptoms preceded ERA diagnosis by over 6 months. ERA patients with past episodic joint inflammation were more often female, had higher income, were seropositive, had more comorbidities, fewer swollen joints, and lower Clinical Disease Activity Index (CDAI) around the time of ERA diagnosis (P < 0.05). These associations remained significant in multivariable regression adjusting for other sociodemographic and RA clinical measures.ConclusionAlmost half of ERA patients experienced episodic joint inflammation prior to ERA diagnosis. These patients were more often female, had higher income, and presented with milder disease activity at ERA diagnosis.

Prevalence and Characteristics of Metabolic Syndrome Differ in Men and Women with Early Rheumatoid Arthritis.

ObjectiveMetabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA.MethodsA cross‐sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex‐stratified logistic regression identified baseline variables associated with MetS.ResultsThe sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high‐density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures.ConclusionThe characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

Association of Arthritis Onset with Influenza: Analysis of the Canadian Early Inflammatory Arthritis Cohort.

ObjectiveTo evaluate seasonal patterns of early inflammatory arthritis (IA) onset and potential associations with IA symptom onset.MethodsThe Canadian Early Arthritis Cohort (CATCH) is an inception cohort study of adults with early (12 months or less) IA. We used patient reports of symptom onset as a proxy of IA onset and examined the seasonal distribution of IA onset over 10 years. Influenza time series was based on laboratory‐confirmed influenza A and B from the Canadian FluWatch surveillance from 2010‐2016. Bivariate analysis of influenza and IA was performed using cross‐correlations with different time lags and Poisson regression. IA and influenza were recorded as monthly total frequencies.ResultsOf 2519 IA patients, 88% had confirmed rheumatoid arthritis (RA). Significantly, more IA onsets occurred in winter compared with other seasons (P = 0.03); although IA onset was more frequent in January, the difference between months was not statistically significant. Compared to months with the lowest influenza rates, months with the highest influenza rates had a statistically significant, but trivial, increase of 0.003% in the incidence of IA (incidence rate ratio (95% confidence interval): 1.00003 (1.00005; 1.000053), P = 0.02).ConclusionAlthough IA symptom onset occurs more frequently in winter, we found that flu outbreaks were not associated with a meaningful increase in IA symptom onset in a large, well‐characterized cohort of Canadian adults over 6 years.

Overweight, Obesity, and the Likelihood of Achieving Sustained Remission in Early Rheumatoid Arthritis: Results From a Multicenter Prospective Cohort Study.

Obesity is implicated in rheumatoid arthritis (RA) development, severity, outcomes, and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the 3 years following RA diagnosis. Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of early RA patients treated by rheumatologists using guideline-based care. sREM was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were stratified by body mass index (BMI) as healthy (18.5-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). Cox regression was used to estimate the effect of the BMI category on the probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, Health Assessment Questionnaire disability index, C-reactive protein level, and initial treatment. Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75 [95% confidence interval (95% CI) 0.58-0.98]) and obese patients (HR 0.53 [95% CI 0.39-0.71]) were significantly less likely to achieve sREM. Rates of overweight and obesity were high (69%) in this early RA cohort. Overweight patients were 25% less likely, and obese patients were 47% less likely, to achieve sREM in the first 3 years, despite similar initial disease-modifying antirheumatic drug treatment and subsequent biologic use. This is the largest study demonstrating the negative impact of excess weight on RA disease activity and supports a call to action to better identify and address this risk in RA patients.

High Adherence to System-Level Performance Measures for Rheumatoid Arthritis in a National Early Arthritis Cohort Over Eight Years.

ObjectiveTo assess adherence to 3 system‐level performance measures in a national early rheumatoid arthritis (RA) cohort.MethodsPatients enrolled in the Canadian Early Arthritis Cohort (2007–2015) who met 1987 or 2010 American College of Rheumatology/European League Against Rheumatism criteria with <1 year of symptom duration and ≥1 year of followup after enrollment were included. Performance measures assessed were the percentage of RA patients seen in yearly followup, and the number of gaps between visits of >12 or >14 months, the percentage of RA patients treated with a disease‐modifying antirheumatic drug (DMARD), and days from RA diagnosis to initiation of a DMARD. Results are shown stratified by enrollment year to assess for temporal changes in performance.ResultsA total of 1,763 early RA patients were included (mean age 54 years, 73% female, and 82% white). At enrollment, mean ± SD disease duration was 6 ± 3 months, and Disease Activity Score in 28 joints was 5.1 ± 1.5. Over 8 years, the proportion of patients seen in annual followup declined from 100% to 91%. Over followup, 42% of patients had 0 gaps in care of >12 months, and 64% had 0 gaps >14 months. The percentage of DMARD‐treated early RA patients was and remained high (95–87%), and the percentage receiving DMARDs within 14 days of diagnosis was 75%. Median time‐to‐DMARD therapy was 1 day, indicating DMARDs were initiated at diagnosis (90th percentile 93 days).ConclusionThere was evidence of high adherence to system‐level performance measures in this early RA cohort following a protocol. Small declines in performance were noted with increasing length of patient followup. Our findings are useful for performance measure benchmarking.

Validation of Self-Reported Cardiovascular Disease and Associated Co- Morbidities in a Large Canadian Cohort of Early Inflammatory Arthritis

Objective: Cardiovascular disease (CVD) and risk factors for CVD (smoking, hypertension, dyslipidemia and diabetes) are commonly associated with Rheumatoid Arthritis (RA). We aimed to determine the validity of selfreported CVD events and risk factors in the Canadian Early Arthritis Cohort (CATCH). Methods: CATCH is a multicenter inception cohort of patients with early RA. Various co-morbidities and pharmacologic therapies are self-reported at baseline and at each follow-up visit. Using a randomly selected subgroup of subjects enrolled in CATCH from one representative site, we performed a detailed review of their complete medical record to identify diagnoses of CVD events, risk factors and drug therapies. The validity of selfreported variables was determined using the Cohen’s kappa statistic. Results: The validation subgroup (N=141) was similar to the entire CATCH population (N=2626) with respect to baseline demographics and RA disease characteristics. There was very good agreement between self-report and the medical record for cardiovascular or cerebrovascular events (kappa=0.66), as well as for hypertension and diabetes (kappa=0.70 and 0.81, respectively). Subjects tended to under-report dyslipidemia and the reporting of lipid-lowering and antiplatelet/anticoagulant agents was inaccurate compared to the medical record. Conclusion: Self-reported cardiovascular disease, hypertension and diabetes was representative of the medical record suggesting that these self-reported variables are valuable for future studies of this early RA population.