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

Objective: 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). Methods: 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. Results: 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. Conclusions: 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.

BACKGROUND/OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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).

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

OBJECTIVE: Adults 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: Influenza 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.

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

OBJECTIVE: To 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. METHODS: Data 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. RESULTS: Among 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. CONCLUSION: Early steroids were prescribed sparingly in CATCH and were often indicative of more active baseline disease as well as the need for progression to biologics.

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

OBJECTIVE: To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Treatment Strategies in Early Rheumatoid Arthritis Methotrexate Management: Results From a Prospective Cohort.

OBJECTIVE: To assess real-world practice patterns surrounding treatment initiation and adjustments over time for methotrexate (MTX) and non-MTX-based treatment strategies in early rheumatoid arthritis (RA). METHODS: We studied a multicenter, incident early RA cohort (enrolled 2007-2017 within 1 year of symptoms) who fulfilled American College of Rheumatology/European League Against Rheumatism criteria. Adult patients with RA were eligible if treatment with MTX (± other disease-modifying antirheumatic drugs [DMARDs]) was initiated within 90 days of cohort entry. We compared time until treatment change for 4 initial MTX-based therapies and time to second treatment change after the first change. The definition of treatment change included changing of route for MTX monotherapy, adding or stopping a DMARD or biologic, and changing dose/frequency of a DMARD or biologic. RESULTS: There was great variability of treatment at initiation and during therapy adjustment. In 1,484 patients with early RA, the majority initiated MTX monotherapy (oral or subcutaneous [SC]). Patients receiving SC MTX monotherapy changed treatment less (45% versus 79%) and remained on treatment longer (hazard ratio [HR] 0.52 [95% confidence interval (95% CI) 0.4-0.67]) than those receiving oral MTX monotherapy. Most therapy adjustments involved adding a DMARD or changing to a non-MTX DMARD. Those adults taking biologics and who were receiving triple therapy had a longer time without treatment change (HR 0.26 [95% CI 0.16-0.42] and HR 0.57 [95% CI 0.38-0.85], respectively). CONCLUSION: We found large variability in the way MTX-based therapies are prescribed in clinical practice. Our findings support the use of SC MTX monotherapy or MTX combination as initial therapy. For subsequent treatment after initial MTX-based therapy, those patients initiating either biologics or triple therapy had a longer time to treatment change than oral MTX monotherapy.

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

Objective: Early rheumatoid arthritis (RA) treatment requires timely recognition. This large, multicentre study compared patient-reported vs physician-reported onset of early RA. Methods: Patients from the Canadian Early ArThritis CoHort with early/suspected RA (persistent synovitis <1 year) completed questionnaires asking about the date of symptom onset; and rheumatologists date of onset for persistent synovitis. Groups with similar reported timing (patient and physician) versus differing timing of 30 days or more were compared. Results: In 2683 patients, the median patient symptom duration (IQR) was 178 days (163) and physician-reported duration was 166 (138). 1940 (72%) patients had similar patient-reported and physician-reported onset (<30 days), whereas 497 (18%) reported onset 30 or more days preceding physicians, and 246 (9%) 30 or more days after physicians. Patients reporting onset preceding physicians had lower baseline Disease Activity Score based on 28 joint count, swollen joint counts and erythrocyte sedimentation rate (p<0.05). Patients reporting onset after physicians were more likely to be rheumatoid factor positive (p<0.001) and had higher anticitrullinated protein antibody titres (p<0.009). Regression showed low income, smoking, fibromyalgia, osteoarthritis and baseline non-methotrexate non-biological disease-modifying antirheumatic drug use were predictors for longer patient-reported symptoms. At 12 months, patients reporting longer symptom duration than physicians had lower rates of Simplified Disease Activity Index remission and higher physician global assessments. Conclusion: Over one-fourth of patients reported differences of >1 month in symptom onset from their rheumatologist. Patients with longer symptom durations had less improvement at 1 year, which may be reflective of comorbid musculoskeletal conditions.

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

OBJECTIVE: To evaluate seasonal patterns of early inflammatory arthritis (IA) onset and potential associations with IA symptom onset. METHODS: The 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. RESULTS: Of 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). CONCLUSION: Although 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.

Joint Estimation of Remission and Response for Methotrexate-Based DMARD Options in Rheumatoid Arthritis: A Bivariate Network Meta-Analysis.

OBJECTIVE: To jointly estimate American College of Rheumatology (ACR50) response (a more commonly reported outcome) and remission (a more clinically relevant outcome) for methotrexate (MTX)-based treatment options in rheumatoid arthritis (RA). METHODS: We conducted a bivariate network meta-analysis (NMA) to compare MTX monotherapy and MTX-based conventional and biologic disease-modifying antirheumatic drug (DMARD) combinations for RA. The correlation between the outcomes was derived from an incident RA cohort study, whereas the treatment effects were derived from randomized trials in the network of evidence. The analyses were conducted separately for MTX-naïve and MTX-inadequate response (IR) populations in a Bayesian framework with uninformative priors. RESULTS: From the cohort study, the correlation between ACR50 response and Disease Activity Score 28 remission at 6 months was moderate (Pearson correlation coefficient = 0.58). In the bivariate NMA for MTX-naïve populations, most combinations of MTX with either biologic or tofacitinib were statistically superior to MTX alone for both ACR50 response and remission. Triple therapy (MTX + sulfasalazine + hydroxychloroquine) was the only nonbiologic DMARD statistically superior to MTX for either ACR50 response (odds ratio [OR] 95% credible interval: 2.1 [1.0, 4.3]) or remission (OR: 2.5 [1.0, 5.8]). In the MTX-IR analysis, all treatments except MTX + sulfasalazine were statistically superior to MTX alone. Compared to analyzing the outcomes separately, the bivariate model often resulted in more precise estimates and allowed remission to be estimated for all treatments. CONCLUSION: Borrowing the strength of correlation between outcomes allowed us to demonstrate a statistically significant benefit for remission across most MTX-based DMARD combinations, including triple therapy.

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

OBJECTIVE: To assess adherence to 3 system-level performance measures in a national early rheumatoid arthritis (RA) cohort. METHODS: Patients 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. RESULTS: A 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). CONCLUSION: There 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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Early Rheumatoid Arthritis Presentation, Treatment, and Outcomes in Aboriginal Patients in Canada: A Canadian Early Arthritis Cohort Study Analysis.

OBJECTIVE: Health inequities exist in chronic diseases for Aboriginal people. This study compared early rheumatoid arthritis (RA) presentation, treatment, and outcomes between Aboriginal and white patients in a large Canadian cohort study. METHODS: Longitudinal data from the Canadian Early Arthritis Cohort, a prospective multicenter early RA study, were analyzed for participants who self-identified as Aboriginal or white ethnicity. Disease characteristics at presentation, prognostic factors, frequency of remission, and disease-modifying therapy strategies were contrasted between population groups. Linear mixed models were used to estimate rates of change for disease activity measures over a 5-year period. RESULTS: At baseline, 2,173 participants (100 Aboriginal and 2,073 white) had similar mean ± SD symptom duration (179 ± 91 days), 28-joint Disease Activity Scores (DAS28; 4.87 ± 1.48), and Health Assessment Questionnaire (0.88 ± 0.68) scores. Factors associated with poor prognosis were more frequently present in Aboriginal participants, but disease-modifying therapy selection and frequency of therapy escalation was similar between the 2 groups. DAS28 remission was achieved less frequently in Aboriginal than in white participants (adjusted odds ratio 0.39 [95% confidence interval 0.25-0.62]). Results were primarily driven by slower improvement in swollen joint counts and nonsignificant improvement in patient global scores in Aboriginal participants. Pain levels remained higher in Aboriginal patients. CONCLUSION: Aboriginal early RA patients experienced worse disease outcomes than their white counterparts. This may reflect unmeasured biologic differences and/or disparities in prognostic factors informed by inequities in determinants of health. The appropriateness of current treatment strategies applied in different contexts should be considered.

Thresholds for the 28-joint disease activity score (DAS28) using C-reactive protein are lower compared to DAS28 using erythrocyte sedimentation rate in early rheumatoid arthritis.

OBJECTIVES: The 28-Joint Disease Activity Score (DAS28) using C-reactive protein (CRP) and DAS28 using erythrocyte sedimentation rate (DAS28-ESR) may not be interchangeable. We sought to compare and estimate optimal thresholds for the DA28-CRP for use in early rheumatoid arthritis (ERA). METHODS: Patients from the Canadian Early Arthritis Cohort with baseline and 12 months' data for both DAS28-ESR and DAS28-CRP were examined for correlations and differences between DAS28-CRP and DAS28-ESR across their range of values. Receiver operating characteristic analysis identified thresholds for DAS28-CRP that best corresponded to established thresholds for the DAS28-ESR using the total sample, then stratified by age and sex. Agreement between DAS28-CRP and DAS28-ESR thresholds was assessed with the kappa statistic. RESULTS: The sample included 995 patients with mean (SD) age of 53.7 (14.5) years, 5.8 (2.9) months of symptom duration and 74% were female. DAS28-CRP and DAS28-ESR scores were highly correlated (r= 0.92, p<0.0001), however DAS28-CRP values were consistently lower than DAS28-ESR values. Calculated thresholds for DAS28-CRP were lower with 2.5 for remission, 2.9 for low disease activity, and 4.6 for high disease activity but showed moderate agreement with the DAS28-ESR thresholds (kappa=0.70). CONCLUSIONS: In this large sample of ERA patients, newly estimated thresholds for DAS28-CRP were consistently lower than DAS28-ESR thresholds across the spectrum of disease activity. This may have important clinical implications if inflammatory markers are used interchangeably. Additional external validation of our findings is needed.

The effect of rheumatoid arthritis-associated autoantibodies on the incidence of cardiovascular events in a large inception cohort of early inflammatory arthritis.

Objective: . RA is associated with an increased risk of cardiovascular events (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with early RA. Methods: Patients were enrolled in the Canadian Early Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular events, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. Results: . A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months ( s . d . 4.6), the mean age was 53 years ( s . d . 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. Conclusion: The rate of CVEs early in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support early aggressive management of RA disease activity and co-morbidities to prevent severe complications.

Predicting Low Disease State and Remission in Early Rheumatoid Arthritis in the First Six Months, Comparing the Simplified Disease Activity Index and European League Against Rheumatism Response Measures: Results From an Early Arthritis Cohort.

OBJECTIVE: To compare the European League Against Rheumatism (EULAR) and Simplified Disease Activity Index 50% (SDAI50) response measures (RMs) and their impact on future response to treatment in patients with early rheumatoid arthritis (ERA). METHODS: Biologic agent-naive ERA patients from the Canadian Early Arthritis Cohort study with complete data at baseline, 3, and 6 months were evaluated. Kappa statistics were used to evaluate the agreement between the EULAR (moderate or good response) and SDAI50 RMs. The RMs at 3 months were also compared for their ability to predict low disease activity state (LDAS) or remission (REM) at 6 months. RESULTS: A total of 1,124 patients were evaluated. Of those, 215 patients (30%) and 294 patients (45%) failed to achieve a EULAR and SDAI50 response, respectively. There was a good agreement between EULAR and SDAI50 RMs with a kappa of 0.59 (95% confidence interval 0.53-0.66). Throughout the range of disease activity, the SDAI50 response was shown to be more stringent than the EULAR response. Multivariable linear regression analysis demonstrated that both RMs at 3 months were associated with LDAS or REM at 6 months, and SDAI50 had a more significant impact on this outcome compared to the EULAR response. CONCLUSION: There is a good agreement between the EULAR and SDAI50 RMs. Although a minority of patients have discordant RMs at each end of the disease activity spectrum at baseline, the SDAI50 response at 3 months appears to be a more significant predictor of outcomes at 6 months than EULAR response.

The rapid kinetics of optimal treatment with subcutaneous methotrexate in early inflammatory arthritis: an observational study.

BACKGROUND: Methotrexate (MTX) is standard treatment for RA. Absorption is better in subcutaneous MTX (scMTX), which may impact speed of onset. In RA, earlier time to remission improves long-term results. Our objectives were to determine rapidity of response of subcutaneous methotrexate in early rheumatoid arthritis. METHODS: The change in several disease activity measures (including DAS28) from 0 to 6 weeks (early period) and 6 to 12 weeks (late period) was compared. The proportion achieving DAS28/CDAI/SDAI remission and/or low disease activity state was also compared. RESULTS: One hundred three patients were included from a single site between 2008 and 2014. All received MTX (98.0 % scMTX, 98 % 25 mg/week). There were no dropouts. There was a significantly greater early change in DAS28 (-1.9 vs. -0.2, p < 0.00); this effect was seen for several outcome measures. By 6 weeks, 59 % had achieved either DAS28 remission or low disease activity state, with 74 % achieving either state by 12 weeks. There were a larger proportion of patients achieving CDAI and DAS28 remission in the early versus late period (p < 0.0002 for both). There was significant improvement when using combination MTX and HCQ, however sample size was small (n = 9). The use of intra-articular steroids with MTX yielded the most disease measures that demonstrated early significant improvement. CONCLUSION: Subcutaneous MTX is rapid, as the change in many disease activity scores was significantly greater between 0-6 weeks compared to 6-12 weeks. Combination MTX + HCQ gave added value, although generalizability is limited by combination cohort sample size. Intra-articular steroid injections may contribute to the early effect.

Treatment preferences of patients with early rheumatoid arthritis: a discrete-choice experiment.

OBJECTIVE: To quantify the preferences of patients with early RA (ERA) with the benefits and harms of DMARDs. METHODS: We assessed patients' preferences using a discrete-choice experiment, an experimentally designed survey to measure trade-offs. Consecutive adult patients with ERA (<2 years since diagnosis) were presented 13 different sets of three treatment options described by eight attributes (clinical outcomes, risks and dosing regimens) and asked to choose one. From patients' responses we estimated the average importance of each attribute and explored preference heterogeneity through latent-class analysis. RESULTS: A total of 152 patients completed the survey (86% response rate): mean age 52 years, 63% female, disease duration 7.8 months. Treatment benefits (increasing the chance of a major symptom improvement and reducing the chance of serious joint damage) were most important. Of potential adverse events, a small risk of serious infections/possible increased risk of cancer was most important. Patients were willing to accept this risk for a 15% absolute increase in the chance of a major symptom improvement. Patients had an aversion to i.v. therapy, but were relatively indifferent to other dosing regimens. Through latent-class analysis, we identified two patient groups: 54% who were more risk averse, particularly to a possible risk of cancer/infection, and others who were highly benefit-driven. CONCLUSION: On average, patients with ERA were risk tolerant, but important differences in preferences were identified. In particular, a subgroup of patients may prefer to avoid treatments with a possible increased risk of cancer/infection if other effective options are available.

Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set.

OBJECTIVE: To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare). RESULTS: The 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16-32% were flaring at the second visit. Agreement of flare status was low-strong (κ's 0.17-0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's≥0.70) with each other, patient global (r's≥0.66) and corresponding measures (r's 0.49-0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29-0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1-3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares.