Canadian Rheumatology Association Living Guidelines for Rheumatoid Arthritis: Update #2.

We have updated the Canadian Rheumatology Association (CRA) guidelines for rheumatoid arthritis (RA) with 3 recommendations for the use of glucocorticoids (GCs). The recommendations address the use of short-term GCs for RA flares or as bridging therapy when disease-modifying antirheumatic drugs (DMARDs) are initiated or changed, and the use of long-term GCs as adjuncts to DMARDs.

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.

Canadian Rheumatology Association Living Guidelines for the Pharmacological Management of Rheumatoid Arthritis With Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: To provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada. METHODS: The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel composed of rheumatologists, researchers, methodologists, and patients. In this first installment of our living guideline, the panel developed a recommendation for the tapering of biologic and targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) therapy in patients in sustained remission using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, including a health equity framework developed for the Canadian RA population. The recommendation was adapted from a living guideline of the Australia & New Zealand Musculoskeletal Clinical Trials Network. RESULTS: In people with RA who are in sustained low disease activity or remission for at least 6 months, we suggest offering stepwise reduction in the dose of b/tsDMARD without discontinuation, in the context of a shared decision, provided patients are able to rapidly access rheumatology care and reestablish their medications if needed. In patients where rapid access to care or reestablishing access to medications is challenging, we conditionally recommend against tapering. A patient decision aid was developed to complement the recommendation. CONCLUSION: This living guideline will provide contemporary RA management recommendations for Canadian practice. New recommendations will be added over time and updated, with the latest recommendation, evidence summaries, and Evidence to Decision summaries available through the CRA website (www.rheum.ca).

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.

Frequency of Symptomatic Adverse Events in Rheumatoid Arthritis: An Exploratory Online Survey.

OBJECTIVE: To generate initial data on the frequency and effect of symptomatic adverse events (AEs) associated with rheumatoid arthritis (RA) drug therapy from the patient perspective. METHODS: We conducted an exploratory online survey asking patients with RA to indicate whether they currently or had ever experienced the 80 different symptomatic AEs included in the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Results were summarized to report their frequency, and regression models were used to estimate their associations with RA medication use and overall bother. RESULTS: The 560 patients who completed the survey and reported taking ≥ 1 RA medication (disease-modifying antirheumatic drugs [DMARDs], steroids, nonsteroidal antiinflammatory drugs [NSAIDs]), had a mean disease duration of 8 years, and were on a wide range of DMARDs. The number of symptomatic AEs experienced in the past 7 days was none (6%), 1-10 (28%), 11-20 (28%), and > 20 (38%). Overall, most participants reported that side effects bothered them somewhat (28%), quite a bit (24%), or very much (15%). In multivariable regression analyses, current prednisone and NSAID use were associated with the greatest number of current side effects (26 and 22, respectively). Many of the strongest associations between current symptomatic AEs and medication use aligned with known side effect profiles. CONCLUSION: In this exploratory online survey, patients with RA reported frequent symptomatic AEs with their medications that are bothersome. Further work is needed to develop and validate a measure for use in patients with rheumatic disease.

Patient and rheumatologist perspectives on tapering DMARDs in rheumatoid arthritis: a qualitative study.

OBJECTIVES: To understand the perspectives of patients and rheumatologists for tapering DMARDs in RA. METHODS: Using semi-structured interview guides, we conducted individual interviews and focus groups with RA patients and rheumatologists, which were audiotaped and transcribed. We conducted a pragmatic thematic analysis to identify major themes, comparing and contrasting different views on DMARD tapering between patients and rheumatologists. RESULTS: We recruited 28 adult patients with RA (64% women; disease duration 1-54 y) and 23 rheumatologists (52% women). Attitudes across both groups towards tapering DMARDs were ambivalent, ranging from wary to enthusiastic. Both groups expressed concerns, particularly the inability to 'recapture' the same level of disease control, while also acknowledging potential positive outcomes such as reduced drug harms. Patient tapering perspectives (whether to and when) changed over time and commonly included non-biologic DMARDs. Patient preferences were influenced by lived experiences, side effects, previous tapering experiences, disease trajectory, remission duration and current life roles. Rheumatologists' perspectives varied on timing and patient profile to initiate tapering, and were informed by both data and clinical experience. Patients expressed interest in shared decision-making (SDM) and close monitoring during tapering, with ready access to their health-care team if problems arose. Rheumatologists were generally open to tapering (not stopping), though sometimes only when requested by their patients. CONCLUSION: The perspectives of patients and rheumatologists on tapering DMARDs in RA vary and evolve over time. Rheumatologists should periodically discuss DMARD tapering with patients as part of SDM, and ensure monitoring and flare management plans are in place.

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

OBJECTIVE: To compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

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.

Canadian Rheumatology Association Recommendation for the Use of COVID-19 Vaccination for Patients With Autoimmune Rheumatic Diseases.

OBJECTIVE: To develop guidance on the use of coronavirus disease 2019 (COVID-19) vaccines in patients with autoimmune rheumatic diseases (ARD). METHODS: The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel including rheumatologists, researchers, methodologists, vaccine experts, and patients. The panel used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Outcomes were prioritized according to their importance for patients and clinicians. Evidence from the COVID-19 clinical trials was summarized. Indirect evidence for non-COVID-19 vaccines in ARD was also considered. The GRADE evidence-to-decision (EtD) framework was used to develop a recommendation for the use of the 4 COVID-19 vaccines approved in Canada as of March 25, 2021 (BNT162b2, mRNA-1273, ChAdOx1, and Ad26.COV2.S), over 4 virtual panel meetings. RESULTS: The CRA guideline panel suggests using COVID-19 vaccination in persons with ARD. The panel unanimously agreed that for the majority of patients, the potential health benefits of vaccination outweigh the potential harms in people with ARDs. The recommendation was graded as conditional because of low or very low certainty of the evidence on the effects in the population of interest, primarily due to indirectness and imprecise effect estimates. The panel felt strongly that persons with autoimmune rheumatic diseases who meet local eligibility should not be required to take additional steps compared to people without ARDs to obtain their vaccination. Guidance on medications, implementation, monitoring of vaccine uptake, and research priorities are also provided. CONCLUSION: This recommendation will be updated over time as new evidence emerges, with the latest recommendation, evidence summaries, and EtD available on the CRA website.

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.