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The Canadian Tofacitinib for Rheumatoid Arthritis Observational (CANTORAL) is the first Canadian prospective, observational study assessing tofacitinib. The objective was to assess effectiveness and safety for moderate to severe rheumatoid arthritis (RA). Coprimary and secondary outcomes are reported from an interim analysis. Patients initiating tofacitinib from October 2017 to July 2020 were enrolled from 45 Canadian sites. Coprimary outcomes (month 6) included the Clinical Disease Activity Index (CDAI)–defined low disease activity (LDA) and remission. Secondary outcomes (to month 18) included the CDAI and the 4‐variable Disease Activity Score in 28 joints (DAS28) using the erythrocyte sedimentation rate (ESR)/C‐reactive protein (CRP) level to define LDA and remission; the proportions of patients achieving mild pain (visual analog scale <20 mm), and moderate (≥30%) and substantial (≥50%) pain improvements; and the proportions of patients achieving a Health Assessment Questionnaire disability index (HAQ DI) score greater or equal to  normative values (≤0.25) and a HAQ DI score greater or equal to minimum clinically important difference (MCID) (≥0.22). Safety was assessed to month 36. Of 504 patients initiating tofacitinib, 44.4% received concomitant methotrexate. At month 6, 52.9% and 15.4% of patients were in CDAI‐defined LDA and remission, respectively; a similar proportion of patients achieved outcomes by month 3 (first post‐baseline assessment). By month 3, 27.2% and 41.7% of patients, respectively, were in DAS28‐ESR–defined LDA and DAS28‐CRP <3.2; 14.7% and 25.8% achieved DAS28‐ESR remission and DAS28‐CRP <2.6. By month 3, mild pain and moderate and substantial pain improvements occurred in 29.6%, 55.6%, and 42.9% of patients, respectively; 19.9% and 53.7% of patients achieved a HAQ DI score greater than or equal to normative values and a HAQ DI score greater than or equal to MCID, respectively. Outcomes were generally maintained to month 18. Incidence rates (events per 100 patient‐years) for treatment‐emergent adverse events (AEs), serious AEs, and discontinuations due to AEs were 126.8, 11.9, and 14.5, respectively, and AEs of special interest were infrequent. Tofacitinib was associated with early and sustained improvement in RA signs and symptoms in real‐world patients. Effectiveness and safety were consistent with the established tofacitinib clinical profile.

Introduction: The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA). Methods: Patients aged ≥ 18 years with active RA and an inadequate response to MTX received open-label tofacitinib modified-release 11 mg once daily plus MTX for 24 weeks. In the double-blind MTX withdrawal phase, those who had achieved CDAI LDA (≤ 10) at week 24 were randomised 1:1 to receive tofacitinib monotherapy or continued tofacitinib plus MTX. Efficacy analyses were performed in subgroups defined by whether remission and/or LDA had been achieved at week 24 with: Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)], Routine Assessment of Patient Index Data 3 (RAPID3), CDAI and Simplified Disease Activity Index (SDAI); or DAS28-4[C-reactive protein(CRP)] &lt; 2.4/ &lt; 2.6/ &lt; 2.9/ ≤ 3.2. Results: Five hundred and thirty patients received treatment in the double-blind MTX withdrawal phase. Proportions of patients achieving each disease activity criterion at week 24 varied by metric. Across disease activity metrics [excluding DAS28-4(ESR) remission], 58–89% of patients per group, and numerically more patients receiving tofacitinib plus MTX, achieved the same criterion at week 48 as at week 24. Differences between groups in least squares mean change from baseline (Δ) DAS28-4(ESR) from week 24–48 favoured tofacitinib plus MTX (nominal pvalues &lt; 0.05). RAPID3 and DAS28-4(CRP) estimated a higher proportion of patients with acceptable disease state versus DAS28-4(ESR), CDAI remission and SDAI remission. Conclusion: Response rates at the beginning of the double-blind phase varied across metrics. A consistent trend towards higher response rates with tofacitinib plus MTX was observed across metrics after randomisation, with nominal differences in DAS28-4(ESR) responses. Compared with continued combination therapy, MTX withdrawal did not lead to a clinically meaningful reduction in the response to tofacitinib. DAS28-4(CRP) and RAPID3 were the least stringent metrics. Trial Registration: ClinicalTrials.gov identifier: NCT02831855.

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). We studied a multicenter, incident early RAcohort (enrolled 2007–2017 within 1 year of symptoms) who fulfilled American College of Rheumatology/European League Against Rheumatism criteria. Adult patients with RAwere 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 MTXmonotherapy, adding or stopping a DMARDor biologic, and changing dose/frequency of a DMARDor biologic. There was great variability of treatment at initiation and during therapy adjustment. In 1,484 patients with early RA, the majority initiated MTXmonotherapy (oral or subcutaneous [SC]). Patients receiving SC MTXmonotherapy 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 MTXmonotherapy. Most therapy adjustments involved adding a DMARDor changing to a non‐MTX DMARD. Those adults taking biologics and who were receiving triple therapy had a longer time without treatment change (HR0.26 [95% CI0.16–0.42] and HR0.57 [95% CI0.38–0.85], respectively). We found large variability in the way MTX‐based therapies are prescribed in clinical practice. Our findings support the use of SC MTXmonotherapy or MTXcombination 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 MTXmonotherapy.

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. 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. 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. 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.

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.

To assess adherence to 3 system‐level performance measures in a national early rheumatoid arthritis (RA) cohort. 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 RApatients seen in yearly followup, and the number of gaps between visits of >12 or >14 months, the percentage of RApatients treated with a disease‐modifying antirheumatic drug (DMARD), and days from RAdiagnosis to initiation of a DMARD. Results are shown stratified by enrollment year to assess for temporal changes in performance. A total of 1,763 early RApatients were included (mean age 54 years, 73% female, and 82% white). At enrollment, mean ± SDdisease 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 RApatients was and remained high (95–87%), and the percentage receiving DMARDs within 14 days of diagnosis was 75%. Median time‐to‐DMARDtherapy was 1 day, indicating DMARDs were initiated at diagnosis (90th percentile 93 days). There was evidence of high adherence to system‐level performance measures in this early RAcohort following a protocol. Small declines in performance were noted with increasing length of patient followup. Our findings are useful for performance measure benchmarking.

Objective.To assess the effect of socioeconomic status (SES) on outcomes in patients with early inflammatory arthritis, using data from the Canadian Early Arthritis Cohort (CATCH) study.Methods.In an incident cohort, 2023 patients were recruited, and allocated to low SES or high SES groups based on education and income. Outcomes at baseline and 12 months were analyzed in relation to SES including the 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), pain, patient’s global assessment scale (PtGA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and the SF12-v2 Health Survey, using the ANOVA, chi-squared test, and regression analyses.Results.The CATCH population had 43% with high school education or less and 37% in the low-income group (< 50,000 Can$ per annum household income). The low-education group had higher DAS28 at baseline (p = 0.045), becoming nonsignificant at 12 months and lower physical component score on SF12-v2 at baseline (p = 0.022). Patients in the low-income group presented with higher HAQ-DI (p = 0.017), pain (p = 0.035), PtGA (p = 0.004), and SDAI (p = 0.022). Low-income versus high-income groups were associated with an OR above the median for HAQ-DI (1.20; 95% CI 1.00–1.45), PtGA (1.27; 95% CI 1.06–1.53), and SDAI (1.25; 95% CI 1.02–1.52) at baseline. The association with low income persisted at 12 months for HAQ-DI (OR 1.30; 95% CI 1.02–1.67), but not for other variables.Conclusion.Low SES was initially associated with higher disease activity, pain, and PtGA, and poorer function. At 1 year, outcomes were similar to those with high SES, with the exception of HAQ-DI.

The risk of serious infectious events (SIEs) is increased in patients with rheumatoid arthritis (RA). The aim of this study was to develop an age-adjusted comorbidity index (AACI) to predict, using baseline characteristics, the SIE risk in patients with RA treated with certolizumab pegol (CZP). Data of CZP-treated patients with RA were pooled from the RAPID1/RAPID2 randomized controlled trials (RCT CZP) and their open-label extensions (All CZP). Predictors of the first SIE were examined using multivariate Cox models. The AACI was developed by assigning specific weights to patient age and comorbidities on the basis of relative SIE risk. SIE rates were predicted using AACI score and baseline glucocorticoid use, and they were compared with observed rates. The percentage of patients in each SIE risk group achieving low disease activity (LDA)/remission was examined at 1 year of treatment. Among 1224 RCT CZP patients, 40 reported ≥ 1 SIE (incidence rate [IR] 5.09/100 patient-years [PY]), and 201 of 1506 All CZP patients reported ≥ 1 SIE (IR 3.66/100 PY). Age ≥ 70 years, diabetes mellitus, and chronic obstructive pulmonary disease/asthma made the greatest contributions to AACI score. SIE rates predicted using AACI and glucocorticoid use at baseline showed good agreement with observed SIE rates across low-risk and high-risk groups. At 1 year, more high-risk All CZP patients than low-risk All CZP patients reported SIEs (IR 8.4/100 PY vs. IR 3.4/100 PY). Rates of LDA/remission were similar between groups. AACI and glucocorticoid use were strong baseline predictors of SIE risk in CZP-treated patients with RA. Predicted SIE risk was not associated with patients’ likelihood of clinical response. This SIE risk score may provide a valuable tool for clinicians when considering the risk of infection in individual patients with RA. ClinicalTrials.gov, NCT00152386(registered 7 September 2005); NCT00160602(registered 8 September 2005); NCT00175877(registered 9 September 2005); and NCT00160641(registered 8 September 2005).

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). 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. 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. 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.

Objective.To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort.Methods.Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made among sites in change in 28-joint Disease Activity Score (DAS28), proportion of patients in DAS28 remission, and treatment strategies.Results.The study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor-positive; 37% anticitrullinated protein antibody-positive; disease duration 187 (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best changes in DAS28 (−1.82 and −2.09, respectively, at 6 mos, and −2.27 for both at 12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months [64.5% compared to other sites that had from 34.1% to 51.7% (p < 0.001)], and at the last followup, sites B and H had the most in remission. Subcutaneous methotrexate was used more overall and earlier at sites B and H. Those sites used less steroid therapy, and site B had the second-highest use of triple disease-modifying antirheumatic drugs at any visit. Medications were increased more in 2 of the 3 smallest sites. Biologics were used by 9 months most in the smallest (50.0%) and then largest (19.6%) sites.Conclusion.Sites in an early inflammatory arthritis cohort yielded different outcomes. Better outcomes up to 12 months may result from initial treatment with early combination therapy and/or subcutaneous methotrexate.

To date, head-to-head trials comparing the efficacy and safety of biological disease-modifying antirheumatic drugs within the same class, including TNF inhibitors, in patients with active rheumatoid arthritis despite methotrexate therapy are lacking. We aimed to compare the efficacy and safety of two different TNF inhibitors and to assess the efficacy and safety of switching to the other TNF inhibitor without a washout period after insufficient primary response to the first TNF inhibitor at week 12.