ObjectiveTo jointly estimate American College of Rheumatology (ACR50) response (a more commonly r... more ObjectiveTo 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).MethodsWe 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.ResultsFrom 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 combinati...
Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in r... more Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A t...
ABSTRACT. Objective. To characterize the safety of rituximab (RTX) in combination with biologic d... more ABSTRACT. Objective. To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA). Methods. We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients' current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment.
To investigate the relationship between function and disease activity in early inflammatory arthr... more To investigate the relationship between function and disease activity in early inflammatory arthritis (EIA). Canadian Early Arthritis Cohort (CATCH) (n=1143) is a multi-site EIA cohort. Correlations between the Health Assessment Questionnaire Disability Index (HAQ) and DAS28 were done at every 3 months for the first year and then at 18 and 24 months. We also investigated the relationship between HAQ and DAS28 by age (<65 versus ≥65) and RF (positive vs negative). Mean HAQ and DAS28 scores were highest at the initial visit with HAQ decreasing over 24 months from a baseline of 0.94 to 0.40 and DAS28 scores decreasing from 4.54 to 2.29. All correlations between HAQ and DAS28 were significant at all time points (p<0.01). The correlations between HAQ and DAS28 were variable over time. The strongest correlation between HAQ and DAS28 occurred at initial visit (most DMARD naive) (n=1,143) and 18 months (r=0.57, n=321) and 24 months (r=0.59, n=214). The baseline correlation between HAQ...
ObjectiveEarly rheumatoid arthritis (RA) treatment requires timely recognition. This large, multi... more 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 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.ResultsIn 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...
ObjectivesSecondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but l... more ObjectivesSecondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but little is known about its incidence and the factors leading to its development. The authors examined the incidence of secondary FM in an early inflammatory arthritis cohort, and assessed the association between pain, inflammation, psychosocial variables and the clinical diagnosis of FM.MethodsData from 1487 patients in the Canadian Early Arthritis Cohort, a prospective, observational Canadian cohort of early inflammatory arthritis patients were analysed. Diagnoses of FM were determined by rheumatologists. Incidence rates were calculated, and Cox regression models were used to determine HRs for FM risk.ResultsThe cumulative incidence rate was 6.77 (95% CI 5.19 to 8.64) per 100 person-years during the first 12 months after inflammatory arthritis diagnosis, and decreased to 3.58 (95% CI 1.86 to 6.17) per 100 person-years 12–24 months after arthritis diagnosis. Pain severity (HR 2.01, 95% CI ...
Clinical medicine insights. Arthritis and musculoskeletal disorders, 2016
The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase ... more The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was -26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0...
Our objective was to identify distinct trajectories of disease activity state (DAS) and assess va... more Our objective was to identify distinct trajectories of disease activity state (DAS) and assess variation in radiographic progression, function and quality of life over the first two years of early rheumatoid arthritis (ERA). The CATCH (Canadian early ArThritis CoHort) is a prospective study recruiting ERA patients from academic and community rheumatology clinics in Canada. Sequential DAS28 scores were used to identify five mutually exclusive groups in the cohort (n = 1,586) using growth-based trajectory modeling. Distinguishing baseline sociodemographic and disease variables, treatment required, and differences in radiographic progression and quality of life measures over two years were assessed. The trajectory groups are characterized as: Group 1 (20%) initial high DAS improving rapidly to remission (REM); Group 2 (21%) initial moderate DAS improving rapidly to REM; Group 3 (30%) initial moderate DAS improving gradually to low DAS; Group 4 (19%) initial high DAS improving continuou...
To assess the effect of socioeconomic status (SES) on outcomes in patients with early inflammator... more 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. 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. 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). Pati...
Objective.To systematically identify and examine reports of sex-stratified pain measurements in p... more Objective.To systematically identify and examine reports of sex-stratified pain measurements in patients with inflammatory arthritis.Methods.Data sources included PubMed (1950 to April 2010), Embase (1980 to April 2010), and manual searches of reference lists and conference abstracts. We included cohort studies and randomized trials comparing pain scores, treatment efficacy at reducing pain, or pain localization, between females and males with inflammatory arthritis [rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and reactive arthritis].Results.Twenty-six cohorts and 1 randomized trial reported sex-stratified pain scores, and all but 1 cohort identified worse pain scores at enrollment in females. In a metaanalysis of mean visual analog scale (VAS) scores (0 to 10) in 16 RA cohort studies (reporting on 21,612 females and 6871 males), the standardized mean difference in VAS was 0.21 (95% CI 0.16, 0.26). Treatment with disease-modifying therapy results in impro...
Objective.To determine the proportion of patients with early inflammatory arthritis in a Canadian... more Objective.To determine the proportion of patients with early inflammatory arthritis in a Canadian cohort who are at high risk for a major osteoporotic fracture using the Fracture Risk Assessment Tool (FRAX®), and to determine if a care gap exists in high-risk patients.Methods.FRAX was applied to 238 patients enrolled in the Canadian Early Arthritis Cohort (CATCH) study based on norms from the United States and the United Kingdom, without the use of bone mineral density measurements.Results.FRAX identified 5%–13% of patients at high risk for fracture, using a conservative analysis. Based on US norms, there was a significant correlation between increasing fracture risk groups and oral glucocorticoid use (p = 0.012) and baseline erosions (p = 0.040). Calcium or vitamin D use did not vary among the different fracture risk groups (p = NS), nor did bisphosphonate use (p = NS). The Disease Activity Score with 28 joint count in the high-risk group was significantly higher compared to the lo...
ObjectiveTo jointly estimate American College of Rheumatology (ACR50) response (a more commonly r... more ObjectiveTo 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).MethodsWe 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.ResultsFrom 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 combinati...
Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in r... more Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A t...
ABSTRACT. Objective. To characterize the safety of rituximab (RTX) in combination with biologic d... more ABSTRACT. Objective. To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA). Methods. We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients' current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment.
To investigate the relationship between function and disease activity in early inflammatory arthr... more To investigate the relationship between function and disease activity in early inflammatory arthritis (EIA). Canadian Early Arthritis Cohort (CATCH) (n=1143) is a multi-site EIA cohort. Correlations between the Health Assessment Questionnaire Disability Index (HAQ) and DAS28 were done at every 3 months for the first year and then at 18 and 24 months. We also investigated the relationship between HAQ and DAS28 by age (<65 versus ≥65) and RF (positive vs negative). Mean HAQ and DAS28 scores were highest at the initial visit with HAQ decreasing over 24 months from a baseline of 0.94 to 0.40 and DAS28 scores decreasing from 4.54 to 2.29. All correlations between HAQ and DAS28 were significant at all time points (p<0.01). The correlations between HAQ and DAS28 were variable over time. The strongest correlation between HAQ and DAS28 occurred at initial visit (most DMARD naive) (n=1,143) and 18 months (r=0.57, n=321) and 24 months (r=0.59, n=214). The baseline correlation between HAQ...
ObjectiveEarly rheumatoid arthritis (RA) treatment requires timely recognition. This large, multi... more 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 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.ResultsIn 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...
ObjectivesSecondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but l... more ObjectivesSecondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but little is known about its incidence and the factors leading to its development. The authors examined the incidence of secondary FM in an early inflammatory arthritis cohort, and assessed the association between pain, inflammation, psychosocial variables and the clinical diagnosis of FM.MethodsData from 1487 patients in the Canadian Early Arthritis Cohort, a prospective, observational Canadian cohort of early inflammatory arthritis patients were analysed. Diagnoses of FM were determined by rheumatologists. Incidence rates were calculated, and Cox regression models were used to determine HRs for FM risk.ResultsThe cumulative incidence rate was 6.77 (95% CI 5.19 to 8.64) per 100 person-years during the first 12 months after inflammatory arthritis diagnosis, and decreased to 3.58 (95% CI 1.86 to 6.17) per 100 person-years 12–24 months after arthritis diagnosis. Pain severity (HR 2.01, 95% CI ...
Clinical medicine insights. Arthritis and musculoskeletal disorders, 2016
The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase ... more The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was -26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0...
Our objective was to identify distinct trajectories of disease activity state (DAS) and assess va... more Our objective was to identify distinct trajectories of disease activity state (DAS) and assess variation in radiographic progression, function and quality of life over the first two years of early rheumatoid arthritis (ERA). The CATCH (Canadian early ArThritis CoHort) is a prospective study recruiting ERA patients from academic and community rheumatology clinics in Canada. Sequential DAS28 scores were used to identify five mutually exclusive groups in the cohort (n = 1,586) using growth-based trajectory modeling. Distinguishing baseline sociodemographic and disease variables, treatment required, and differences in radiographic progression and quality of life measures over two years were assessed. The trajectory groups are characterized as: Group 1 (20%) initial high DAS improving rapidly to remission (REM); Group 2 (21%) initial moderate DAS improving rapidly to REM; Group 3 (30%) initial moderate DAS improving gradually to low DAS; Group 4 (19%) initial high DAS improving continuou...
To assess the effect of socioeconomic status (SES) on outcomes in patients with early inflammator... more 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. 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. 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). Pati...
Objective.To systematically identify and examine reports of sex-stratified pain measurements in p... more Objective.To systematically identify and examine reports of sex-stratified pain measurements in patients with inflammatory arthritis.Methods.Data sources included PubMed (1950 to April 2010), Embase (1980 to April 2010), and manual searches of reference lists and conference abstracts. We included cohort studies and randomized trials comparing pain scores, treatment efficacy at reducing pain, or pain localization, between females and males with inflammatory arthritis [rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and reactive arthritis].Results.Twenty-six cohorts and 1 randomized trial reported sex-stratified pain scores, and all but 1 cohort identified worse pain scores at enrollment in females. In a metaanalysis of mean visual analog scale (VAS) scores (0 to 10) in 16 RA cohort studies (reporting on 21,612 females and 6871 males), the standardized mean difference in VAS was 0.21 (95% CI 0.16, 0.26). Treatment with disease-modifying therapy results in impro...
Objective.To determine the proportion of patients with early inflammatory arthritis in a Canadian... more Objective.To determine the proportion of patients with early inflammatory arthritis in a Canadian cohort who are at high risk for a major osteoporotic fracture using the Fracture Risk Assessment Tool (FRAX®), and to determine if a care gap exists in high-risk patients.Methods.FRAX was applied to 238 patients enrolled in the Canadian Early Arthritis Cohort (CATCH) study based on norms from the United States and the United Kingdom, without the use of bone mineral density measurements.Results.FRAX identified 5%–13% of patients at high risk for fracture, using a conservative analysis. Based on US norms, there was a significant correlation between increasing fracture risk groups and oral glucocorticoid use (p = 0.012) and baseline erosions (p = 0.040). Calcium or vitamin D use did not vary among the different fracture risk groups (p = NS), nor did bisphosphonate use (p = NS). The Disease Activity Score with 28 joint count in the high-risk group was significantly higher compared to the lo...
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