To describe disease expression and damage accrual in systemic lupus erythematosus (SLE), and determine the influence of ethnicity and socioeconomic factors on damage accrual in a large multiethnic Canadian cohort.
Adults with SLE were enrolled in a multicenter cohort. Data on sociodemographic factors, diagnostic criteria, disease activity, autoantibodies, treatment, and damage were collected using standardized tools, and results were compared across ethnic groups. We analyzed baseline data, testing for differences in sociodemographic and clinical factors, between the different ethnic groups, in univariate analyses; significant variables from univariate analyses were included in multivariate regression models examining for differences between ethnic groups, related to damage scores.
We studied 1416 patients, including 826 Caucasians, 249 Asians, 122 Afro-Caribbeans, and 73 Aboriginals. Although the overall number of American College of Rheumatology criteria in different ethnic groups was similar, there were differences in individual manifestations and autoantibody profiles. Asian and Afro-Caribbean patients had more frequent renal involvement and more exposure to immunosuppressives. Aboriginal patients had high frequencies of antiphospholipid antibodies and high rates of comorbidity, but disease manifestations similar to Caucasians. Asian patients had the youngest age at onset and the lowest damage scores. Aboriginals had the least education and lowest incomes. The final regression model (R2=0.27) for higher damage score included older age, longer disease duration, low income, prednisone treatment, higher disease activity, and cyclophosphamide treatment.
There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.
Health administrative data can be a valuable tool for disease surveillance and research. Few studies have rigorously evaluated the accuracy of administrative databases for identifying rheumatoid arthritis (RA) patients. Our aim was to validate administrative data algorithms to identify RA patients in Ontario, Canada.
We performed a retrospective review of a random sample of 450 patients from 18 rheumatology clinics. Using rheumatologist-reported diagnosis as the reference standard, we tested and validated different combinations of physician billing, hospitalization, and pharmacy data.
One hundred forty-nine rheumatology patients were classified as having RA and 301 were classified as not having RA based on our reference standard definition (study RA prevalence 33%). Overall, algorithms that included physician billings had excellent sensitivity (range 94-100%). Specificity and positive predictive value (PPV) were modest to excellent and increased when algorithms included multiple physician claims or specialist claims. The addition of RA medications did not significantly improve algorithm performance. The algorithm of "(1 hospitalization RA code ever) OR (3 physician RA diagnosis codes [claims] with =1 by a specialist in a 2-year period)" had a sensitivity of 97%, specificity of 85%, PPV of 76%, and negative predictive value of 98%. Most RA patients (84%) had an RA diagnosis code present in the administrative data within ±1 year of a rheumatologist's documented diagnosis date.
We demonstrated that administrative data can be used to identify RA patients with a high degree of accuracy. RA diagnosis date and disease duration are fairly well estimated from administrative data in jurisdictions of universal health care insurance.
In inflammatory arthritis, rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe clinical outcomes. Our objective was to determine whether ACPA and RF remain stable in early inflammatory arthritis and whether their trajectories over time or baseline levels predicted clinical outcomes.
The study population consisted of patients enrolled in the Canadian Early Arthritis Cohort Study with baseline and at least 12-month followup values of RF and ACPA. Primary outcomes were Disease Activity Score (DAS) remission and the presence of erosions at 12 and 24 months. Other objectives included swollen joint count, Health Assessment Questionnaire score, and DAS.
At baseline, 225/342 (66%) patients were ACPA-positive and 334/520 (64%) were RF-positive. At 24 months, 15/181 (8%) ACPA-positive patients became negative. A larger number of patients changed from ACPA-negative to positive: 13/123 (11%). For RF, fluctuations were more common: 67/240 (28%) reverted from positive to negative and 21/136 (18%) converted from negative to positive. RF and ACPA fluctuations did not predict disease outcomes. Patients who remained ACPA-positive throughout followup were more likely to have erosive disease (OR 3.86, 95% CI 1.68, 8.92).
RF and ACPA have the potential to revert and convert during the early course of disease. Fluctuations in RF and ACPA were not associated with clinical outcomes.
The aim of this study was to determine the impact of age on disease and remission in suspected early RA (ERA).
Data from the Canadian Early Arthritis Cohort (CATCH) were examined at baseline, 6 and 12 months. Patients were divided into three groups based on age. Analysis of variance (ANOVA) and regression models were performed to determine the impact of age on the 28-joint DAS (DAS28) and remission at 12 months.
A total of 1809 patients were initially assessed: 442 (24.4%) young (
The Canadian Early Arthritis Cohort (CATCH): patients with new-onset synovitis meeting the 2010 ACR/EULAR classification criteria but not the 1987 ACR classification criteria present with less severe disease activity.
Our objective was to describe characteristics of Canadian patients with early arthritis and examine differences between those fulfilling 1987 and 2010 rheumatoid arthritis (RA) classification criteria.
The Canadian Early Arthritis Cohort (CATCH) is a national, multicenter, observational, prospective cohort of patients with early inflammatory arthritis, receiving usual care, recruited since 2007. Inclusion criteria include age > 16 years; symptom duration 6-52 weeks; swelling of = 2 joints or = 1 metacarpophalangeal/proximal interphalangeal joint; and 1 of rheumatoid factor = 20 IU, positive anticitrullinated protein antibodies (ACPA), morning stiffness = 45 min, response to nonsteroidal antiinflammatory drug, or positive metatarsophalangeal joint squeeze test. Data from patients enrolled to March 15, 2011, were analyzed.
In total, 1450 patients met the eligibility criteria (1187 were followed). At baseline, mean age was 53 ± 15 years, symptom duration was 6.1 ± 3.2 months, Disease Activity Score (DAS28) was 4.9 ± 1.6, Health Assessment Questionnaire-Disability Index was 1.0 ± 0.7. Forty-one percent (n = 450) of patients had moderate (3.2 5.1) disease activity; 28% of those with baseline radiographs (n = 250/908) had radiographic evidence of erosions. ACPA status was available for 70% (n = 831) of patients; 55% (n = 453) tested positive. Sixty percent (n = 718) of patients were treated with methotrexate (MTX) initially. Of 612 patients without erosions, 63% and 83% fulfilled 1987 and 2010 RA classification criteria, respectively. Seventy-three percent (n = 166) of those who did not fulfill 1987 criteria were newly identified by the 2010 criteria. These patients had less severe disease and more were MTX-naive compared to those satisfying the 1987 criteria. Forty-seven percent of all patients achieved remission at 1 year.
Patients with early RA present with moderate high disease activity;
Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.
Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.
Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS = 3 tender joints using 28-joint count (TJC28) PLUS = 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS = 3 TJC28 PLUS = 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.
There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.
We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy.
Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy.
In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p
To update estimates of cancer risk in SLE relative to the general population.
A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers.
Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23).
These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
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.
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.
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 low-risk group (p = 0.048).
Patients at increased risk had higher disease activity, more frequent glucocorticoid use, and more baseline erosions compared to patients at low risk. A care gap exists, in that a very low proportion of patients at high risk are being treated with calcium, vitamin D, and/or bisphosphonates. A higher fracture risk was calculated in our cohort using the US FRAX calculation tool compared to the UK calculation tool. These data highlight the need to identify and modify fracture risk in patients with early inflammatory arthritis.