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Objective. Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab (SEC) is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials; however, there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC among Canadian patients with PsA. Methods. This was an observational cohort study of Canadian patients with PsA, 18 to 65 years of age, who attended a clinic of the CanSpA network and received treatment with SEC. Patients were indexed on the date they first initiated SEC. Retention was assessed at 12 months postindex. Clinical effectiveness was measured as the proportion of patients in remission and change in disease activity from baseline to 12 months using several clinical indices. Results. In total, 213 patients were included. Overall retention was estimated at 73.6% at 12 months (81.8% for bDMARD- or targeted synthetic DMARD-naïve patients). Out of 110 patients, 17 (15.5%) were in remission based on the Disease Activity Index in Psoriatic Arthritis in 28 joints, and 10 out of 70 patients (14.3%) were in remission based on the Psoriatic Arthritis Disease Activity Score at 12 months. The Psoriasis Area and Severity Index improved by 65.8%; the tender joint count in 68 joints and the swollen joint count in 66 joints improved by 65.5% and 73.7%, respectively. Conclusion. This is the first nationwide study that we know of to describe real-world use of SEC in Canada for PsA, and the results support its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada. [ABSTRACT FROM AUTHOR]

Objective. Axial spondyloarthritis (axSpA) is a chronic, immune-mediated, inflammatory condition consisting of 2 clinical subsets: nonradiographic axSpA and ankylosing spondylitis, the latter having an estimated prevalence of 0.2% to 1% in Canada. Secukinumab (SEC) received Health Canada approval in 2016 for the treatment of adults with axSpA who have responded inadequately to conventional treatment, and has demonstrated efficacy and safety through extensive clinical trials. However, there is limited evidence on its real-world use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC in the Canadian axSpA population. Methods. This was an observational cohort study of Canadian patients with axSpA aged 18 to 65 years within the CanSpA network who had received treatment with SEC. Patients were indexed on the first date of SEC initiation. Retention and clinical effectiveness were assessed at 12 months postindex. Clinical effectiveness was measured as the proportion in remission and change in disease activity using multiple clinical indices. Results. A total of 146 patients were included. Overall retention was estimated at 62.9%. Low disease activity (ie, Bath Ankylosing Spondylitis Disease Activity Index < 4) was achieved in 29.2% of patients, and 2% had achieved remission based on the Ankylosing Spondylitis Disease Activity Score. Bath Ankylosing Spondylitis Metrology Index scores improved by more than 60% from baseline to 12 months. Conclusion. The results of this real-world study of Canadian patients with axSpA, one of the first of its kind, support the effectiveness of SEC for treatment of axSpA. The CanSpA network presents an opportunity to continue building and improving the real-world evidence base for treatment of Canadian patients with spondyloarthritis. [ABSTRACT FROM AUTHOR]

Objective: Psoriatic arthritis (PsA) substantially impairs quality of life. Clinical trials generally focus on polyarticular PsA, but less is known about the assessment and management of oligoarticular and moderate PsA. An online survey was conducted to determine Canadian rheumatologists' perspectives on the definition and treatment of oligoarticular and moderate PsA.Methods: Regional and national experts treating patients with PsA were asked to complete an online survey to assess their approach to identifying and managing patients with PsA. Survey questions were developed based on guidance from a committee of Canadian rheumatologists.Results: Sixty-four of 78 rheumatologists responded, representing 6 major Canadian provinces. Nearly half of respondents were in practice > 20 years. The majority of rheumatologists reported using swollen joint count (SJC) to describe moderate PsA (86.4%) and oligoarticular PsA (96.7%), and considered location of inflammation in PsA assessments. SJC cutoff scores for reporting moderate PsA varied among rheumatologists, suggesting lack of an agreed-upon definition for moderate PsA. Sixty-eight percent of rheumatologists identified access to treatment as the greatest challenge with oligoarticular PsA.Conclusion: According to the surveyed rheumatologists, SJC remains a key assessment variable when defining oligoarticular and moderate PsA. Although the number of joints is considered when determining the effect of PsA on patients, joint location and functional impairment are also considered when describing the disease as moderate. Access to treatment for patients with < 5 affected joints is challenging. [ABSTRACT FROM AUTHOR]

Objective: To describe the radiographic phenotype of axial spondyloarthritis (SpA) according to the presence of HLA-B27.Methods: An international collaboration compared the radiographic phenotype of axial SpA according to HLA-B27 status. Patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA) were collected. Radiographs were read centrally, blinded to clinical details. The symmetry of the sacroiliac joints and lumbar syndesmophytes and the morphology of syndesmophytes (typical marginal versus atypical chunky), together with the modified Stoke Ankylosing Spondylitis Spine Score and the Psoriatic Arthritis Spondylitis Radiographic Index, were recorded.Results: A total of 244 patients with PsA and 198 patients with AS were included. In PsA, 60 patients (25%) were HLA-B27 positive while in AS, 148 patients (75%) were HLA-B27 positive. Patients with HLA-B27 were younger and more often male and had a longer duration of disease. In multivariable logistic regression, HLA-B27 was significantly associated with syndesmophyte symmetry (odds ratio [OR] 3.02 [95% confidence interval (95% CI) 1.38, 6.61]) and marginal syndesmophytes (OR 1.97 [95% CI 1.16, 3.36]) but not with sacroiliac symmetry. Mean radiographic scores were higher for patients with HLA-B27.Conclusion: Patients with axial SpA who are positive for HLA-B27 have more severe radiographic damage, more marginal syndesmophytes, and more frequent syndesmophyte symmetry compared to patients who are negative for HLA-B27. [ABSTRACT FROM AUTHOR]

Objective: The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis (PsA). We aimed to validate a cutoff value of PASDAS that defines minimal disease activity (MDA) state, as well as to validate previously defined PASDAS cutoffs for low and high disease activity.Methods: Patients were prospectively recruited from the University of Toronto PsA clinic according to a standard protocol, and variables necessary to complete the PASDAS and the MDA were collected. Receiver-operating characteristic (ROC) curve analysis determined the optimal PASDAS cutoff discriminating patients in MDA state from those not in MDA. Previously proposed PASDAS disease activity cutoff scores were validated by determining the proportion of patients requiring treatment escalation, a surrogate of active disease, in each of low, moderate, and high disease activity groups.Results: One hundred seventy-eight patients [53.9% male, mean PASDAS 3.29 (SD 1.29), 47.8% in MDA] were recruited. ROC curve analysis identified a PASDAS score of 3.2 as the point that maximized the sensitivity and specificity for MDA based on 5 of 7 criteria (sensitivity 88%, specificity 92%, area under the curve 0.96). For MDA based on meeting 6 of 7 and 7 of 7 criteria, PASDAS scores of 2.6 and 2.1 maximized sensitivity and specificity, respectively. An increasing proportion of patients from low to moderate to high disease activity groups required treatment escalation, increasing from 8.1% to 42% to 67%, respectively.Conclusion: A PASDAS score < 3.2 reflects MDA. This study has externally validated PASDAS cutoff scores previously proposed to differentiate between low, moderate, and high disease activity. [ABSTRACT FROM AUTHOR]

Objective To estimate the incidence of psoriatic arthritis (PsA) in patients with psoriasis, and to identify risk factors for its development. Methods The study was designed as a prospective cohort study involving psoriasis patients who did not have a diagnosis of arthritis at the time of study enrollment. Information was collected about lifestyle habits, comorbidities, psoriasis activity, and medications. Patients who developed inflammatory arthritis or spondylitis were classified as having PsA if they fulfilled the criteria of the Classification of Psoriatic Arthritis Study group. The annual incidence of PsA was estimated using an event per person-years analysis. Cox proportional hazards models, involving fixed and time-dependent explanatory variables, were fitted to obtain estimates of the relative risk (RR) of the onset of PsA, determined in multivariate models stratified by sex and controlled for age at onset of psoriasis. Results The data obtained from the 464 patients who were followed up for 8 years were analyzed. A total of 51 patients developed PsA during the 8 years since enrollment. The annual incidence rate of PsA was 2.7 cases (95% confidence interval 2.1-3.6) per 100 psoriasis patients. The following baseline variables were associated with the development of PsA in multivariate analysis: severe psoriasis (RR 5.4, P = 0.006), low level of education (university/college versus high school incomplete RR 0.22, P = 0.005; high school graduate versus high school incomplete RR 0.30, P = 0.049), and use of retinoid medications (RR 3.4, P = 0.02). In multivariate models with time-dependent variables, psoriatic nail pitting (RR 2.5, P = 0.002) and uveitis (RR 31.5, P = 0.0002) were associated with the development of PsA. Conclusion The incidence of PsA in patients with psoriasis is higher than previously reported. A severe psoriasis phenotype, presence of nail pitting, low level of education, and uveitis are predictive of the development of PsA in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Objectives. To compare obesity among individuals with PsA, psoriasis (PsO), RA and the general population (n), and identify correlates of obesity among individuals with PsO and PsA.Methods. We compared the BMI of patients with PsA (n = 644), PsO (n = 448), RA (n = 350) and the general population using age- and sex-adjusted linear and logistic regression analyses. We conducted multivariate analyses limited to PsO and PsA to determine correlates of BMI and obesity.Results. The mean BMI (kilogram per square metre) for individuals with PsA, PsO, RA and the general population were 29.6, 27.9, 27.3 and 26.1, respectively. The proportion with obesity was 37, 29, 27 and 18% for individuals with PsA, PsO, RA and the general population, respectively. The differences in BMI were significant between all categories (P < 0.05) except between PsO and RA. Age- and sex-adjusted linear and logistic regression confirmed that these differences were significant. In multivariate logistic regression analyses adjusted for age, sex, smoking, PsO duration, psoriasis area severity index score, use of DMARDs, glucocorticoids and biologics, the odds of obesity were 61% higher for PsA patients than PsO patients (95% CI 1.10, 2.37). When we additionally adjusted for the physical component summary of the short form-36, the association was attenuated and became insignificant.Conclusions. Individuals with PsA have a higher mean BMI than those with PsO, RA or the general population. The BMI difference between PsA and PsO correlates with physical health. [ABSTRACT FROM PUBLISHER]

Objective: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA., Methods: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies., Results: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East., Conclusion: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment., (Copyright © 2024 by the Journal of Rheumatology.)

The 2014 Update of the Canadian treatment recommendations for the management of spondyloarthritis recommended that patients at risk of peripheral spondyloarthritis, including patients with psoriatic arthritis (PsA), be assessed by a rheumatologist within 6 weeks of referral. This study aimed to: (1) investigate the proportion of PsA patients who were assessed by a rheumatologist within 6 weeks of referral to the PsA Clinic at Toronto Western Hospital and (2) investigate the possible reasons for delays for consult with a rheumatologist. We identified patients with PsA who were seen by rheumatologists at the PsA Clinic between January 2013 and May 2019. We used retrospective chart reviews of medical records and referral letters to determine the number of days between referral and assessment by a rheumatologist. The causes for delays were identified as no spots in the clinic or patient rescheduling their appointment due to their inability to attend the scheduled appointment. Among 168 patients, 43 (25.6%) patients met the recommendation. The median wait time was 78.5 days (IQR 83.5). The most common cause of delay was the lack of available spots in the PsA clinic. The majority of PsA patients at the TWH PsA Clinic were not seen within the wait-time recommendation. The most common factor that prevented a timely consultation with a rheumatologist was the lack of spots in the PsA clinic. Greater access to rheumatologists can improve the timely and effective care of PsA patients., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: Atherosclerotic vascular events (AVE) are a major cause of mortality and morbidity in systemic lupus erythematosus (SLE). We aimed to determine the effect of early recognition and therapy for both classic risk factors for AVE and for SLE, on the burden of AVE in SLE in recent decades., Methods: Inception patients who entered the University of Toronto Lupus Clinic between 1975 and 1987 followed to 1992 (Cohort 1), and between 1999 and 2011 followed to 2016 (Cohort 2) were studied. AVE attributed to atherosclerosis and occurring during the 17 years were identified. SLE disease activity and therapy as well as hypertension, hypercholesterolemia, hyperglycemia, and smoking were assessed. Analysis included descriptive statistics on baseline characteristics, traditional risk factors over the followup, outcome rates by each 100 person-years (PY), Kaplan-Meier cumulative AVE curves, as well as competing risk Cox models adjusted by inverse probability weights., Results: Of the 234 patients in Cohort 1, 26 patients (11%) had an AVE compared with 10 of 262 patients (3.8%) in Cohort 2. The rate per 100 PY of followup was 1.8 in Cohort 1 and 0.44 in Cohort 2 (p < 0.0001). Better control of all risk factors and disease activity was achieved in Cohort 2. There was a reduction of 60% in the risk for AVE in Cohort 2., Conclusion: The incidence of AVE in SLE in the modern era has declined in large part owing to more effective management of classic coronary artery risk factors and of SLE.

Objective: Antimalarials (AM) are recommended for all systemic lupus erythematosus (SLE) patients without specific contraindications. Their main adverse effect is retinal damage; however, heart disease has been described in isolated cases. The aim of our study is to describe 8 patients with AM-induced cardiomyopathy (AMIC) in a defined SLE cohort., Methods: Patients attending the Toronto Lupus Clinic and diagnosed with definite (based on endomyocardial biopsy; EMB) and possible AMIC were included [based on cardiac magnetic resonance imaging (cMRI) and other investigations]., Results: Eight female patients (median age 62.5 yrs, disease duration 35 yrs, AM use duration 22 yrs) were diagnosed with AMIC in the past 2 years. Diagnosis was based on EMB in 3 (extensive cardiomyocyte vacuolation, intracytoplasmic myelinoid, and curvilinear bodies). In 4 patients, cMRI was highly suggestive of AMIC (ventricular hypertrophy and/or atrial enlargement and late gadolinium enhancement in a nonvascular pattern). Another patient was diagnosed with complete atrioventricular block, left ventricular and septal hypertrophy, along with concomitant ocular toxicity. All patients had abnormal cardiac troponin I (cTnI) and brain natriuretic peptide (BNP), whereas 7/8 also had chronically elevated creatine phosphokinase. During followup, 1 patient died from refractory heart failure. In the remaining patients, hypertrophy regression and a steady decrease of heart biomarkers were observed after AM cessation., Conclusion: Once considered extremely rare, AMIC seems to be underrecognized, probably because of the false attribution of heart failure or hypertrophy to other causes. Certain biomarkers (cTnI, BNP) and imaging findings may lead to early diagnosis and enhance survival.

Objective: To evaluate the diagnosis, monitoring, and treatment of systemic lupus erythematosus (SLE) in Canada., Methods: A 63-question electronic survey was developed with the Canadian Rheumatology Association and others. Descriptive analyses of responses were performed., Results: Survey respondents (n = 175) reported varying practices in the diagnosis, monitoring, and treatment of SLE. Performance of laboratory investigations for diagnosis and monitoring varied, with 78% of responders performing them at least every 6 months. Validated measures of SLE disease activity and damage were not commonly used. Most common first-line agents besides steroids for induction therapy for class III or IV lupus nephritis included intravenous cyclophosphamide and mycophenolate mofetil. Antimalarial use was common, with 96% of respondents using these in active skin disease. Over 60% of respondents indicated that 80-100% of their patients were taking antimalarials, while another 25% indicated they used these drugs in up to 80% of their patients. There were 71% of responders who reported completing frequent (6-12 mos) ophthalmology screening in patients taking antimalarials. Biologics were infrequently used. Responders were more likely to stop azathioprine and chloroquine than hydroxychloroquine in pregnant patients with SLE. Other aspects of routine care including vaccination and cardiovascular risk management varied considerably. The majority (80%) agreed that a dedicated multidisciplinary care team would improve SLE care., Conclusion: Considerable practice variation in SLE management was noted. This may help inform future recommendations for the diagnosis, monitoring, and treatment of SLE in Canada.

Objective: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada., Methods: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online., Results: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination., Conclusion: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Objective: We aimed to estimate the proportion of underdiagnosis and undertreatment of cardiovascular risk factors (CVRF) in an international multicenter cohort of patients with psoriasis and psoriatic arthritis (PsA)., Methods: A cross-sectional analysis was conducted of patients with psoriatic disease from the International Psoriasis and Arthritis Research Team cohort. The presence of modifiable CVRF [diabetes, hypertension (HTN), dyslipidemia, smoking, elevated body mass index, and central obesity] and the use of appropriate therapies for HTN and dyslipidemia were determined. The 10-year CV risk was calculated according to the Framingham Risk Score. Physician adherence with guidelines for the treatment of dyslipidemia and HTN was assessed. Regression analysis was used to assess predictors of undertreatment of HTN and dyslipidemia., Results: A total of 2254 patients (58.9% PsA, 41.1% psoriasis) from 8 centers in Canada, the United States, and Israel were included. Their mean age was 52 ± 13.8 years and 53% were men. Of the patients, 87.6% had at least 1 modifiable CVRF, 45.1% had HTN, 49.4% dyslipidemia, 13.3% diabetes, 75.3% were overweight or obese, 54.3% central obesity, and 17.3% were current smokers. We found 59.2% of patients with HTN and 65.6% of patients with dyslipidemia were undertreated. Undertreatment was associated with younger age (≤ 50 yrs), having psoriasis, and male sex., Conclusion: In real-world settings, a large proportion of patients with psoriasis and PsA were underdiagnosed and undertreated for HTN and dyslipidemia. Strategies to improve the management of CVRF in psoriatic patients are warranted.

Objective: To assess the effect of tumor necrosis factor inhibitors (TNFi) on subclinical cardiovascular disease in patients with psoriatic disease., Methods: We performed a 2-stage study. In stage 1, carotid total plaque area was assessed in patients with psoriasis or psoriatic arthritis (PsA) (n = 319) by ultrasound at baseline and after 2-3 years. The annual progression rate of atherosclerosis was the outcome of interest. In stage 2, PsA patients receiving TNFi (n = 21) and age- and sex-matched PsA patients not receiving any biologic agent (n = 13) underwent 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography at baseline and 1 year to assess vascular inflammation, measured as target-to-background ratio (TBR). In both stages, multivariable regression analyses adjusted for cardiovascular risk factors and use of statins were performed., Results: In stage 1, men had significantly higher atherosclerosis progression than women (P < 0.001). TNFi was associated with reduced atherosclerosis progression in men after controlling for cardiovascular risk and use of statins (adjusted β = -2.20 [95% confidence interval -3.41, -1.00], P < 0.001). There was no association between TNFi and atherosclerosis progression in women (P = 0.74). In stage 2, patients receiving TNFi had reduced TBR at 1 year (P = 0.03). Those not receiving TNFi had no significant change in TBR (P = 0.32). The improvement in aortic vascular inflammation in the TNFi group was independent of cardiovascular risk factors (adjusted β = -0.41 [95% confidence interval -0.74, -0.08], P = 0.02)., Conclusion: Our findings indicate that TNFi treatment is associated with reduced progression of carotid plaques in men and improvement in vascular inflammation in both men and women with psoriatic disease., (© 2017, American College of Rheumatology.)

Objective: The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective., Methods: A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150 mg and 300 mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses., Results: Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses indicated the results were most sensitive to variation in PsARC response rates, change in HAQ, and utility values in both populations., Conclusions: Secukinumab is either dominant or cost-effective vs all licensed biologics for the treatment of active PsA in biologic-naive and biologic-experienced populations in Canada.

Objective: The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA)., Methods: A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference., Results: Recommendations for the management of SpA were created. Part II: Specific Management Recommendations addresses management with nonpharmacologic methods, nonsteroidal anti-inflammatories and analgesics, disease-modifying antirheumatic drugs, antibiotics, tumor necrosis factor inhibitors, other biologic agents, and surgery. Also included are 10 modifications for application to juvenile SpA., Conclusion: These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that implementation of these recommendations will promote best practices in the treatment of SpA.

Objective: The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA)., Methods: A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference. A survey was sent to the membership of the CRA to obtain an extended review that was used to finalize the recommendations., Results: Guidelines for the management of SpA were created. Part I focuses on the principles of management of SpA in Canada and includes 6 general management principles, 5 ethical considerations, target groups for treatment recommendations, 2 wait time recommendations, and recommendations for disease monitoring. Also included are 6 modifications for application to juvenile SpA., Conclusion: These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that the implementation of these recommendations will promote best practices in the treatment of SpA.

A biosimilar is intended to be highly similar to a reference biologic such that any differences in quality attributes (i.e., molecular characteristics) do not affect safety or efficacy. Achieving this benchmark for biologics, especially large glycoproteins such as monoclonal antibodies, is challenging given their complex structure and manufacturing. Regulatory guidance on biosimilars issued by the U.S. Food and Drug Administration, Health Canada and European Medicines Agency indicates that, in addition to a demonstration of a high degree of similarity in quality attributes, a reduced number of nonclinical and clinical comparative studies can be sufficient for approval. Following a tiered approach, clinical studies are required to address concerns about possible clinically significant differences that remain after laboratory and nonclinical evaluations. Consequently, a critical question arises: can clinical studies that satisfy concerns regarding safety and efficacy in one condition support "indication extrapolation" to other conditions? This question will be addressed by reviewing the case of a biosimilar to infliximab that was approved recently in South Korea, Europe, and Canada for multiple indications through extrapolation. The principles discussed should also apply to biosimilars of other monoclonal antibodies that are approved to treat multiple distinct conditions., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe the spatial distribution of incident cases of systemic lupus erythematosus (SLE) using geographic information systems (GIS)., Methods: Spatial analyses were carried out on 890 SLE patients and 541 psoriatic arthritis (PsA) patients (controls). Age- and sex-adjusted rates for SLE/PsA for each census tract were calculated using denominator population values from the Canadian census. Spatial variations in relative risk were estimated by modeling risk as the product of a time effect, an age effect, and a spatially autocorrelated risk surface to identify hot spots. Patients within the detected hot spot were compared to those outside the hot spot to identify explanatory factors., Results: SLE patients were predominantly female (87.75%) and the incidence rate was highest among those 15-19 years of age (2.4 cases/100,000 person-years). In an SLE hot spot containing 59 patients, 100% of the patients were female and 49.1% (n = 29) were Caucasian, while outside of the hot spot, 86.9% (n = 722) of the patients were female and 68.4% (n = 568) were Caucasian. The proportion of cases of Chinese ethnicity was significantly greater within the hot spot. An interaction was found between Chinese ethnicity and residence within the hot spot, with the risk of SLE to the Chinese population found to be twice the risk to the non-Chinese population., Conclusion: GIS was used to map SLE cases and a hot spot was identified after adjustment for age and sex. Ethnicity by itself did not confer an increased risk of SLE, but the interaction of ethnicity with location of residence significantly increased the risk of SLE., (Copyright © 2013 by the American College of Rheumatology.)

Objective: We aimed to determine disease severity and treatment of patients with psoriatic arthritis (PsA) in rheumatology practices in Canada through the PsA Assessment in Rheumatology (PAIR) study., Methods: Rheumatologists who were members of the Canadian Rheumatology Association were asked to complete a form for each patient addressing demographic questions, history, clinical examination, and patient-reported outcomes. Results were compared with a cohort seen in a PsA clinic during the same period., Results: From across Canada, 22 rheumatologists from 5 provinces submitted information about 233 consecutive patients with PsA [145 men (62.2%), 88 women (37.8%), mean age 53.2 yrs (±12.7), 88.4% disease duration>2 yrs]. A majority (80.7%) fulfilled ClASsification for Psoriatic ARthritis (CASPAR) criteria, and 30% had taken no disease-modifying antirheumatic drugs. Clinical joint damage was documented in 60% of the patients, active skin disease in 70%, and nail lesions in 32%. Only 22% were rated as having moderate to high disease activity, while 52% were rated as low disease activity and 26% were deemed in remission. The decision was based on joint counts, patient global assessment, physician global assessment, and acute-phase reactants. Twenty-seven percent of the patients were to have their medications changed based on the current visit, the majority for inadequate response to medications. Patients in the PAIR cohort had more inflamed joints but similar damage to those in the PsA clinic., Conclusion: Patients with PsA seen in regular rheumatology practice fulfill CASPAR criteria, have active disease, and more than half have joint damage. The majority have low activity or are in remission.

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease affecting up to 30% of psoriasis vulgaris (PsV) cases and approximately 0.25 to 1% of the general population. To identify common susceptibility loci, we performed a meta-analysis of three imputed genome-wide association studies (GWAS) on psoriasis, stratified for PsA. A total of 1,160,703 single-nucleotide polymorphisms (SNPs) were analyzed in the discovery set consisting of 535 PsA cases and 3,432 controls from Germany, the United States, and Canada. We followed up two SNPs in 1,931 PsA cases and 6,785 controls comprising six independent replication panels from Germany, Estonia, the United States, and Canada. In the combined analysis, a genome-wide significant association was detected at 2p16 near the REL locus encoding c-Rel (rs13017599, P=1.18 × 10(-8), odds ratio (OR)=1.27, 95% confidence interval (CI)=1.18-1.35). The rs13017599 polymorphism is known to associate with rheumatoid arthritis (RA), and another SNP near REL (rs702873) was recently implicated in PsV susceptibility. However, conditional analysis indicated that rs13017599, rather than rs702873, accounts for the PsA association at REL. We hypothesize that c-Rel, as a member of the Rel/NF-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3, and NFκBIA.

The Spondyloarthritis Research Consortium of Cananda (SPARCC) is a transdiscliplinary research network of investigators interested in spondyloarthritis. The group has been supported by a new research initiative by The Arthritis Society. SPARCC aims to address the genetic basis of susceptibility of the disease and develop and validate clinical and imaging outcomes to assess disease activity and structural damage over time, the response to therapy, and the clinical burden of illness in terms of quality of life and disability. The first step was to develop a database that would allow ascertainment of phenotype for genetic studies, as well as accurate and detailed longitudinal information for disease expression and outcome studies. This article describes the SPARCC database and outlines difficulties and possible solutions for maintaining such a database.

Objective: To describe the longterm effectiveness and safety of etanercept in Canadian patients with psoriatic arthritis (PsA), treated over 24 months in clinical practice., Methods: Patients with active PsA (≥ 3 tender and ≥ 3 swollen joints) were recruited from 22 centers. Etanercept was administered at 50 mg/week subcutaneously. In addition to clinical assessment of skin and joint disease, conducted at baseline and at Months 6, 12, 18, and 24, regular patient interviews were conducted by telephone. Patient responses related to health status, disability, and work productivity were scored using the patient global assessment tool, the Health Assessment Questionnaire (HAQ), the Health and Labour Questionnaire (HLQ), and the Fatigue Severity Scale., Results: Out of 110 patients, 71 (65%) maintained etanercept treatment through the end of our study. All clinical measures of disease severity, including joint tenderness/pain, joint swelling, and Psoriasis Area and Severity Index score, improved significantly between baseline and Month 6 of etanercept treatment and remained constant thereafter. By the end of our study, 79% of patients achieved a Psoriatic Arthritis Response Criteria response, and 56% of patients achieved a 0.5-point improvement on HAQ, indicating clinically significant improvement in disability; 14% of patients finished our study free of disability (HAQ = 0). Patients' work productivity and fatigue improved significantly in parallel with these clinical and functional improvements., Conclusion: Continuous treatment with etanercept over 2 years in a clinical setting improved clinical symptoms of PsA while reducing fatigue, improving work productivity, and ameliorating or eliminating disability.

The Toronto Psoriatic Arthritis Screening questionnaire (ToPAS) was developed as a tool to screen for psoriatic arthritis (PsA) in patients with psoriasis as well as in the general population. Thus, it differs from PsA-specific screening tools and may be used to screen for PsA in epidemiologic and family investigations. In a presentation at the 2009 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) in Stockholm, Sweden, the authors described the development, testing, and validation of the ToPAS tool. Results of a comparison of the ToPAS questionnaire with the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire were also presented. Modification and further validation of the ToPAS are under way.

Objective: To evaluate factors affecting therapeutic approaches used in clinical practice for the management of systemic lupus erythematosus (SLE), in a multicenter cohort., Methods: We combined data from 10 clinical adult SLE cohort registries in Canada. We used multivariate generalized estimating equation methods to model dichotomized outcomes, running separate regressions where the outcome was current exposure of the patient to specific medications. Potential predictors of medication use included demographic (baseline age, sex, residence, race/ethnicity) and clinical factors (disease duration, time-dependent damage index scores, and adjusted mean SLE Disease Activity Index-2K scores). The models also adjusted for clustering by center., Results: Higher disease activity and damage scores were each independent predictors of exposure to nonsteroid immunosuppressive agents, and for exposure to prednisone. This was not definitely demonstrated for antimalarial agents. Older age at diagnosis was independently and inversely associated with exposure to any of the agents studied (immunosuppressive agents, prednisone, and antimalarial agents). An additional independent predictor of prednisone exposure was black race/ethnicity (adjusted RR 1.46, 95% CI 1.18, 1.81). For immunosuppressive exposure, an additional independent predictor was race/ethnicity, with greater exposure among Asians (RR 1.39, 95% CI 1.02, 1.89) and persons identifying themselves as First Nations/Inuit (2.09, 95% CI 1.43, 3.04) than among whites. All of these findings were reproduced when adjustment for disease activity was limited to renal involvement., Conclusion: Ours is the first portrayal of determinants of clinical practice patterns in SLE, and offers interesting real-world insights. Further work, including efforts to determine how differing clinical approaches may influence outcome, is in progress.

Observational cohorts have emerged as important resources to study course and prognosis of chronic disease, and also facilitate phenotype definition for genetic studies. We describe the development and accomplishments of the PsA cohort at the University of Toronto as an example of an observational cohort that has allowed the description of disease manifestations, course and prognosis of PsA. We also describe the development of an international collaboration based on this cohort, which will further be used to study the incidence, prevalence and predictive factors for the development of PsA among patients with psoriasis.

Objective: To evaluate the effectiveness and safety of adalimumab in patients with active psoriatic arthritis (PsA) and an inadequate response to prior therapy., Methods: Patients were treated with subcutaneous injections of adalimumab 40 mg every other week in addition to their standard antirheumatic therapies in a 12-week, open-label study. Effectiveness evaluations at Week 12 included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) response rates, Psoriatic Arthritis Response Criteria (PsARC), active dactylitis, enthesitis, and target lesion assessment. Physical function was evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI)., Results: A total of 127 patients were enrolled. At Week 12, patients achieved ACR20, ACR50, and ACR70 response rates of 78.0%, 55.9%, and 21.3%, respectively. PASI50 and PASI75 response rates were 64.7% and 47.1%. A PsARC response was experienced by 70.1% of patients. Between baseline and Week 12, clinically and statistically significant reductions occurred in the mean total plaque score of the target lesion as well as in the percentages of patients with active dactylitis and enthesitis. A mean improvement in HAQ-DI was also observed (-0.44; p < 0.001). Three serious adverse events were reported, but none was considered related to adalimumab therapy., Conclusion: Adalimumab-treated patients achieved significant improvements in both skin and joint manifestations of PsA, as well as in physical function. Adalimumab was well tolerated and had a safety profile similar to that observed in other clinical trials of adalimumab for the treatment of PsA. ClinicalTrials.gov identifier: NCT00427362.

Objective: Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort., Methods: We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression., Results: In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (+/- SD) was 46.8 +/- 13.5 years, and disease duration at study entry was 12.1 +/- 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p

Patients with systemic lupus erythematosus (SLE) have a significantly increased risk of atherosclerotic coronary events. Traditional risk factors, such as hypertension and hypercholesterolemia, only partly account for the increased risk of coronary disease in SLE. Other important risk factors include disease and treatment-related factors. Novel markers of coronary risk in SLE are being investigated. Several methods have been used to detect subclinical atherosclerosis in patients with SLE. Among these, scintigraphic myocardial perfusion defects have been shown to be predictive of subsequent coronary events, independent of traditional Framingham risk factors. Although the aggressive treatment of reversible risk factors, such as lipids and blood pressure, is advocated by many, no published studies have yet demonstrated a clear reduction in risk of coronary events with this approach. Elucidation of risk factors and preventive strategies for accelerated atherosclerosis in SLE is the subject of ongoing research.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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.

Objective: A recent genome-wide pooling study noted a significant association of interleukin 23 receptor (IL-23R) and psoriasis. Overxpression of IL-23 has been detected in lesional psoriatic skin, and induces epidermal proliferation. Given the interplay between psoriasis and PsA, we examined the association of IL-23R variants in 2 independent Canadian Caucasian cohorts of patients with psoriatic arthritis (PsA)., Methods: We examined 496 PsA probands and 476 controls. Cases and controls were genotyped for a panel of 11 single-nucleotide polymorphisms (SNP) in IL-23R. Allele and haplotype associations were calculated using WHAP software. P values for haplotype associations were calculated using a permutation test., Results: The 381Gln allele of the coding SNP Arg381Gln (rs11209026) was found to be protective in the Canadian population (p=0.004; corrected p=0.044). A 2-marker haplotype from SNP rs7530511 and rs11209026 was associated with PsA (p=0.011). All 3-marker sliding windows containing SNP rs11209026 were associated with PsA (p=0.02 for all 3 windows). The magnitude of effect of IL-23R association in PsA appears to be similar to that reported in uncomplicated psoriasis., Conclusion: Significant associations between Arg381Gln SNP and haplotypes encoding this variant were noted in PsA. It remains to be determined what contribution of this association, if any, is specifically due to the inflammatory arthritis (PsA) rather than psoriasis.

Objective: Recent studies have shown that a nonsynonymous single-nucleotide polymorphism (SNP) (Arg381Gln; rs11209026) in the interleukin-23 receptor (IL-23R) gene on chromosome 1p31 is associated with Crohn's disease and psoriasis. Given the clinical and immunologic overlap between ankylosing spondylitis (AS) and these diseases, and the potential function of this candidate SNP, this study was undertaken to examine the association of IL-23R variants with AS in multiple Canadian populations., Methods: We examined 3 cohorts of AS patients from established rheumatic disease centers in Canada. The majority of AS patients were Caucasians of northern European descent, and all patients satisfied the modified New York classification criteria for AS or for juvenile spondylarthritis. We examined 424 AS probands and 401 controls from Alberta, 251 AS probands and 122 controls from Toronto, and 121 AS probands and 219 controls from Newfoundland. Ten IL-23R SNPs were genotyped, 9 of which were incorporated in the haplotype analysis. Allele and haplotype associations were calculated using the WHAP software package. P values for haplotype associations were calculated using a permutation test., Results: The primary SNP of interest in a previous study of inflammatory bowel disease (IBD) (Arg381Gln; rs11209026) was found to be protective against AS in the Newfoundland population (P=0.04) and in the Toronto population (P=0.04) in single-marker univariate analysis. The strongest association, however, was with SNP rs11465804 (P=0.007 for the Newfoundland population and P=0.0007 for the Toronto population). A 3-marker sliding window omnibus test revealed a significant association with markers rs10489629, rs2201841, and rs11465804 in both the Newfoundland population (P=0.04) and the Alberta population (P=0.034). Our results were independent of the IBD and psoriasis status of the AS patients., Conclusion: This concurrent analysis of 3 distinct AS populations and their regional controls demonstrates a disease association with the IL-23R locus and implicates the same polymorphisms associated with IBD and psoriasis.

Objective: To determine whether there has been a change in mortality rates over the last 3 decades in patients with psoriatic arthritis (PsA) whose cases were followed prospectively., Methods: Patients receiving followup care according to a standard protocol at the University of Toronto PsA Clinic between 1978 and 2004 were included. Information on patient deaths was collected prospectively. Mortality data for the general population of Ontario, Canada, stratified by 5-year age bands, sex, and calendar year from 1978 to 2004, were used to calculate the reference rates. Standardized mortality ratios (SMRs) were calculated through use of Poisson regression models for the number of observed deaths. Time trend analyses were performed through the use of 10-year "rolling-average" SMRs and followup period-specific SMRs stratified by the period of entry into clinic., Results: Of 680 patients with PsA, 106 (15.6%) (55 women and 51 men) have died. Major causes of death were disease of the circulatory system, neoplasms, diseases of the respiratory system, diseases of the gastrointestinal system, injuries/poisoning, and unknown. The overall SMR for the period 1978-2004 was 1.36 (95% confidence interval 1.12, 1.64). The estimated number of life-years lost by the PsA patient cohort overall was 2.99 years (95% confidence interval 1.14, 4.77). For patients who entered the cohort during the years 1978-1986, the SMRs were 1.89, 1.83, and 1.21 for followup periods 1978-1986, 1987-1995, and 1996-2004, respectively. For patients who entered the cohort during the years 1987-1995, the SMRs were 0.55 and 0.82, while the SMR for those who entered during 1996-2004 was 0.56., Conclusion: The drop in SMRs in this PsA clinic population suggests that the mortality risk has improved over time. This improved survival may reflect disease severity at presentation in the earlier cohort as well as earlier diagnosis and more aggressive treatment in the more recent followup period.

Rheumatological disorders are complex conditions characterized by a variety of clinical manifestations and courses in different patients with the same condition. The best way to understand the course and prognosis of these patients is through longitudinal observational cohort studies. Such studies have been facilitated by computer technology that allows tracking of large numbers of patients and visits and analysis of a large amount of data. There are requirements for such datasets to be informative: internal and external consistency; clearly defined methods of observation and measurement; complete followup; consideration of potential confounders. We describe the usefulness of an observational cohort analysis using the University of Toronto Psoriatic Arthritis Clinic Database as a model. Analysis issues are highlighted and proposed mechanisms offered for keeping patients involved to ensure complete followup is maintained.

Objectives: To evaluate whether rheumatologists experienced in psoriatic arthritis (PsA) assess peripheral and axial involvement in the same way and to consider core clinical measurements that should be included in clinical trials in PsA., Methods: Ten patients with PsA, representing a broad range of joint inflammation, joint damage, and spinal involvement, were selected for the study. Each patient was examined by each of 10 rheumatologists, members of the Spondyloarthritis Research Consortium of Canada, according to a Latin Square design. Assessments included scoring actively inflamed joints and damaged joints, dactylitis, enthesitis, and spinal measurements. Variance components analyses were conducted for continuous measurements based on models with observer, patient, and order effects. Estimates of intraclass correlation coefficients and associated 95% confidence intervals were obtained., Results: There was substantial reliability in the assessment of the number of actively inflamed joints and excellent agreement in the number of damaged joints. Only moderate agreement was found for the number of digits with dactylitis. There was excellent agreement among observers in the intermalleolar distance measurements, but there was not as good agreement in the other measurements of spinal mobility. There was good agreement among the observers in detecting plantar fasciitis, however, the other entheses did not fare as well., Conclusion: In this first multicenter study of the assessment of clinical evaluation of patients with PsA we found that the assessment of peripheral joint disease is reliable although training should be performed prior to initiation of drug trials or comparative studies in this disease. The assessment of back measurements in PsA and other spondyloarthritis requires further study.