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Objective: We aimed to assess the association between antimalarial adherence and cardiovascular events between incident rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) population‐based cohorts. Methods: All patients with incident RA/SLE and incident antimalarial use in British Columbia, Canada, between January 1997 and March 2015 were identified using provincial administrative databases. The outcomes were incident cardiovascular events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). The exposure was antimalarial adherence with levels: discontinuation (proportion of days covered [PDC = 0]), nonadherence (0 < PDC < 0.90), and adherence (PDC ≥ 0.90). We used marginal structural models to estimate the effect of antimalarial adherence on the rate of cardiovascular events, accounting for potential confounders. Results: We identified 16,538 individuals with incident RA/SLE and incident antimalarial use without any cardiovascular event before the index date. Over nine years mean follow‐up, 2,174 incident cardiovascular events (13.2%) were observed. The adjusted hazard ratio (aHR) for incident cardiovascular events for antimalarial adherence relative to discontinuation was 0.72 (95% confidence interval [CI] 0.64–0.81) and 1.01 (95% CI 0.90–1.14) for nonadherence. Additionally, the aHRs for all cardiovascular events, MI, stroke, and VTE for adherence relative to nonadherence was 0.71 (95% CI 0.61–0.82), 0.62 (95% CI 0.51–0.75), 0.45 (95% CI 0.36–0.58), and 0.65 (95% CI 0.46–0.93), respectively. We found older age modified the association between antimalarial adherence and cardiovascular events (P = 0.02). Conclusion: When people newly diagnosed with RA or SLE take their antimalarial regularly as prescribed (PDC ≥ 0.90), they have a 29% lower risk of sustaining a cardiovascular event than patients with a lower degree of adherence (PDC < 0.90) and a 28% lower risk than if they discontinue antimalarials. [ABSTRACT FROM AUTHOR]

Objective: We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID‐19 outcomes in a population‐based cohort study. Methods: Participants were 18 years or older, tested positive for SARS‐CoV‐2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS‐CoV‐2 test included conventional disease‐modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non‐TNFi biologics or targeted synthetic disease‐modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID‐19 outcomes were hospitalizations for COVID‐19, ICU admissions, and deaths within 60 days of a positive test. Exposure score–overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID‐19 outcomes. Results: From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non‐TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID‐19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81‐4.40], all immunosuppressants: 2.08 [1.51‐2.87], and glucocorticoids: 1.63 [1.36‐1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34‐4.74], immunosuppressants: 2.88 [1.73‐4.78], and glucocorticoids: 1.86 [1.37‐2.54]. Only glucocorticoids use was associated with a significant increase in 60‐day mortality: 1.58 [1.21‐2.06]. No other IIAs displayed statistically significant associations with severe COVID‐19 outcomes. Conclusion: Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID‐19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs. [ABSTRACT FROM AUTHOR]

Objectives To determine the impact of the introduction of biologic DMARDs (bDMARDs) on severe infections among people newly diagnosed with RA compared with non-RA individuals. Methods In this population-based retrospective cohort study using administrative data (from 1990–2015) for British Columbia, Canada, all incident RA patients diagnosed between 1995 and 2007 were identified. General population controls with no inflammatory arthritis were matched to RA patients based on age and gender, and were assigned the diagnosis date (i.e. index date) of the RA patients they were matched with. RA/controls were then divided into quarterly cohorts according to their index dates. The outcome of interest was all severe infections necessitating hospitalization or occurring during hospitalization after the index date. We calculated 8-year severe infection rates for each cohort and conducted interrupted time-series analyses to compare severe infection trends in RA/controls with index date during pre-bDMARDs (1995–2001) and post-bDMARDs (2003–2007) periods. Results A total of 60 226 and 588 499 incident RA/controls were identified. We identified 14 245 severe infections in RA, and 79 819 severe infections in controls. The 8-year severe infection rates decreased among RA/controls with increasing calendar year of index date in the pre-bDMARDs period, but increased over time only among RA, not controls, with index date in the post-bDMARDs period. The adjusted difference between the pre- and post-bDMARDs secular trends in 8-year severe infection rates was 1.85 (P  = 0.001) in RA and 0.12 (P  = 0.29) in non-RA. Conclusion RA onset after bDMARDs introduction was associated with an elevated severe infection risk in RA patients compared with matched non-RA individuals. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the potential temporal association between hydroxychloroquine (HCQ) use and cardiovascular (CV) events among patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Methods: We conducted a nested case–control study within inception cohorts of SLE and RA patients using administrative health databases including the entire population of British Columbia, Canada. We identified cases with incident CV events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). We matched each case with up to 3 controls on age, sex, and rheumatic disease. HCQ exposure was categorized by the time between the last HCQ prescription date covered and the index date as current use, recent use, remote use, or never used. We used conditional logistic regression to assess the association between HCQ exposure and CV events, using remote use as the reference group. Results: We identified 10,268 cases and 29,969 controls. Adjusted conditional odd ratios (cORs) and 95% confidence intervals (95% CIs) for current HCQ use relative to remote use were 0.86 (0.77–0.97) for combined CV events, 0.88 (0.74–1.05) for MI, 0.87 (0.74–1.03) for stroke, and 0.74 (0.59–0.94) for VTE. Recent HCQ users and nonusers had similar odds of combined CV events as remote users (cORs 0.93, 95% CI 0.77–1.13 and 0.96, 95% CI 0.88–1.04, respectively). Conclusion: In this nested case–control study of patients with SLE and RA, we found a reduced risk of overall CV events associated with current HCQ use, including reductions in VTE and trends toward reductions in MI and stroke. These findings suggest a possible cardiovascular preventative benefit of HCQ use. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE). Methods: All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow‐up. We used cause‐specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes. Results: We identified 11,518 propensity score–matched patients with RA or SLE in each group. Over the mean follow‐up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause‐specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89–1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83–1.04), 0.98 (95% CI 0.87–1.11), and 0.95 (95% CI 0.84–1.07), respectively. Conclusion: Risk of any type of arrhythmia was not increased among new users of HCQ. [ABSTRACT FROM AUTHOR]

Objective: Bone marrow lesions (BMLs) are associated with painful and progressive osteoarthritis (OA). Quantitative magnetic resonance imaging (MRI) has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) relaxation values (T1Gd) in hips with BML to hips without BML in a population‐based study. Reduced T1Gd suggests depleted glycosaminoglycan. Our hypothesis was that mean T1Gd is lower in hips with BML compared to hips without BML. Methods: Study participants (n = 128) were recruited from a cross‐sectional population‐based study of people ages 20–49 years with and without hip pain. dGEMRIC and proton density (PD)–weighted MRI scans of 1 hip from each participant were used for this analysis. BMLs were identified from PD‐weighted fat‐suppressed images. We applied a sampling‐weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T1Gd (significance: P < 0.05). The model was adjusted for age, sex, body mass index (BMI), hip pain, cam/pincer deformity, and physical activity. Results: Thirty‐two (25%) of the 128 participants had at least 1 BML. Subjects with at least 1 BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T1Gd was 75.25 msec lower (95% confidence interval –149.69, –0.81; P = 0.048) (9%) in the BML compared to the no‐BML group. Conclusion: Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to assess adherence to system‐level performance measures measuring retention in rheumatology care and disease modifying anti‐rheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Methods: We used a validated health administrative data case definition to identify individuals with RA in Ontario, Canada, between 2002 and 2014 who had at least 5 years of potential follow‐up prior to 2019. During the first 5 years following diagnosis, we assessed whether patients were seen by a rheumatologist yearly and the proportion dispensed a DMARD yearly (in those aged ≥66 for whom medication data were available). Multivariable logistic regression analyses were used to estimate the odds of remaining under rheumatologist care. Results: The cohort included 50,883 patients with RA (26.1% aged 66 years and older). Over half (57.7%) saw a rheumatologist yearly in all 5 years of follow‐up. Sharp declines in the percentage of patients with an annual visit were observed in each subsequent year after diagnosis, although a linear trend to improved retention in rheumatology care was seen over the study period (P < 0.0001). For individuals aged 66 years or older (n = 13,293), 82.1% under rheumatologist care during all 5 years after diagnosis were dispensed a DMARD annually compared with 31.0% of those not retained under rheumatology care. Older age, male sex, lower socioeconomic status, higher comorbidity score, and having an older rheumatologist decreased the odds of remaining under rheumatology care. Conclusion: System‐level improvement initiatives should focus on maintaining ongoing access to rheumatology specialty care. Further investigation into causes of loss to rheumatology follow‐up is needed. [ABSTRACT FROM AUTHOR]

BackgroundPractice guidelines emphasize the use of exercise and weight reduction as the first line of management for knee osteoarthritis (OA). However, less than half of the people with mild OA participate in moderate intensity physical activity. Given that physical activities have been shown to reduce pain, improve quality of life, and have the potential to reduce the progression of joint damage, many people with OA are missing the benefits of this inexpensive intervention. ObjectiveThe objectives of this study are (1) to develop a behavioral theory-informed Internet intervention called Osteoarthritis Physical Activity & Exercise Net (OPEN) for people with previously undiagnosed knee OA, and (2) to assess the efficacy of the OPEN website for improving physical activity participation through a proof-of-concept study. MethodsOPEN was developed based on the theory of planned behavior. Efficacy of this online intervention is being assessed by an ongoing proof-of-concept, single-blind randomized controlled trial in British Columbia, Canada. We are currently recruiting participants and plan to recruit a total of 252 sedentary people with previously undiagnosed knee OA using a set of validated criteria. Half of the participants will be randomized to use OPEN and receive an OA education pamphlet. The other half only will receive the pamphlet. Participants will complete an online questionnaire at baseline, 3 months, and 6 months about their participation in physical activities, health-related quality of life, and motivational outcomes. In addition, we will perform an aerobic fitness test in a sub-sample of participants (n=20 per study arm). In the primary analysis, we will use logistic regression to compare the proportion of participants reporting being physically active at or above the recommended level in the 2 groups, adjusting for baseline measurement, age, and sex. ResultsThis study evaluates a theory-informed behavioral intervention at a time when people affected with OA tend to be more motivated to adopt an active lifestyle (ie, at the early stage of OA). Our approach, which consisted of the identification of early knee OA followed immediately by an online intervention that directly targets physical inactivity, can be easily implemented across communities. ConclusionsOur online intervention directly targets physical inactivity at a time when the joint damage tends to be mild. If OPEN is found to be effective in changing long-term physical activity behaviors, it opens further opportunities to promote early diagnosis and to implement lifestyle interventions. Trial RegistrationClinicaltrial.gov: NCT01608282; http://clinicaltrials.gov/ct2/show/NCT01608282 (Archived by WebCite at http://www.webcitation.org/6G7sBBayI)

Objectives To determine whether the introduction of biological DMARDs (bDMARDs) was associated with reduced incidences of total hip and knee arthroplasty (THA/TKA) among patients with RA compared with OA. Methods Using a population-based cohort in British Columbia, Canada, RA and OA patients diagnosed between 1995 and 2007 were divided into semi-annual cohorts according to diagnosis date. For each cohort, we calculated 8-year incidence rates of THA and TKA. We compared levels and trends of THA/TKA incidence in RA/OA patients diagnosed during pre-bDMARDs (1995–2001) and post-bDMARDs (2003–2007) periods using interrupted time-series analysis, adjusting for baseline characteristics. Adjusted 8-year total joint arthroplasty incidence estimated for RA/OA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends. Results We identified 60 227 RA and 288 260 OA incident cases. For cohorts diagnosed pre-bDMARDs, 8-year THA/TKA incidence rates increased over time in both RA and OA. For cohorts diagnosed post-bDMARDs, these rates decreased over time in RA but continued to increase for OA. For RA, differences between the post- and pre-bDMARDs secular trends in incidence rates were −0.49 (P  = 0.002) for THA and −0.36 (P  = 0.003) for TKA, compared with +0.40 (P  = 0.006) and +0.54 (P  < 0.001), respectively, for OA. For RA cohorts diagnosed five years after bDMARDs introduction, 8-year incidences were 26.9% and 12.6% lower for THA and TKA, respectively, than expected rates. In contrast, corresponding rates in OA were higher by 11.7% and 16.6%, respectively. Conclusion Arthritis onset after bDMARDs introduction is associated with a significant reduction in THA/TKA incidence in RA, but not in OA. The reduction reflects a significant improvement in RA treatment during the biological era. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common, chronic disease where health-related quality of life (HRQL) is one of the main goals of therapy. As such, instruments used to measure HRQL in RA must be able to discriminate across RA severity. The two basic categories of instruments used to measure HRQL are generic instruments and disease-specific instruments. Generic instruments can be further subdivided into preference-based measures which yield both single and multi-attribute utility values anchored at zero (death) and 1.00 (perfect health) as a measure of HRQL. The scores from these types of instruments can be integrated into cost-utility analyses as the weightings for quality adjusted life years. We assessed the construct validity of utility scores from four generic preference-based measures (the Health Utilities Index 2 and 3 (HUI2, HUI3), the EuroQol 5D (EQ-5D), and the Short Form 6-D (SF- 6D) and disease specific measures (the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and the Health Assessment Questionnaire (HAQ)) in a sample of 313 RA patients in British Columbia, Canada. We also estimated the minimally important differences (MID) for each of the measures. Generally, as anticipated, the disease-specific measures were better able to discriminate across groups with higher RA severity: however, utility scores from each of the scales also appeared to discriminate well across RA severity categories. The MID values agreed with those previously reported in the literature for the HUI2, SF-6D and the HAQ and provided new information for the HUI3, EQ-5D and the RAQoL. We conclude that the all of the preference-based utility measures that were evaluated appear to adequately discriminate across levels of RA severity. Keywords: Utility; Rheumatoid arthritis; Construct validity; Canada

Objectives: The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint replacement surgery, and prevention of OA by reducing obesity and overweight. Methods: We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons. Results: Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades). Conclusions: In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere. [ABSTRACT FROM AUTHOR]