When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

Comparative Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and Hospitalizations : A General Population Cohort Study.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) decrease serum urate levels, but whether this translates into prevention of recurrent flares among patients with gout and gout-primary emergency department (ED) visits or hospitalizations is unknown. OBJECTIVE: To compare gout flares and cardiovascular events among patients with gout initiating SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is), another second-line glucose-lowering agent not associated with serum urate levels or cardiovascular risk. DESIGN: Propensity score-matched, new-user cohort study. SETTING: General population database from 1 January 2014 to 30 June 2022. PARTICIPANTS: Patients with gout and type 2 diabetes. MEASUREMENTS: The primary outcome was recurrent gout flare counts ascertained by ED, hospitalization, outpatient, and medication dispensing records. Secondary outcomes included myocardial infarction and stroke; genital infection (positive control) and osteoarthritis encounter (negative control) were also assessed. Poisson and Cox proportional hazards regressions were used with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis). RESULTS: After propensity score matching, the flare rate was lower among SGLT2i initiators than DPP-4i initiators (52.4 and 79.7 events per 1000 person-years, respectively), with a rate ratio (RR) of 0.66 (95% CI, 0.57 to 0.75) and a rate difference (RD) of -27.4 (CI, -36.0 to -18.7) per 1000 person-years. The corresponding RR and RD for gout-primary ED visits and hospitalizations were 0.52 (CI, 0.32 to 0.84) and -3.4 (CI, -5.8 to -0.9) per 1000 person-years, respectively. The corresponding hazard ratio (HR) and RD for myocardial infarction were 0.69 (CI, 0.54 to 0.88) and -7.6 (CI, -12.4 to -2.8) per 1000 person-years; the HR for stroke was 0.81 (CI, 0.62 to 1.05). Those who initiated SGLT2is showed higher risk for genital infection (HR, 2.15 [CI, 1.39 to 3.30]) and no altered risk for osteoarthritis encounter (HR, 1.07 [CI, 0.95 to 1.20]). Results were similar when propensity score overlap weighting was applied. LIMITATION: Participants had concurrent type 2 diabetes. CONCLUSION: Among patients with gout, SGLT2is may reduce recurrent flares and gout-primary ED visits and hospitalizations and may provide cardiovascular benefits. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: a population-based interrupted time-series analysis.

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.

Has the incidence of total joint arthroplasty in rheumatoid arthritis decreased in the era of biologics use? A population-based cohort study.

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.

Increased risk of severe infections and mortality in patients with newly diagnosed systemic lupus erythematosus: a population-based study.

OBJECTIVE: To evaluate the risk of severe infection and infection-related mortality among patients with newly diagnosed SLE. METHODS: We conducted an age- and gender-matched cohort study of all patients with incident SLE between 1 January 1997 and 31 March 2015 using administrative health data from British Columbia, Canada. Primary outcome was the first severe infection after SLE onset necessitating hospitalization or occurring during hospitalization. Secondary outcomes were total number of severe infections and infection-related mortality. RESULTS: We identified 5169 SLE patients and matched them with 25 845 non-SLE individuals from the general population, yielding 955 and 1986 first severe infections during 48 367 and 260 712 person-years follow-up, respectively. The crude incidence rate ratios for first severe infection and infection-related mortality were 2.59 (95% CI: 2.39, 2.80) and 2.20 (95% CI: 1.76, 2.73), respectively. The corresponding adjusted hazard ratios were 1.82 (95% CI: 1.66, 1.99) and 1.61 (95% CI: 1.24, 2.08). SLE patients had an increased risk of a greater total number of severe infections with crude rate ratio of 3.24 (95% CI: 3.06, 3.43) and adjusted rate ratio of 2.07 (95% CI: 1.82, 2.36). CONCLUSION: SLE is associated with increased risks of first severe infection (1.8-fold), a greater total number of severe infections (2.1-fold) and infection-related mortality (1.6-fold).

Ten-year risk of cerebrovascular accidents in incident rheumatoid arthritis: a population-based study of trends over time.

OBJECTIVE: To evaluate secular trends in 10-year risk of incident cerebrovascular accidents (CVA), in incident RA relative to the general population. METHODS: We conducted a retrospective study of a population-based incident cohort with RA onset from 1997 to 2004 in British Columbia, Canada, with matched general population controls (2:1), using administrative health data. RA and general population cohorts were divided according to year of RA onset, defined according to the first RA visit of the case definition. Incident CVA was defined as the first CVA occurring within 10 years from the first RA visit. Secular trend was assessed using delayed-entry Cox models with a two-way interaction term between the year of RA onset and indicator of RA vs general population. Linear, quadratic and spline functions of year of RA onset were compared with assess non-linear effects. The model with the lowest Akaike Information Criterion was selected. RESULTS: Overall, 23 545 RA and 47 090 general population experienced 658 and 1220 incident CVAs, respectively. A spline Cox model with a knot at year of onset 1999 was selected. A significant decline in risk of CVA was observed in individuals with RA onset after 1999 [0.90 (0.86, 0.95); P = 0.0001]. The change in CVA risk over time differed significantly in RA with onset from 1999 onwards compared with the general population (P-value of interaction term = 0.03), but not before 1999 (P = 0.06). CONCLUSION: Our findings suggest that people with RA onset from 1999 onwards, had a significantly greater decline in 10-year risk of CVA compared with the general population.

Persistent premature mortality gap in dermatomyositis and polymyositis: a United Kingdom general population-based cohort study.

OBJECTIVE: DM and PM are associated with substantial morbidity and mortality. We aimed to examine recent trends. METHODS: Using The Health Improvement Network, we identified patients with incident DM/PM (defined by ≥1 Read diagnosis code) aged 18-89 years with ≥1 year of continuous enrolment prior to the cohort entry date and up to 10 comparators matched on age, sex and entry year. The cohort was divided in two based on the year of DM/PM diagnosis: the early cohort (1999-2006) and late cohort (2007-2014). We calculated multivariable hazard ratios (HR) for death using a Cox-proportional hazards model and multivariable rate differences (RD) using an additive hazard model. RESULTS: We identified 410 DM cases (mean age: 58 years, 66% female) and 407 PM cases (mean age: 59 years, 61% female). Both DM cohorts had excess mortality compared with the comparison cohorts (71.5 vs 12.9 deaths/1000 person-years [PY] in the early cohort and 49.1 vs 10.4 deaths/1000 PY in the late cohort). The multivariable HRs were 7.51 (95% CI: 4.20, 13.42) in the early cohort and 5.42 (95% CI: 3.11, 9.45) in the late cohort (P-value for interaction = 0.59), and multivariable RDs were 56.2 (95% CI: 31.8, 81.2) in the early cohort and 36.3 (95% CI: 19.6, 53.0) in the late cohort (P-value for interaction = 0.15). A similar trend existed in PM. CONCLUSION: The premature mortality gap in DM/PM has not considerably improved in recent years, highlighting an unmet need for therapeutic improvement.

The risk and trend of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a general population-based study.

OBJECTIVES: To estimate the overall risk of venous thromboembolism (VTE), pulmonary embolism (PE) and deep vein thrombosis (DVT) among patients newly diagnosed with RA compared with the general population without RA; and to estimate the risk trends of VTE, PE and DVT after RA diagnosis up to 5 years compared with the general population. METHODS: Using previously validated RA case definition, we conducted a matched cohort study using the population-based administrative health database from the province of British Columbia, Canada. We calculated incidence rates (IRs) and fully adjusted hazard ratios (HRs) for the risk of VTE, DVT and PE after RA index date. RESULTS: Among 39 142 incident RA patients (66% female, mean age 60), 1432, 543 and 1068 developed VTE, PE and DVT, respectively. IRs for the RA cohort were 3.79, 1.43 and 2.82 per 1000 person-years vs 2.70, 1.03 and 1.94 per 1000 person-years for the non-RA cohort. After adjusting for VTE risk factors, the HRs (95% CI) were 1.28 (1.20, 1.36), 1.25 (1.13, 1.39) and 1.30 (1.21, 1.40) for VTE, PE and DVT, respectively. The fully adjusted HRs for VTE during the first five years after RA diagnosis were 1.60, 1.47, 1.40, 1.30 and 1.28, respectively. A similar trend was shown in PE. CONCLUSION: This population-based study demonstrates that RA patients have an increased risk of VTE, PE and DVT after diagnosis compared with the general population. This risk is independent of traditional VTE risk factors and is highest during the first year after RA diagnosis, then progressively declined.

Past and Future Burden of Inflammatory Bowel Diseases Based on Modeling of Population-Based Data.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) exist worldwide, with high prevalence in North America. IBD is complex and costly, and its increasing prevalence places a greater stress on health care systems. We aimed to determine the past current, and future prevalences of IBD in Canada. METHODS: We performed a retrospective cohort study using population-based health administrative data from Alberta (2002-2015), British Columbia (1997-2014), Manitoba (1990-2013), Nova Scotia (1996-2009), Ontario (1999-2014), Quebec (2001-2008), and Saskatchewan (1998-2016). Autoregressive integrated moving average regression was applied, and prevalence, with 95% prediction intervals (PIs), was forecasted to 2030. Average annual percentage change, with 95% confidence intervals, was assessed with log binomial regression. RESULTS: In 2018, the prevalence of IBD in Canada was estimated at 725 per 100,000 (95% PI 716-735) and annual average percent change was estimated at 2.86% (95% confidence interval 2.80%-2.92%). The prevalence in 2030 was forecasted to be 981 per 100,000 (95% PI 963-999): 159 per 100,000 (95% PI 133-185) in children, 1118 per 100,000 (95% PI 1069-1168) in adults, and 1370 per 100,000 (95% PI 1312-1429) in the elderly. In 2018, 267,983 Canadians (95% PI 264,579-271,387) were estimated to be living with IBD, which was forecasted to increase to 402,853 (95% PI 395,466-410,240) by 2030. CONCLUSION: Forecasting prevalence will allow health policy makers to develop policy that is necessary to address the challenges faced by health systems in providing high-quality and cost-effective care.

Trends of venous thromboembolism risk before and after diagnosis of gout: a general population-based study.

OBJECTIVE: To estimate the overall risk and the temporal trend of venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE) before and after gout diagnosis in an incident gout cohort compared with the general population. METHODS: We conducted a matched cohort study using a province-wide population-based administrative health database in Canada. We calculated incidence rates (IRs) and multivariable adjusted hazard ratios (HRs) for the risk of VTE, DVT and PE before and after gout diagnosis. RESULTS: Among 130 708 incident individuals with gout (64% male, mean age 59 years), 2071 developed VTE, 1377 developed DVT and 1012 developed PE. IRs per 1000 person-years for gout were 2.63, 1.74 and 1.28 compared with 2.03, 1.28 and 1.06 for non-gout, respectively. The fully adjusted HRs (95% CI) for VTE, DVT and PE were 1.22 (1.13, 1.32), 1.28 (1.17, 1.41) and 1.16 (1.05, 1.29). For the pre-gout period, the fully adjusted HRs (95% CI) were 1.51 (1.38, 1.64), 1.55 (1.40, 1.72) and 1.47 (1.31, 1.66) for VTE, DVT and PE. During the third, second and first years preceding gout, the fully adjusted HRs for VTE were 1.44, 1.56 and 1.62. During the first, second, third, fourth and fifth years after gout, the fully adjusted HRs were 1.63, 1.29, 1.33, 1.28 and 1.22. Similar trends were also seen for DVT and PE. CONCLUSION: Increased risks of VTE, DVT and PE were found both before and after gout diagnosis. The risk increased gradually before gout, peaking in the year prior to diagnosis, and then progressively declined. Gout-associated inflammation may contribute to venous thrombosis risk.

Heart disease and the risk of allopurinol-associated severe cutaneous adverse reactions: a general population-based cohort study.

BACKGROUND: Allopurinol is commonly prescribed for gout, and its clinical use may expand with ongoing trials assessing its potential cardiorenal benefits. Because heart disease has been suggested to be a risk factor for allopurinol-associated severe cutaneous adverse reactions, we sought to confirm this association in a Canadian general population cohort. METHODS: We used population data from British Columbia, Canada, to identify all incident allopurinol users between 1997 and 2015. We examined the association between heart disease (ischemic heart disease and heart failure) and the risk of hospital admission for severe cutaneous adverse reactions, adjusting for known and purported risk factors. We also evaluated the joint effects of combined clinical and demographic risk factors. RESULTS: Among 130 325 allopurinol initiators, 109 hospital admissions occurred for allopurinol-associated severe cutaneous adverse reactions. The multivariable relative risk among those with heart disease was 1.55 (95% confidence interval 1.01-2.37). Patients with heart disease and chronic kidney disease who were started on an allopurinol dosage of greater than 100 mg/d had an 11-fold higher risk. Allopurinol initiation at a lower dosage among patients with heart disease and chronic kidney disease resulted in a fivefold reduction in risk. Older women with heart disease from regions with large Asian populations had a 23-fold higher risk of allopurinol-associated severe cutaneous adverse reactions than younger men without heart disease from other regions. INTERPRETATION: Heart disease is independently associated with risk of allopurinol-associated severe cutaneous adverse reactions, similar to chronic kidney disease, and low-dosage allopurinol initiation may substantially mitigate this risk. Risk factors for these rare but serious reactions should be considered when initiating allopurinol.

Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: a case-based review.

The objective of the study was to determine the clinical features and treatment course in Canadian patients with dermatomyositis (DM) associated with the anti-melanoma differentiation-associated gene 5 antibody (MDA5). A retrospective chart review of consecutive patients with anti-MDA5 antibody DM from two Canadian tertiary care centre between 2014 and 2018 was done. Twenty-one consecutive cases of anti-MDA5-positive DM were identified. Median age at diagnosis was 52 years, 71% Asians, predominantly Chinese, and 29% Caucasians. In this case series, all patients had either typical DM rash, or vasculopathy and ulceration unique to anti-MDA5-positive DM. 38% of the patients had rapid progressive (RP)-interstitial lung disease (RP-ILD), 33% had chronic ILD and 29% had asymptomatic ILD. Anti-Ro52 positivity was more prevalent in RP-ILD. Mortality was high in the RP-ILD group, with five deaths in eight patients. Lung transplant was life-saving intervention for three of the RP-ILD patients who survived. A review of the literature in treating RP-ILD associated with anti-MDA5 is presented. Although evidence is limited to small case series, cyclophosphamide (CYC) for refractory skin lesions, and CYC or mycophenolate mofetil plus a calcineurin inhibitor or rituximab (RTX) for RP-ILD appear efficacious. This is the largest North American case series of anti-MDA5-positive DM patients to date. There is a wide spectrum of clinical presentation of this entity. Survival is poor in those with RP-ILD; early aggressive immunosuppression and timely lung transplant were life-saving in our patients with RP-ILD.

Quality of care for cardiovascular disease prevention in rheumatoid arthritis: compliance with hyperlipidemia screening guidelines.

Objective: To evaluate compliance with hyperlipidaemia screening guidelines for cardiovascular disease prevention in RA compared with the general population. Methods: We conducted a longitudinal study of a population-based RA cohort including all prevalent cases in British Columbia between 1996 and 2006, followed up until 2010, with matched general population controls. Using administrative data, we measured compliance with general population guidelines (testing lipids every 5 years for women ⩾50 and men ⩾40), after excluding individuals with previous diabetes, coronary artery disease or hyperlipidaemia. Compliance was measured as the proportion of 5-year eligibility periods with one or more lipid test. Compliance rates in RA and controls were compared by Chi-square test. Odds ratio (95% CI) of compliance in RA (vs controls) was estimated using generalized estimating equation models, adjusting for age and sex. Mean compliance rate per patient was also calculated and compared using Mann-Whitney U test. Results: Analyses included 5587 RA individuals and 5613 controls, contributing 6993 and 7208 5-year eligibility periods, respectively. Lipids were measured in 56.6 and 59.5% of eligibility periods in RA and controls, respectively [adjusted odds ratio (95% CI): 0.97 (0.90, 1.06)]. Screening improved over time in RA relative to the general population, but remained suboptimal even after 2003, at 65.8%. Mean (s.d.) compliance rate per patient was 56.6 (47.2)% for RA and 59.5 (46.6)% for controls. Family physicians ordered almost all the lipid tests. Conclusion: Compliance with general population guidelines for hyperlipidaemia screening in RA was poor and did not differ from the general population, despite a higher risk of cardiovascular diseases.

Asthma Is Associated With Subsequent Development of Inflammatory Bowel Disease: A Population-based Case-Control Study.

BACKGROUND & AIMS: Asthma and the inflammatory bowel diseases (IBD) each arise through complex interactions between genetic and environmental factors, and share many environmental risk factors. We examined the association between asthma and Crohn's disease or ulcerative colitis. METHODS: We performed a population-based case-control study using health administrative data from the province of Alberta, Canada. The odds of a diagnosis of asthma preceding the diagnosis of either Crohn's disease (N = 3087) or ulcerative colitis (N = 2377) were compared with the odds of diagnosis of asthma among persons without IBD (N = 402,800) using logistic regression. Effect measure modification by age at diagnosis of IBD (16 years or less, 17-40 years, or older than 40 years) was tested using a likelihood ratio test. RESULTS: A diagnosis of asthma was associated with increased odds of incident Crohn's disease (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.31-1.60). No effect measure modification was observed for age at diagnosis for Crohn's disease (P = .42). However, we observed effect measure modification by age at diagnosis for ulcerative colitis (P = .0103), with an adjusted OR of 1.49 (95% CI, 1.08-2.07) among individuals diagnosed at an age of 16 years or less (OR) and an adjusted OR of 1.57 (95% CI, 1.31-1.89) among individuals diagnosed at an age older than 40 years. However, there was no association between asthma and ulcerative colitis among individuals diagnosed between ages 17 and 40 (adjusted OR, 1.05; 95% CI, 0.86-1.26). CONCLUSIONS: In a population-based case-control study, we associated asthma with Crohn's disease, and with early and late-onset ulcerative colitis.

Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general population-closing the mortality gap.

OBJECTIVE: Excess mortality in rheumatoid arthritis (RA) is expected to have improved over time, due to improved treatment. Our objective was to evaluate secular 5-year mortality trends in RA relative to general population controls in incident RA cohorts diagnosed in 1996-2000 vs 2001-2006. METHODS: We conducted a population-based cohort study, using administrative health data, of all incident RA cases in British Columbia who first met RA criteria between January 1996 and December 2006, with general population controls matched 1:1 on gender, birth and index years. Cohorts were divided into earlier (RA onset 1996-2000) and later (2001-2006) cohorts. Physician visits and vital statistics data were obtained until December 2010. Follow-up was censored at 5 years to ensure equal follow-up in both cohorts. Mortality rates, mortality rate ratios and HRs for mortality (RA vs controls) using proportional hazard models adjusting for age, were calculated. Differences in mortality in RA versus controls between earlier and later incident cohorts were tested via interaction between RA status (case/control) and cohort (earlier/later). RESULTS: 24 914 RA cases and controls experienced 2747 and 2332 deaths, respectively. Mortality risk in RA versus controls differed across incident cohorts for all-cause, cardiovascular diseases (CVD) and cancer mortality (interactions p<0.01). A significant increase in mortality in RA versus controls was observed in earlier, but not later, cohorts (all-cause mortality adjusted HR (95% CI): 1.40 (1.30 to 1.51) and 0.97 (0.89 to 1.05), respectively). CONCLUSIONS: In our population-based incident RA cohort, mortality compared with the general population improved over time. Increased mortality in the first 5 years was observed in people with RA onset before, but not after, 2000.

Mortality in ANCA-associated vasculitis: ameta-analysis of observational studies.

OBJECTIVE: To determine the magnitude of all-cause mortality risk in patients with antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) compared with the general population through a meta-analysis of observational studies. METHODS: We searched Medline and Embase databases from their inception to April 2015. Observational studies that met the following criteria were assessed by two researchers: (1) clearly defined AAV identified by either the American College of Rheumatology 1990 classification criteria or the 2012 Chapel Hill Consensus Conference disease definitions, and (2) reported standardised mortality ratios (SMR) and 95% CI. We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for all-cause mortality using random-effects model, tested for publication bias and heterogeneity. RESULTS: Ten studies met the inclusion criteria, comprising 3338 patients with AAV enrolled from 1966 to 2009, and a total of 1091 observed deaths. Overall, we found a 2.7-fold increased risk of death in patients with AAV when compared with the general population (meta-SMR: 2.71 (95% CI 2.26 to 3.24)). Analysis on studies that included only granulomatosis with polyangiitis cases also indicated a similar mortality risk (meta-SMR: 2.63 (95% CI 2.02 to 3.43)). There was no significant publication bias or small-study effect. Subgroup analyses showed that mortality risks were higher in older cohorts, with a trend towards improvement over time (ie, those with their midpoint of enrolment periods that were between 1980-1993 and 1994-1999, vs 2000-2005). CONCLUSION: Published data indicate there is a 2.7-fold increase in mortality among patients with AAV compared with the general population.

Improved survival in rheumatoid arthritis: a general population-based cohort study.

OBJECTIVE: Mortality trends of rheumatoid arthritis (RA) are largely unknown over the past decade when new drugs and management strategies have been adopted to effectively treat RA. METHODS: Using The Health Improvement Network, an electronic medical record database representative of the UK general population, we identified patients with incident RA and up to five individuals without RA matched for age, sex and year of diagnosis between 1999 and 2014. The RA cohort was divided in two sub-cohorts based on the year of RA diagnosis: the early cohort (1999-2006) and the late cohort (2007-2014). We compared mortality rates, HRs (using a Cox proportional hazard model) and rate differences (using an additive hazard model) between RA and non-RA cohorts adjusting for potential confounders. RESULTS: Patients with RA diagnosed between 1999 and 2006 had a considerably higher mortality rate than their comparison cohort (ie, 29.1 vs 18.0 deaths/1000 person-years), as compared with a moderate difference in patients with RA diagnosed between 2007 and 2014 and their comparison cohort (17.0 vs 12.9 deaths/1000 years). The corresponding absolute mortality rate differences were 9.5 deaths/1000 person-years (95% CIs 7.5 to 11.6) and 3.1 deaths/1000 person-years (95% CI 1.5 to 4.6) and the mortality HRs were 1.56 (95% CI 1.44 to 1.69) and 1.29 (95% CI 1.17 to 1.42), respectively (both p values for interaction <0.01). CONCLUSION: This general population-based cohort study indicates that the survival of patients with RA has improved over the past decade to a greater degree than in the general population. Improved management of RA and its associated comorbidities over recent years may be providing a survival benefit.

Productivity Losses and Costs in the Less-Common Systemic Autoimmune Rheumatic Diseases.

PURPOSE OF REVIEW: We synthesised the literature on productivity losses and costs in the less-common systemic autoimmune rheumatic diseases: Sjogren's syndrome (SjS), systemic sclerosis (SSc), poly/dermatomyositis (PM/DM), and systemic vasculitides (SV). RECENT FINDINGS: Of 29 studies located, 12 were published 2012 onwards (SSc = 6, SjS = 2, PM/DM = 2, SV = 2). In these, 25% of PM/DM, and 21-26% of SV, were work disabled, 22% of SSc stopped work within 3 years of diagnosis, and annual costs of absenteeism in SSc averaged $12,024 2017 USD. Very few studies reported on costs, presenteeism (working at reduced levels), or unpaid productivity loss. Across multiple systemic autoimmune rheumatic diseases (SARDs), major drivers of lost productivity were generalised items like pain, depression, and fatigue, rather than disease-specific factors. Evidence suggests that work disability is common in SSc and strikes quickly. However, in SSc and other SARDs, more comprehensive estimates are needed, which include absenteeism and presenteeism from paid and unpaid work, costs, and drivers of productivity loss.

Risk of deep venous thrombosis and pulmonary embolism in individuals with polymyositis and dermatomyositis: a general population-based study.

BACKGROUND/OBJECTIVE: Patients with polymyositis (PM) and dermatomyositis (DM) may have an increased risk of venous thromboembolism (VTE); however, no general population data are available to date. The purpose of this study was to estimate the future risk and time trends of new VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) in individuals with incident PM/DM at the general population level. METHODS: We assembled a retrospective cohort of all patients with incident PM/DM in British Columbia and a corresponding comparison cohort of up to 10 age-matched, sex-matched and entry-time-matched individuals from the general population. We calculated incidence rate ratios (IRR) for VTE, DVT and PE and stratified by disease duration. We calculated HRs adjusting for relevant confounders. RESULTS: Among 752 cases with inflammatory myopathies, 443 had PM (58% female, mean age 60 years) and 355 had DM (65% female, mean age 56 years); 46 subjects developed both diseases. The corresponding IRRs (95% CI) for VTE, DVT and PE in PM were 8.14 (4.62 to 13.99), 6.16 (2.50 to 13.92) and 9.42 (4.59 to 18.70), respectively. Overall, the highest IRRs for VTE, DVT and PE were observed in the first year after PM diagnosis (25.25, 9.19 and 38.74, respectively). Fully adjusted HRs for VTE, DVT and PE remained statistically significant (7.0 (3.34 to 14.64), 6.16 (2.07 to 18.35), 7.23 (2.86 to 18.29), respectively). Similar trends were seen in DM. CONCLUSIONS: These findings provide the first general population-based evidence that patients with PM/DM have an increased risk of VTE. Increased vigilance of this serious but preventable complication is recommended.

The risk of deep venous thrombosis and pulmonary embolism in giant cell arteritis: a general population-based study.

IMPORTANCE: Patients with giant cell arteritis (GCA) may have an increased risk of pulmonary embolism (PE), similar to other systemic vasculitidies; however, no relevant population data are available to date. OBJECTIVE: To evaluate the future risk and time trends of new venous thromboembolism (VTE) in individuals with incident GCA at the general population level. DESIGN: Observational cohort study. SETTING: General population of British Columbia. PARTICIPANTS: 909 patients with incident GCA and 9288 age-matched, sex-matched and entry-time-matched control patients without a history of VTE. MAIN OUTCOME MEASURES: We calculated incidence rate ratios (IRR) overall, and stratified by GCA duration. We calculated HR of PE and deep vein thrombosis (DVT), adjusting for potential VTE risk factors. RESULTS: Among 909 individuals with GCA (mean age 76 years, 73% women), 18 developed PE and 20 developed DVT. Incidence rates (IR) of VTE, PE and DVT were 13.3, 7.7 and 8.5 per 1000 person-years (PY) in GCA cohort, versus 3.7, 1.9 and 2.2 per 1000 PY in the comparison cohort. The corresponding IRRs (95% CI) for VTE, PE and DVT were 3.58 (2.33 to 5.34), 3.98 (2.22 to 6.81) and 3.82 (2.21 to 6.34) with the highest IRR observed in the first year of GCA diagnosis (7.03, 7.23 and 7.85, respectively). Corresponding fully adjusted HRs (95% CI) were 2.49 (1.45 to 4.30), 2.71 (1.32 to 5.56) and 2.78 (1.39 to 5.54). CONCLUSIONS AND SIGNIFICANCE: These findings provide general population-based evidence that patients with GCA have an increased risk of VTE, calling for increased vigilance in preventing this serious, but preventable complication, especially within months after GCA diagnosis.