Temporal trends in mortality in patients with systemic lupus erythematosus: a Danish population-based matched cohort study.

OBJECTIVE: Excess mortality has been demonstrated in patients with SLE compared with the general population. We aimed to investigate the 5-year and 10-year all-cause mortality in patients with SLE compared with the general population in recent decades. METHODS: This was a Danish nationwide population-based exposure-matched cohort study. Incident cases of SLE diagnosed between 1996 and 2015 were identified using administrative health registries and followed until 2020, allowing for 5 and 10 years of follow-up. Patients with SLE were matched 1:5 on age and sex with individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. RESULTS: In total, 1351 incident cases of SLE and 6755 matched controls were identified. The crude risk difference (RD) for 5-year mortality decreased over the study period, from 10.3% (95% CI 6.5-14.1%) to 4.6% (95% CI 1.4-7.8%) for patients with SLE compared with controls. The relative risk (RR) for 5-year mortality decreased similarly in the same period. Adjustment for comorbidities revealed lower RD and RR for mortality in patients with SLE compared with controls, but the decreasing trend remained. The crude and adjusted RD and RR for 10-year mortality did not change over the calendar period. The 10-year RR was highest in young patients with SLE (<50 years of age). CONCLUSION: The 5-year mortality risk decreased over time for both patients with SLE and matched controls. However, excess 5-year mortality for patients with SLE in the most recent calendar period and excess mortality late in their disease course remained. Continued focus on preventing disease progression and comorbidity is required.

Temporal trends in mortality in patients with rheumatoid arthritis: a Danish population-based matched cohort study.

OBJECTIVES: To investigate the 5-year all-cause mortality in patients with RA compared with the general population. METHODS: This was a nationwide population-based matched cohort study. RA patients diagnosed between 1996 and the end of 2015 were identified using administrative heath registries and followed until the end of 2020 allowing 5 years of follow-up. Patients with incident RA were matched 1:5 on year of birth and sex with non-RA individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. RESULTS: Compared with matched controls in 1996-2000, the risk difference for RA patients ranged from 3.5% (95% CI 2.7%, 4.4%) in 1996-2000 to -1.6% (95% CI -2.3%, -1.0%) in 2011-15, and the relative risk from 1.3 (95% CI 1.2, 1.4) in 1996-2000 to 0.9 (95% CI 0.8, 0.9) in 2011-15. The age-adjusted 5-year cumulative incidence proportion of death for a 60-year-old RA patient decreased from 8.1% (95% CI 7.3%, 8.9%) when diagnosed in 1996-2000 to 2.9% (95% CI 2.3%, 3.5%) in 2011-15, and for matched controls from 4.6% (95% CI 4.2%, 4.9%) to 2.1% (95% CI 1.9%, 2.4%). Excess mortality persisted in women with RA throughout the study period, while the mortality risk for men with RA in 2011-15 was similar to their matched controls. CONCLUSIONS: Enhanced improvement in mortality was found in RA patients compared with matched controls, but for sex-specific differences excess mortality was only persistent in women with RA.

Intake of marine n-3 polyunsaturated fatty acids and the risk of rheumatoid arthritis: protocol for a cohort study using data from the Danish Diet, Cancer and Health cohort and Danish health registers.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disease with multifactorial aetiology. Smoking is a well-established lifestyle risk factor, but diet may also have an impact on the risk of RA. Intake of the major marine n-3 polyunsaturated fatty acids in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been hypothesised to lower the risk of RA due to their anti-inflammatory effects, although based on limited knowledge. Therefore, we aim to investigate the associations between dietary intake of EPA and DHA and the risk of incident RA. METHODS AND ANALYSIS: A cohort study. The follow-up design will be based on data from the Danish Diet, Cancer and Health cohort, which was established between 1993 and 1997. The participants will be followed through record linkage using nationwide registers including the Danish Civil Registration System, the Danish National Patient Registry and the Danish National Prescription Registry using the unique Civil Personal Registration number. Time-to-event analyses will be conducted with RA as the outcome of interest. The participants will be followed from inclusion until date of RA diagnosis, death, emigration or end of follow-up. HRs with 95% CIs obtained using Cox proportional hazard regression models, with age as underlying time scale and adjustment for established and potential risk factors, will be used as measures of association. ETHICS AND DISSEMINATION: The study has been approved by the Data Protection Committee of Northern Jutland, Denmark (2019-87) and the North Denmark Region Committee on Health Research Ethics (N-20190031). Study results will be disseminated through peer-reviewed journals and presentations at international conferences.

Incidence and severeness of COVID-19 hospitalization in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark.

OBJECTIVES: To estimate the incidence of COVID-19 hospitalization in patients with inflammatory rheumatic disease (IRD); in patients with RA treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalized patients with RA. METHODS: A nationwide cohort study from Denmark between 1 March and 12 August 2020. The adjusted incidence of COVID-19 hospitalization was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals. Further, the incidence of COVID-19 hospitalization was estimated for patients with RA treated and non-treated with TNF-inhibitors, HCQ or glucocorticoids, respectively. Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome or death) among hospital-admitted patients was estimated for RA and non-IRD sp - individudals. RESULTS: Patients with IRD (n = 58 052) had an increased partially adjusted incidence of hospitalization with COVID-19 compared with the 4.5 million people in the general population [hazard ratio (HR) 1.46, 95% CI: 1.15, 1.86] with strongest associations for patients with RA (n = 29 440, HR 1.72, 95% CI: 1.29, 2.30) and vasculitides (n = 4072, HR 1.82, 95% CI: 0.91, 3.64). There was no increased incidence of COVID-19 hospitalization associated with TNF-inhibitor, HCQ nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI: 0.80, 2.53) for a severe outcome. CONCLUSION: Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalization.

Reduction in Upper Limb Joint Surgery Among Rheumatoid Arthritis Patients: An Interrupted Time-Series Analysis Using Danish Health Care Registers.

OBJECTIVE: Joint replacement surgery is a proxy of severe joint damage in rheumatoid arthritis (RA). The aim of this study was to assess the impact of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the incidence rate (IR) of upper limb joint replacements among newly diagnosed RA patients. METHODS: Using the Danish National Patient Register, patients with incident RA from 1996-2012 were identified. Each patient was matched on age, sex, and municipality, with up to 10 general population controls. The age- and sex-standardized 5-year IR per 1,000 person-years of a composite outcome of any first joint replacement of the finger, wrist, elbow, or shoulder was calculated, and an interrupted time-series analysis was undertaken to investigate trends and changes of the IR in the pre-bDMARD (1996-2001) and the bDMARD eras (2003-2012), with a 1-year lag period in 2002. RESULTS: In total, 18,654 incident patients with RA were identified (mean age 57.6 years, 70.5% women). The IR of joint replacements among patients with RA was stable at 2.46 per 1,000 person-years (95% confidence interval [95% CI] 1.96, 2.96) from 1996 to 2001 but started to decrease from 2003 onwards (-0.08 per 1,000 person-years annually [95% CI -0.20, 0.02]). Compared with patients with RA, the IR among controls in 1996 was 1/17 and increased continuously throughout the study period. CONCLUSION: The IR of upper limb joint replacements started to decrease among patients with RA from 2002 onwards, whereas it increased among controls. Our results suggest an association between the introduction of bDMARDs and a lower need of joint replacements among patients with RA.