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 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.

Background:The incidence rate (IR) and point prevalence (PP) of rheumatoid arthritis (RA) in Denmark is largely unknown. Two challenges in estimating the “true” IR and PP using nationwide registry data are the choice of the RA case definition, and the denominator used, i.e. the exact amount of person years (PY) or census count data.Objectives:To investigate the incidence and prevalence of RA in the adult Danish population using four different case definitions and two different denominator strategies.Methods:Nationwide register-based cohort study. Patients with RA between 1996 and the end of 2016 were identified using the Danish National Patient Registry (DNPR) and information on DMARD prescriptions were obtained through linkage with the Danish National Prescription Registry. Age and sex standardised incidence and prevalence of RA were calculated in different ways: we estimated the IR (denominator = actual recorded number of PY in each year using migration and vital data) and the incidence proportion (IP) (denominator = census count data); and the PP (%) of RA was calculated for years 2000, 2009, 2011 and 2016. The four case definitions were: Model A, a first time RA diagnosis (ICD-10: M05-06) in DNPR and a redeemed prescription of a conventional DMARD in the following year1; Model B, an RA diagnosis recorded twice in DNPR within 90 days with both records originating from a department of rheumatology or general internal medicine2; Model C, any RA diagnosis recorded in DNPR with a DMARD prescription redeemed in the year before or after the diagnosis; Model D, similar to Model A but with the additional requirement that cases had no registered ICD code for inflammatory diseases prior to the RA diagnosis1.Results:The overall IR of RA from 1996 to 2016 based on model A was 35.2 (95%CI 34.8 to 35.6) per 100,000 PY while the IP was 34.7 (95%CI 34.3 to 35.1) per 100,000 individuals. The age standardised IR was higher for women than for men (Figure 1), and this was observed across all age groups. The IR peaked at age 70 to 74 in both men and women. Regardless of which case definition was used, the temporal trend showed a peak in IR in 2010 followed by a plateau (Figure 2). The overall PP estimate for all four models increased from 2000 to 2016, data shown for Model A in Table 1.Table 1.Point prevalence (PP) of rheumatoid arthritis in years 2000, 2009, 2011 and 2016 based on Model A2000N = 590670.3 % women2009N = 1503770.9 % women2011N = 1736371.0 % women2016N = 2299170.3 % womenPP (%) (95% CI)PP (%) (95% CI)PP (%) (95% CI)PP (%) (95% CI)All0.16 (0.15 to 0.16)0.37 (0.36 to 0.37)0.41 (0.41 to 0.42)0.52 (0.51 to 0.52)Women0.21 (0.20 to 0.22)0.50 (0.49 to 0.51)0.57 (0.56 to 0.58)0.71 (0.70 to 0.72)Men0.10 (0.10 to 0.11)0.23 (0.22 to 0.23)0.25 (0.25 to 0.26)0.32 (0.31 to 0.33)Conclusion:A peak in the IR of RA was observed in 2010, regardless of which case definition was used. We believe this was due to introduction of the new EULAR/ACR diagnostic criteria at that time. IP estimates were systematically lower than IRs calculated using exact migration and vital data as denominator. The PP increased over time regardless of which case definition we used. We conclude that the choice of RA case definition had a larger influence than the choice of denominator.References:[1]inauskas A et al. Positive predictive value of first-time rheumatoid arthritis diagnoses and their serological subtypes in the Danish National Patient Registry. Clin Epidemiol. 2018;10:1709-1720.[2]Ibfelt E et al. Validity and completeness of rheumatoid arthritis diagnoses in the nationwide DANBIO clinical register and the Danish National Patient Registry. Clin Epidemiol. 2017:627-632.Acknowledgments:The study is funded by the Danish Rheumatism Association.Disclosure of Interests:Bolette Gylden Soussi: None declared, René Lindholm Cordtz: None declared, Salome Kristensen: None declared, Christian Sørensen Bork: None declared, Jeppe Christensen: None declared, Erik Berg Schmidt: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Lene Dreyer: None declared

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.

Objectives To investigate the 5-year all-cause mortality in patients with rheumatoid arthritis (RA) compared with the general population. Methods 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 to -1.0%) in 2011–2015, 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 2011–2015. 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 2011–2015, 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 2011–2015 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 females with RA.

Background:Few previous studies have investigated the incidence rate (IR) and point prevalence (PP) of seropositive and seronegative rheumatoid arthritis (RA), and further, the estimates remain unknown in the Danish population.Objectives:To investigate the IR and PP of seropositive and seronegative RA in the adult Danish population from 1998 to 2018 using four register-based case definitions of RA.Methods:Nationwide register-based cohort study. Using the Danish administrative registers, patients with RA between 1998 and end of 2018 were identified. ICD-10 codes for RA were identified in the Danish National Patient Registry and information on DMARD prescriptions were obtained through the Danish National Prescription Registry using ATC codes. The used case definitions were1: Criteria A, first time M05/M06 RA diagnosis and redemption of a DMARD in the following year; Criteria B, two RA diagnoses within 90 days of each other, originating from department of rheumatology or general internal medicine, where the latest registered M05/M06 diagnosis defined the serologic status; Criteria C, a M05/M06 diagnosis recorded at any time preceded or followed by redemption of a DMARD prescription within one year, where the M05/M06 diagnosis recorded determined the serologic status; Criteria D, as Criteria A, but with the additional requirements that cases had no registration for other selected inflammatory diseases.In calculation of IRs the total Danish population from 1998 to 2018 was used as reference population for standardisation. The PP was calculated for years 2000, 2009, 2011 and 2018.Results:From 1998 to 2018 the overall IR was 18.0 (95%CI 17.7 to 18.3) per 100,000 person years (PY) for seropositive RA and 16.7 (95%CI 16.4 to 16.9) per 100,000 PY for seronegative RA using Criteria A. A higher IR for seropositive RA than for seronegative RA was found regardless of the case criteria used. Figure 1 shows the temporal IRs of seropositive and seronegative RA.Regardless of case criteria used, the PP increased from 2000 to 2018 for both seropositive and seronegative RA, and the estimates were higher for seropositive RA than for seronegative RA (Table 1).Table 1.Point prevalence of rheumatoid arthritis in Denmark in year 2000, 2009, 2011 and 2018 using four different case definitions2000200920112018SeropositiveSeronegativeSeropositiveSeronegativeSeropositiveSeronegativeSeropositiveSeronegativeCriteria AN3029274174747127871281211243711662Population3964040416629842028914269677PP, % (95%CI)0.08 (0.08 to 0.08)0.07 (0.07 to 0.07)0.18 (0.18 to 0.19)0.17 (0.17 to 0.18)0.21 (0.20 to 0.21)0.19 (0.19 to 0.20)0.27 (0.27 to 0.28)0.26 (0.25 to 0.26)Criteria BN7507489311565903312710100111633413340PP, % (95%CI)0.20 (0.19 to 0.20)0.13 (0.12 to 0.13)0.28 (0.28 to 0.29)0.22 (0.21 to 0.22)0.30 (0.30 to 0.31)0.24 (0.23 to 0.24)0.36 (0.35 to 0.36)0.29 (0.29 to 0.30)Criteria CN6701457011174912512417101491588113712PP, % (95%CI)0.18 (0.17 to 0.18)0.12 (0.12 to 0.12)0.27 (0.27 to 0.28)0.22 (0.22 to 0.23)0.29 (0.29 to 0.30)0.24 (0.24 to 0.25)0.35 (0.34 to 0.35)0.30 (0.30 to 0.31)Criteria DN272423906612598476956759108309452PP, % (95%CI)0.07 (0.07 to 0.07)0.06 (0.06 to 0.07)0.16 (0.16 to 0.16)0.15 (0.14 to 0.15)0.18 (0.18 to 0.19)0.16 (0.16 to 0.17)0.24 (0.23 to 0.24)0.21 (0.20 to 0.21)PP = Point prevalenceConclusion:In Denmark, the IR and PP estimates were higher for seropositive compared to seronegative RA during the study period. However, when applying stricter case criteria for RA (Criteria A and D) the differences in IR and PP estimates were smaller, than when using less strict criteria (Criteria B and C). The findings of such small differences between seropositive and seronegative IRs warrant further investigation.References:[1]Soussi BG et al. Incidence and prevalence of rheumatoid arthritis in Denmark: a nationwide population based study investigating the effect of four different case definitions [abstract]. Ann Rheum Dis. 2020;79(supplement 1):46Acknowledgements:The authors will like to thank The Danish Rheumatism Association for supporting this work.Disclosure of Interests:Bolette Gylden Soussi: None declared, René Lindholm Cordtz: None declared, Salome Kristensen: None declared, Christian Sørensen Bork: None declared, Jeppe Christensen: None declared, Erik Berg Schmidt: None declared, Daniel Prieto-Alhambra Grant/research support from: Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA’s department and open for external participants, Lene Dreyer Grant/research support from: Grants from BMS, Galderma and Eli Lilly.