Search

Objectives To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries. Methods Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996–2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year. Results A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62–2.15)], myocardial infarction [HR 1.62 (1.26–2.09)], coronary angiogram [HR 1.64 (1.37–1.96)], percutaneous coronary intervention [HR 1.56 (1.17–2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16–3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77–2.54)], deep vein thrombosis [HR 3.13 (2.43–4.05)], pulmonary embolism [HR 4.04 (3.07–5.32)], atrial fibrillation [HR 2.08 (1.82–2.39)], ischaemic stroke [HR 1.58 (1.31–1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49–3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time. Conclusions Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time.

Objectives: In Denmark, patients with inflammatory arthritis (IA) have completed patient-reported outcome measures (PROMs) via touchscreens in the outpatient clinic since 2006. However, current technology makes it possible for patients to use their own smartphone via an application (app) developed for the Danish Rheumatology Database (DANBIO). This study aims to evaluate the agreement of PROMs between the DANBIO app and outpatient touchscreen in patients with IA. Method: Patients with IA (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis) were enrolled in a randomized, crossover, agreement study. Participants answered PROMs through the two device types in a randomized order. Differences in PROM scores with 95% confidence intervals (CIs) were evaluated for similarity according to prespecified equivalence margins. Results: The touchscreen invitation was accepted by 138 patients. Sixty patients (20 with each diagnosis) were included. The difference in Health Assessment Questionnaire Disability Index between the two device types was ���0.007 (95% CI ���0.043 to 0.030); thus, equivalence was demonstrated. In addition, all other PROMs obtained with the two device types were equivalent, except for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which was within the limits of minimally clinically important difference (MCID). In total, 78.3% preferred the DANBIO app. Conclusion: In patients with IA, equivalence was demonstrated between two device types for all PROMs except BASDAI; however, BASDAI was within the limits of the MCID. Implementation of the DANBIO app is expected to optimize outpatient visits, thereby improving healthcare for the individual patient and society.

Objective To evaluate flare risk when tapering or withdrawing biologic or targeted synthetic DMARDs (bDMARDs or tsDMARDs) compared with continuation in patients with inflammatory arthritis in sustained remission or with low disease activity. Methods Articles were identified in the Cochrane Library, PubMed, Embase and Web of Science. Eligible trials were randomized controlled trials comparing tapering and/or withdrawal of bDMARDs and/or tsDMARDs with the standard dose in inflammatory arthritis. Random effects meta-analysis was performed with risk ratio (RR) or Peto’s odds ratio (POR) for sparse events and 95% CI. Results The meta-analysis comprised 22 trials: 11 assessed tapering and 7 addressed withdrawal (4 assessed both). Only trials with an RA or axial SpA (axSpA) population were identified. An increased flare risk was demonstrated when b-/tsDMARD tapering was compared with continuation [RR 1.45 (95% CI 1.19, 1.77), I2 = 42.5%] and potentially increased for persistent flare [POR 1.56 (95% CI 0.97, 2.52), I2 = 0%]. Comparing TNF inhibitor (TNFi) withdrawal with continuation, a highly increased flare risk [RR 2.28 (95% CI 1.78, 2.93), I2 = 78%] and increased odds of persistent flare [POR 3.41 (95% CI 1.91, 6.09), I2 = 49%] were observed. No clear difference in flare risk between RA or axSpA was observed. Conclusion A high risk for flare and persistent flare was demonstrated for TNFi withdrawal, whereas an increased risk for flare but not for persistent flare was observed for b-/tsDMARD tapering. Thus tapering seems to be the more favourable approach. Registration PROSPERO (CRD42019136905).

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.

Cannabidiol (CBD) is increasingly used as analgesic medication although the recent International Association for the Study of Pain Presidential Task Force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. This trial examines CBD as add-on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized, double-blind, placebo-controlled design, patients received synthetic CBD 20 to 30 mg or placebo daily for 12 weeks. The primary outcome was pain intensity during the past 24 hours (0-100 mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale (PCS), and Health Assessment Questionnaire Disability Index. One hundred thirty-six patients were randomized, of which 129 were included in the primary analysis. Between-group difference in pain intensity at 12 weeks was 0.23 mm (95% confidence interval -9.41 to 9.90; P = 0.96). Twenty-two percent patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30 mm. We found neither clinically nor statistically significant effects of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared with placebo. In addition, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.

BACKGROUND AND AIMS Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of autoimmune systemic inflammatory diseases, with cardiovascular disease being the leading cause of death. However, large-scale real-world data on the risk of long-term cardiovascular outcomes associated with AAV are limited. Therefore, to understand, screen and optimize prevention of cardiovascular disease in AAV patients, we investigated the risk of long-term ischemic cardiovascular events, including ischemic heart disease, coronary angiogram (CAG), percutaneous coronary intervention (PCI) and ventricular arrhythmia/use of implantable cardioverter-defibrillator (ICD) devices. Secondary outcomes included heart failure (HF), atrial fibrillation (AF), stroke, venous thrombotic events and cardiac arrest. METHOD We included all incident patients with AAV diagnosed during 1996–2018. Patients were identified from the Danish nationwide healthcare registries by use of a recently validated method (positive predictive value of 97%) [1] comprising at least two consecutive hospital encounters registered as either polyangiitis with granulomatosis or microscopic polyangiitis (International Classification of Diseases, 10th Edition [ICD-10]: DM31.3 and DM31.7). Patients with AAV were matched 1:3 with controls from the general population on age and gender. We computed adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for each cardiovascular outcome, with all-cause mortality accounted for as a competing risk. G-computation of HRs was performed to estimate 5-year absolute risks standardized to the distribution of risk factors in the population. RESULTS A total of 2306 AAV patients [median age: 62.9 years (25th–75th percentile: 50.9–72.0 years), 52.6% male gender] were matched with 6918 controls. Median study follow-up was 9.5 years (25th–75th percentile: 5.3–15.8 years). Compared with controls, AAV patients had a higher rate of ischemic heart disease [HR 1.67 (95% CI 1.45–1.95)], myocardial infarction [HR 1.43 (95% CI 1.11–1.83)], CAG [HR 1.51 (95% CI 1.27–1.80)], PCI [HR 1.42 (95% CI 1.11–1.88)] and ventricular arrhythmia/ICD implantation [HR 2.03 (95% CI 1.17–3.55)]. Secondarily, AAV patients also had an increased rate of additional adverse cardiovascular events: HF [HR 1.77 (95% CI 1.48–2.11)], deep vein thrombosis [HR 2.89 (95% CI 2.24–3.72)], pulmonary embolism [HR 3.59 (95% CI 2.74–4.72)], AF [HR 1.73 (95% CI 1.51–1.98)], ischemic stroke [HR 1.34 (95% CI 1.12–1.61)] and in-hospital cardiac arrest [HR 1.97 (95% CI 1.29–2.99)]. AAV patients had a significantly increased standardized 5-year absolute risk of all outcomes except for MI, PCI and ventricular arrhythmia/ICD implantations compared with controls. CONCLUSION In this large nationwide registry-based follow-up study, AAV patients had a higher risk of ischemic cardiovascular events and were more likely to require revascularization therapy compared with matched control subjects. Moreover, AAV patients had a higher risk of HF, atrial- and ventricular arrhythmias as well as venous thrombotic events and ischemic stroke when compared with matched control subjects.

As a result of the pandemic, many patients with an inflammatory rheumatic disease (IRD) have isolated themselves. The lack of disease management together with fear of infection could lead to changes in physical- and mental health. The aim of this study was to evaluate the social- and health behaviour in patients with an IRD compared with the behaviour of healthy individuals during the COVID-19 pandemic. The study was a questionnaire survey answered by patients with an IRD and healthy individuals (HI). The questionnaire contained seven sections with questions regarding COVID-19 and quality of life including SF-36, EQ-5D-5L, and visual analogue scale (VAS) pain, fatigue and global health. Of 1663 invited participants, 661 patients with IRD and 266 HI were included in the analyses. Patients with an IRD felt more isolated during the COVID-19 pandemic compared with HI (IRD: 9.5% (61/644), HI: 3.1% (8/259), p-value = 0.001). More HI (5.4%) had been infected with COVID-19 than patients with an IRD (1.7%). Among patients with an IRD those with worse self-reported disease activity outcomes (VAS pain, fatigue and global health, all p-value

Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce. Funding Agencies|NORDFORSK [90825]; Swedish Research Council [2018-02803]; Swedish innovation Agency (Vinnova); Innovationsfonden; The Research Council of Norway; Region Stockholm-Karolinska Institutet; Region Vasterbotten (ALF); Danish Rheumatism Association [R194-A6956, A1923, A3037, A3570]; Swedish Brain Foundation; Nils and Bibbi Jensens Foundation; Knut and Alice Wallenberg Foundation; Margaretha af Ugglas Foundation; South-Eastern Heath Region of Norway; Health Research Fund of Central Denmark Region; Region of Southern Denmark; A.P. Moller Foundation for the Advancement of Medical Science; Colitis-Crohn Foreningen; Novo Nordisk Foundation [NNF15OC0016932]; Aase og Ejnar Danielsens Fond; Beckett-Fonden; Augustinus Fonden; Knud and Edith Eriksens Mindefond; Laege Sofus Carl Emil Friis and Hustru Olga Doris Friis Legat; Psoriasis Forskningsfonden; University of Aarhus; Region of Southern Denmarks PhD Fund [12/7725]; Department of Rheumatology, Frederiksberg Hospital; Research Council of Norway [229624, 223273]; South East and Western Norway Health Authorities; ERC AdG project SELECTionPREDISPOSED; Stiftelsen Kristian Gerhard Jebsen; Trond Mohn Foundation; Novo Nordisk Foundation; University of Bergen

Objectives: The objectives of this study were to investigate the incidence of COVID-19 hospitalization in unvaccinated and vaccinated patients with RA compared with matched controls, and in patients with RA according to DMARD treatment.Methods: This was a Danish nationwide matched-cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalization (Danish National Patient Register) and first-time positive SARS-CoV-2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PYs) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals.Results: In total, 28 447 unvaccinated patients and 568 940 comparators had IRs for COVID-19 hospitalization of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PYs, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding IRs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PYs (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV-2 and 1.09 (0.92-1.14) among vaccinated RA patients. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalization compared with conventional DMARD-treated patients.Conclusion: The incidence of COVID-19 hospitalization was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients. Objectives: The objectives of this study were to investigate the incidence of COVID-19 hospitalization in unvaccinated and vaccinated patients with RA compared with matched controls, and in patients with RA according to DMARD treatment.Methods: This was a Danish nationwide matched-cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalization (Danish National Patient Register) and first-time positive SARS-CoV-2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PYs) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals.Results: In total, 28 447 unvaccinated patients and 568 940 comparators had IRs for COVID-19 hospitalization of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PYs, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding IRs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PYs (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV-2 and 1.09 (0.92-1.14) among vaccinated RA patients. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalization compared with conventional DMARD-treated patients.Conclusion: The incidence of COVID-19 hospitalization was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.

OBJECTIVE: Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis.METHODS: We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.FINDINGS: The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab.INTERPRETATION: Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history.FUNDING: None.

Objectives It has been hypothesized that the presence of chronic pain causes excess mortality. Since chronic pain is prevalent among patients with PsA this potential association should be explored. We aimed to investigate whether higher cumulative pain intensity is associated with an excess mortality risk in patients with PsA. Methods A nested case–control study using data from the nationwide DANBIO Register (Danish Database for Biological Therapies in Rheumatology) Register and Danish healthcare registers. Cases were patients who died and corresponding to the date of death, matched on sex, year of birth and calendar period at the time of death with up to five controls. Exposure of interest was mean pain intensity reported during the time followed in routine rheumatology practice. Pain intensity was measured using a visual analogue scale from 0 to 100 and conditional logistic regression was used to calculate odds of mortality per 5 unit increase in pain while adjusting for confounders. Results The cohort consisted of 8019 patients. A total of 276 cases were identified and matched with 1187 controls. Higher mean pain intensity was associated with increased odds of mortality [odds ratio 1.06 (95% CI 1.02, 1.10)] in the crude model, but there was no association [odds ratio 0.99 (95% CI 0.95, 1.03)] when adjusting for additional confounders. Factors shown to increase the odds of mortality were recent glucocorticoid use, concomitant chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease. Conclusion These results indicate that experienced pain in itself is not associated with premature mortality in patients with PsA. However, recent glucocorticoid use and concurrent comorbidities were.

Objectives Patient-reported outcome measures (PROMs) are evaluated in randomized controlled trials (RCTs) in patients with systemic lupus erythematosus (SLE), but not widely used in clinical practice. However, interest in incorporating PROMs into the management of SLE is increasing as PROMs provide a unique insight into the patient’s perception of lupus disease activity. The objective was to assess agreement in PROMs answered using a web app versus an outpatient touchscreen among patients with SLE. Methods In a crossover RCT, SLE patients answered the following PROMs in a random order using the web app and the outpatient touchscreen: Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) Global Health, SLAQ Symptom, SLAQ Total, SLAQ Worsening, Pain Visual Analog Scale (VAS), Fatigue VAS, Patient Global Health VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Acceptable Symptom State (PASS), and an Anchoring Question. Equivalence between the two device types was demonstrated if the 95% confidence interval (95% CI) of the difference in PROM scores was within the prespecified equivalence margin. Agreement between the two device types was assessed using mixed linear models. Results Thirty-four patients with SLE were included. Equivalence was demonstrated between the two device types for SLAQ Global Health with a difference of −0.21 (95% CI: −0.65 to 0.23). Moreover, equivalence was also found for HAQ-DI, Pain VAS, and Fatigue VAS whereas only comparability within the limits of the Minimal Clinically Important Difference (MCID) was demonstrated for VAS Patient Global Health. Statistical comparability was demonstrated for SLAQ Total, SLAQ Worsening, PASS, and Anchoring Question (no predefined MCID/equivalence margins available). However, a statistically significant difference between device types was observed for the SLAQ Symptom of −0.56 (95% CI: −1.10 to −0.01). The difference was, however, very small when considering the scale range of 0–24; thus, it was not judged to be of clinical relevance. Preference for the web app was very high (91.2%). Conclusion For the first time ever, equivalence and comparability between two electronic device types for various PROMs were demonstrated among patients with SLE. Implementation of the device is expected to improve the management of SLE.

Background: Patients with systemic lupus erythematosus (SLE) have an increased risk of infections due to impaired immune functions, disease activity, and treatment. This study investigated the impact of having SLE on the incidence of hospitalisation with COVID-19 infection. Methods: This was a nationwide cohort study from Denmark between 1 March 2020 to 2 February 2021, based on the linkage of several nationwide registers. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with SLE compared with the general population in Cox-regression models. Among SLE patients, the hazard ratio (HR) for hospitalisation was analysed as nested case-control study. Results: Sixteen of the 2533 SLE patients were hospitalised with COVID-19 infection. The age-sex adjusted rate per 1000 person years was 6.16 (95% CI 3.76–10.08) in SLE patients, and the corresponding hazard ratio was 2.54 (95% CI 1.55–4.16) compared with the matched general population group after adjustment for comorbidities. Among SLE patients, hydroxychloroquine treatment was associated with a HR for hospitalisation of 0.61 (95% CI 0.19–1.88), and 1.06 (95% CI 0.3–3.72) for glucocorticoid treatment. Conclusion: Patients with SLE were at increased risk of hospitalisation with COVID-19.

The pathogenesis of psoriatic arthritis (PsA) involves inflammation and bone and soft tissue turnover. Dietary fatty acids have previously been associated with pro-inflammatory effects induced by saturated fatty acids (SFA) and anti-inflammatory effects achieved by at least some polyunsaturated fatty acids (PUFA). The aim of the study was to investigate the correlations between the content of fatty acids in granulocytes and clinical and biochemical markers of PsA. A total of 140 patients with PsA were included. Skin and joint disease activity were assessed. Fatty acid composition in granulocytes was determined by gas chromatography. Competitive enzyme-linked immunosorbent assays were used to assess bone and soft tissue turnover. The content of SFA, n-6 PUFA or n-3 PUFA in granulocytes was not associated with disease activity. Marine n-3 PUFA was significantly positively correlated with collagen degradation. In contrast, n-6 PUFA was significantly positively correlated with collagen formation and negatively correlated with collagen degradation. However, the correlations were all weak. No association was found between the content of fatty acids in granulocytes and disease activity in this population of patients with PsA. The correlation between fatty acids and biomarkers of bone and soft tissue turnover needs further investigation.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013–Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1

Background: To estimate the incidence of COVID-19 hospitalisation in patients with vasculitis, and to evaluate the impact of glucocorticoid treatment on the outcome between March 2020 and February 2021. Methods: With use of the Danish nationwide registers, a cohort of patients with large (LVV) and small vessel vasculitis (SVV), respectively, and general population controls (GPCs) matched on age and gender was established. Hazard ratios (HR) for COVID-19 hospitalisation was estimated. National COVID-19 surveillance data was used to calculate the odds ratio (OR) of having had a positive SARS-CoV2 PCR test. Lastly, a nested case-control design and conditional logistic regression was used to estimate the impact of glucocorticoids on the risk of hospitalisation. Findings: Patients with SVV (n=1090) had an increased incidence of COVID-19 hospitalisation compared with GPCs (comorbidity-adjusted HR 2·73; 95% CI 1·64-4·55), whereas no increased risk was seen in patients with LVV. Patients with vasculitis had similar likelihoods of having had a positive PCR test as GPCs. Glucocorticoids did not increase the HR of hospitalisation among patients with LVV or SVV. Interpretation: Patients with SVV were more likely to be admitted with COVID-19 than the GPCs. The impact of glucocorticoid treatment on the risk of hospitalisation needs further investigation. Funding Information: The study was sponsored by Aalborg University Hospital, Denmark. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Declaration of Interests: RLC, JL and SK have no disclosures or conflicts of interests. CTP has received grants for studies from Bayer and Novo Nordisk not relevant to the current study. LD has received research grant/research support from BMS, and speakers bureau from EliLilly and Galderma. Ethics Approval Statement: According to Danish legislation, no ethics approval is needed for register-based studies. The study has been approved by the Data Protection Committee of Northern Jutland, Denmark (2020-032).

Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients. Prolargin—an extracellular matrix (ECM) protein present in cartilage and tendon—has been previously shown elevated in serum of patients with psoriasis. ECM protein fragments can reflect tissue turnover and pathological changes; thus, this study aimed to develop, validate and characterize a novel biomarker PROM targeting a matrix metalloproteinase (MMP)-cleaved prolargin neo-epitope, and to evaluate it as a biomarker for PsA. A competitive ELISA was developed with a monoclonal mouse antibody; dilution- and spiking-recovery, inter- and intra-variation, and accuracy were evaluated. Serum levels were evaluated in 55 healthy individuals and 111 patients diagnosed with PsA by the CASPAR criteria. Results indicated that the PROM assay was specific for the neo-epitope. Inter- and intra- assay variations were 11% and 4%, respectively. PROM was elevated (p = 0.0003) in patients with PsA (median: 0.24, IQR: 0.19–0.31) compared to healthy controls (0.18; 0.14–0.23) at baseline. AUROC for separation of healthy controls from PsA patients was 0.674 (95% CI 0.597–0.744, P

Recent international guidelines recommend the use of biosimilar biological drugs on similar terms as their corresponding originators, including switching from a bio-originator to the biosimilar.1 However, the comparative safety of biosimilars in patients with inflammatory joint diseases (IJD) in routine care is still debated.2 In a phase 3 randomised trial among patients with rheumatoid arthritis, biosimilar etanercept (SB4) had slightly more hepatobiliary adverse events compared with the originator (ETN), possibly explained by differences in patients’ comorbid diseases and comedication use.3 The occurrence of, for example, hepatobiliary safety events is likely to differ across indications (due to differences in age, body weight, use of methotrexate, comedication, etc) and has not been explored in etanercept-treated patients with psoriatic arthritis or axial spondyloarthritis.4 In April 2016, a mandatory switch from ETN to SB4 was performed in Denmark to save costs and the 1-year clinical …

Thank you for the interest1 in our recent publication, in which we explored treatment outcomes following a Danish mandatory switch from originator to biosimilar etanercept (SB4, 50 mg) in routine care.2 We showed that of the 2061 patients who were receiving originator etanercept and thus were eligible for the switch, as many as four of five (79%) switched to the biosimilar, despite the continued availability of the originator drug (as 25 mg pen or 50 mg powder solution). Among the patients who switched, we observed high retention rates of the biosimilar. The 6-month …

ObjectivesAccording to guidelines, a nationwide non-medical switch from originator (INX, Remicade) to biosimilar infliximab (Remsima, CT-P13) was conducted in Danish patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). We investigated disease activity before/after switching and retention rates in the DANBIO registry.MethodsDisease activities 3 months before and after switch and changes over time were calculated. Flare was defined as change in 28 Joint Disease Activity Score (∆DAS28) ≥1.2 (RA/PsA) or Ankylosing Spondylitis Disease Activity Score (∆ASDAS) ≥1.3 (AxSpA). Crude and adjusted retention rates were compared with a historic cohort of INX-treated patients.ResultsEight hundred and two patients switched (403 RA/120 PsA/279 AxSpA; 51% women, age (median (IQR): 55 (44-66)) years). Follow-up was 413 (339–442) days. Prior INX treatment duration was 6.8 (4.3–9.5) years. Disease activities were similar 3 months before/after switch. Crude 1-year CT-P13 retention rate (84.1 (95% CI 81.3 to 86.5)) was similar to the historic IFX cohort (86.2 (95% CI 84.0 to 88.0), p=0.22). The adjusted absolute retention rates were 83.4 (95% CI 80.8 to 86.2) and 86.8% (95% CI 84.8 to 88.8), respectively (p=0.03). In total 132 patients withdrew (lack of effect: 71/132=54%, adverse events: 37/132=28%). Patients with previous INX treatment duration >5 years had longer CT-P13 retention.ConclusionIn 802 arthritis patients treated with INX for median >6 years, a nationwide non-medical switch to CT-P13 had no negative impact on disease activity. Adjusted 1-year CT-P13 retention rate was slightly lower than for INX in a historic cohort.

Background:Patient-reported outcome measures (PROMs) are essential to understand the patient’s perception of arthritis activity. In Demark, PROMs are registered on a touchscreen in the outpatient clinic. However, some patients find it inconvenient due to e.g. waiting in queue, lack of privacy, uncomfortable seating position, reduced upper limb strength and dexterity with seeing the touchscreen due to deformity of the cervical spine. The widespread use of smartphones makes it possible for patients to register PROMs via an application (app) on their own device.Objectives:The primary aim is to evaluate the agreement (i.e. similarity) between the two devices assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI) status among patients with inflammatory arthritis.Methods:The study was a randomised, crossover, agreement trial (NCT03486613) conducted at Aalborg University Hospital, Denmark. Participants were recruited through an invitation on the touchscreen in the outpatient clinic. Patients with an established diagnosis (≥ 12 months) of rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) and experience with the PROM questionnaires (≥ 3 previous registrations) were enrolled and randomised in ratio 1:1 (stratified by diagnosis) to PROM registration through the DANBIO app and the touchscreen in random order. Figure 1A and 1B shows the two devices.The sample size calculation was based on a prespecified equivalence margin of ±0.11 HAQ-DI points (i.e. ≤ half of the minimal important difference of 0.22 points) yielding a power of 99.2% for 60 enrolled patients. There was a wash-out period of 1-2 days between the two device registrations to minimise the potential carryover effect.A paired t-test was used to calculate the mean HAQ-DI score for the two devices and the difference in HAQ-DI score with a 95% confidence interval (CI). A Bland-Altman plot was used to assess limits of agreement (LoA).Results:60 patients (20 with RA, 20 with PsA and 20 with axSpA) were randomised of whom 51.7% were male. Mean age was 53.7 years (range 22-77) and mean disease duration was 12.5 years (range 1.0-34.8).Mean HAQ-DI was 0.608 (95%CI 0.437;0.779) for the DANBIO app and 0.614 (95%CI 0.446;0.783) for the touchscreen (Table 1). Agreement between scores obtained with the two devices is illustrated with Bland-Altman plots in figure 2A and 2B. The paired mean difference of HAQ-DI between the two devices was -0.006 (95%CI -0.0424; 0.030); thus the 95% confidence interval for the mean difference was within the prespecified equivalence margin of ±0.11 HAQ-DI points.Table 1.HAQ-DI scores, difference and LoA for the two devices.App, mean (SD)Touchscreen, mean (SD)Difference, mean (95%CI)LoAMissing valuesHAQ-DI (0-3)0.608 (0.656)0.614 (0.646)-0.006 (-0.042;0.030)-0.277;0.2641Conclusion:The current study showed no statistical or clinically important difference in HAQ-DI measurement captured by a smartphone app or outpatient touchscreen. Therefore, we feel confident that the two devices perform similarly enough to be used interchangeably in patients with inflammatory arthritis.Disclosure of Interests:Line Uhrenholt Speakers bureau: Abbvie, Eli Lilly and Novartis (not related to the submitted work), Robin Christensen: None declared, Lene Dreyer: None declared, Annette Mortensen Speakers bureau: MSD and Eli Lilly (not related to the submitted work)., Ellen-Margrethe Hauge Speakers bureau: Fees for speaking/consulting: MSD, AbbVie, UCB and Sobi; research funding to Aarhus University Hospital: Roche and Novartis (not related to the submitted work)., Niels Steen Krogh: None declared, Mikkel Kramme Abildtoft: None declared, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Salome Kristensen: None declared

BACKGROUND/OBJECTIVE: Autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been associated with an impaired function of the autonomic nervous system and reduced vagus nerve (VN) tone measured through lower heart rate variability (HRV). Targeting the VN through electrical stimulation has been proposed as a treatment strategy with promising results in patients with RA. Moreover, it has been suggested that the VN can be stimulated physiologically through deep breathing. In this study, the aim was to investigate if the VN can be stimulated through deep breathing in patients with RA and SLE, as measured by HRV.METHODS: Fifty-seven patients with RA and SLE performed deep breathing exercises for 30 minutes in this explorative study. Before the breathing exercise, 2 electrocardiogram recordings were obtained to determine the patient's baseline HRV during rest. After the 30-minute breathing exercise, 5 minutes of electrocardiogram recordings were obtained to determine postintervention HRV and used as a measure of vagal activity.RESULTS: No change was observed in the HRV between the 2 recordings prior the exercise, but the heart rate and HRV significantly decreased and increased, respectively, after the deep breathing exercise.CONCLUSIONS: HRV can be modulated in patients with RA and SLE; this may have implications for future treatment with medications in conjunction with deep breathing. However, the biological and clinical effect of deep breathing must be investigated in future studies.

Background With our increasing understanding of cross-talk between the immune system (immune cells, cytokines) and extracellular matrix (ECM) of the affected tissues, ECM destruction and turnover has gained a lot of attention in inflammatory arthritis. ECM mainly consists of interstitial matrix (rich in type I and III collagens) and basement membrane (mainly composed of type IV collagen), both of which are affected in inflammatory arthritis. We hypothesize that inflammatory milieu in Psoriatic Arthritis (PsA) leads to accelerated ECM destruction and remodeling, and the release of ECM metabolites into circulation, that can be measured in serum as biomarkers of tissue remodeling and may give insight to pathological process at the tissue level. Objectives This prospective study aimed to use serological biomarkers for evaluation of the extent of damage to, and changes in turnover of ECM in patients with PsA and to investigate their relation to inflammatory biomarkers and disease activity. Methods Patients with PsA (n=145) fulfilling the CASPAR criteria and above 18 years of age with any disease activity were recruited through outpatient department in Aalborg University Hospital, Denmark. Exclusion criteria were pregnancy, treatment with biological DMARD, or with oral corticosteroids and other comorbidities. Clinical disease parameters were recorded, and blood samples were collected at baseline and 24 weeks follow-up. Inflammation-related ECM remodelling was measured by serological biomarkers of type I, III and IV collagen formation (Pro-C1, Pro-C3 and Pro-C4, respectively) and MMP-mediated degradation (C1M, C3M and C4M respectively). The chronic inflammation was measured by CRPM (MMP degraded metabolite of CRP). All biomarkers were measured by competitive ELISAs and levels were compared to the reference levels of healthy individuals. The biomarker data was log2 transformed for normalization and standard parametric statistical methods were applied. Results We found that there was an increase in the degradation of interstitial matrix (represented by C1M and C3M) which was uncompensated with either decreased (Pro-C1) or unaltered (Pro-C3) formation in patients with PsA as compared to healthy individuals. On the contrary, there was a compensated increase in basement membrane remodeling in patients with PsA as represented by increase in both C4M and Pro-C4 in comparison to healthy individuals (Table 1). Interestingly, there was a strong correlation between baseline C4M and Pro-C4 (r=0.703, p Conclusion Chronic inflammation underlying PsA pathology results in an increased amount of ECM turnover that correlates with clinical progression and can be measured by serological biomarkers. References None Disclosure of Interests Samra Sardar Employee of: I am a full time employee at Nordic Bioscience, Salome Kristensen: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Jeppe Christensen: None declared, Morten Karsdal Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Annette Mortensen: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience

Objectives In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA). Methods Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months’ remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication). Results Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months’ remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched. Conclusion This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.

Background:Studies regarding excess mortality among patients with psoriatic arthritis (PsA) are conflicting due to the heterogenous nature of the disease. Thus, identifying risk factors for mortality is crucial, but few studies have examined these in PsA. Presence of chronic pain can cause excess mortality and since pain is prevalent among patients with PsA this association should be explored.Objectives:To investigate whether higher cumulative pain intensity is associated with an excess mortality ratio in patients with PsA.Methods:A nested case-control study was performed using data from the national Danish healthcare registers and the DANBIO rheumatology register. Cases were patients who died while followed in routine care. Cases were matched on sex, year of birth and calendar period of DANBIO entry with up to five controls. The main exposure of interest was the mean pain intensity (all causes) reported during the time followed in routine rheumatology practice. The pain intensity was measured on a visual analogue scale (VAS) ranging from 0 (no pain) to 100 (worst imaginable pain). Conditional logistic regression was used to calculate the odds of mortality per 5 unit increase in VAS pain while adjusting for inflammatory markers.Results:The Danbio PsA cohort consisted of 8019 patients. In total, 266 cases, i.e. PsA patients who died during the observational period, were identified and matched with 1198 controls (4.5 controls per case). Increasing pain intensity was associated with increased odds of mortality (OR 1.05, 95%CI 1.01 to 1.09) in the crude model, but the association disappeared when adjusting for age, sex, calendar time, socioeconomic status, average c-reactive protein and swollen joint count during the observation period (OR 0.98, 95%CI 0.93-1.03).Age, average CRP, biological DMARD use, glucocorticoid use, and comorbidities (see table) increased the odds of mortality.Tableregression estimates from fully adjusted modelOdds Ratio95% CIAge2,731,60-4,68C-reactive protein1,051,03-1,07Swollen joint count1,080,97-1,22Health assessment questionnaire1,250,84-1,86bDMARD use2,621,51-4,57cDMARD use0,690,46-1,03Glucocorticoid use3,902,51-6,05Chronic obstructive pulmonary disease2,191,20-4,02Diabetes mellitus2,651,62-4,31Cancer6,153,88-9,76Cardiovascular disease2,611,71-3,97Conclusion:These results indicate that experienced pain in itself is not associated with excess mortality. Age, recent glucocorticoid use, biological DMARD use, chronic pulmonary disease, diabetes, cancer and cardiovascular disease were all associated with an increased mortality.Disclosure of Interests: :None declared

Background:Patients with systemic lupus erythematosus (SLE) experience significant fatigue, a debilitating symptom associated with reduced quality of life. A simple, reliable multidimensional method for assessing fatigue has not yet been validated for Danish patients with SLE.Objectives:The primary objective was to study the internal consistency, test-retest reliability, and construct validity (convergent and discriminant validity) of the multidimensional Modified Fatigue Impact Scale (MFIS) in patients with SLE. The secondary objective was to investigate the contribution of disease activity and organ damage to fatigue.Methods:Data from the ”Bio and Genome Bank Study in Centre for SLE and Vasculitis” obtained through routine visits were used. Fatigue was assessed using the MFIS and Short Form 36 (SF36). Internal consistency of the MFIS was assessed with Cronbach’s alpha (α). Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). Construct validity was studied using Spearman’s rank correlation coefficient (rs) and Principal Component Analysis (PCA) between MFIS and SF36 vitality (VT-SF36) and mental health (MH-SF36) subscales. Association between MFIS and disease activity and organ damage was estimated with Spearman’s rank correlation coefficient.Results:The study included 30 patients with SLE. Internal consistency of the MFIS was excellent with Cronbach’s α = 0.97 for the complete scale. Excellent test-retest reliability was found with ICC = 0.95 (95% confidence interval: 0.88-0.98, p < 0.05). Construct validity was confirmed by Spearman’s correlation (VT-SF36: rs= −0.73, p < 0.001 (Fig. 1). MH-SF36: rs= −0.74, p < 0.001 (Fig. 2)) and PCA with explained variance from the first two principal components (PC) (VT-SF36: PC1 = 60.2%, PC2 = 8.5%. MH-SF36: PC1 = 58.5%, PC2 = 7.4%). No significant correlation was found between the MFIS and SLEDAI (rs= 0.04, p = 0.84) or SLICC Damage Index (rs= 0.32, p = 0.08).Figure 1.Scatter plot of the Modified Fatigue Impact Scale (MFIS) and the Short Form 36 vitality (VT-SF36) subscale.Figure 2.Scatter plot of the Modified Fatigue Impact Scale (MFIS) and the Short Form 36 mental health (MH-SF36) subscale.Conclusion:The present study found the multidimensional assessment of fatigue with MFIS to be a reliable and valid instrument in SLE. The MFIS might provide more detailed information about fatigue in future studies. In agreement with some previous studies we found no association between fatigue and SLEDAI or SLICC which raises questions about the cause of this symptom. Further and larger studies are needed to investigate if any association between fatigue and disease components exist.Disclosure of Interests:None declared

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

ObjectivesReal-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised.MethodsObservational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted).Results1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months’ preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers’ clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective.ConclusionSeventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

Mesenteric vasculitis is the most common abdominal manifestation of vasculitis and can present as acute abdominal pain. Mesenteric vasculitis is most frequent in systemic lupus erythematosus and polyarteritis nodosa in adulthood and immunoglobulin A-vasculitis in childhood. Involvement of other organs is also seen. The diagnosis can be challenging, but detailed clinical assessment in combination with diagnostic tests often identifies the underlying cause. Medical treatment is used, when the abdominal manifestation is considered reversible, while surgery is used in unstable patients or patients with non-reversible conditions.

Background In Denmark, patients (pts) treated with originator etanercept (ETA) 50 mg SC conducted a mandatory non-medical switch to biosimilar SB4 in April 2016 (switchers). Pts treated with 25 mg ETA or 50 mg powder-solution were not mandated to switch (non-switchers). Some switchers resumed ETA during follow-up (back-switchers). Objectives To investigate the frequency of back-switching after the non-medical switch from ETA to SB4, and in back-switchers to study, 1) baseline characteristics at the time of initial switch (ETA->SB4), 2) reasons for SB4 withdrawal, 3) changes in disease activity during treatment with SB4 and after back-switching. Methods Patient data were retrieved from the DANBIO registry (censored August 2017). For back-switchers, disease activity at the start of SB4 (=baseline) and at the time of back-switching to ETA were compared, and changes in disease activity between the two time points were calculated (=delta values), stratified by indication (RA/PsA/AxSpA). Baseline characteristics of back-switchers were compared to the rest of the switch population (Chi-sq, Mann-Whitney U-test). Abbreviations are shown in table 1. Results 1641 pts switched from ETA to SB4. Of these, 299 (18%) withdrew SB4 therapy during 1 year follow-up and either switched back to ETA (n=120, 7%), started another bDMARD (n=104), died (n=9), were lost to follow-up (n=1) or did not re-start bDMARDs (n=65). Among the 120 back-switchers, SB4 was withdrawn due to LOE (52%), AE (39%), or other/unknown reasons (9%). The reasons for withdrawal of SB4 in back-switchers are listed in table 1. No major safety events occurred. The median time on SB4 before back-switching was 120 (IQR 73–193) days, and the time between stop of SB4 and re-start of ETA was 11–1 days. Baseline characteristics of back-switchers vs the rest of the switch population were similar (all p>0.05). Among back-switchers who stopped SB4 due to LOE, PGA increased during SB4 treatment, whereas CRP and SJC were largely unchanged (table 1). At the date of censoring, 104/120 back-switchers (87%) were still treated with originator ETA (median treatment duration 236 (155–302) days). Conclusions In a nationwide cohort of 1621 arthritis patients that were switched from ETA to SB4, 7% switched back to ETA. Back-switchers had no distinct clinical or disease characteristics upon start of SB4. AEs prior to back-switching were largely unspecific. In pts who withdrew SB4 due to LOE, PGA had increased. Reasons for back-switching appeared to be predominantly subjective rather than objective (nocebo effect). Originator drug was still available (25 mg or 50 mg powder-solution), which may have encouraged back-switching. References [1] Glintborg, et al. Arthritis Rheum2017;69(suppl 10). [2] Glintborg, et al. Abstract, EULAR2018. Acknowledgements Partly sponsored by Biogen Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, Pfizer, I. Sorensen: None declared, E. Omerovic: None declared, F. Mehnert: None declared, N. Manilo: None declared, K. Danebod: None declared, D. Jensen: None declared, H. Nordin: None declared, A. G. Loft Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, O. Hendricks Grant/research support from: Abbvie, Roche, Novartis, S. Chrysidis: None declared, B. Andersen: None declared, J. Raun: None declared, H. Lindegaard: None declared, J. Espesen: None declared, S. Jakobsen: None declared, I. M. Hansen Grant/research support from: Roche, E. Dalsgaard: None declared, D. Pedersen: None declared, S. Kristensen: None declared, A. Linauskas: None declared, L. Andersen: None declared, J. Grydehoj: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB

Background In Denmark, rheumatoid arthritis(RA), psoriatic arthritis(PsA) and axial spondyloarthritis(AxSpA) patients (pts) treated with originator etanercept (ETA) 50 mg SC conducted a mandatory non-medical switch to biosimilar Etanercept (SB4) in April 2016 (switchers). Pts treated with 25 mg ETA or 50 mg powder solution were not mandated to switch (non-switchers). Objectives To characterise switchers and non-switchers, and to compare 1 year treatment retention in switchers with non-switchers and a historic cohort of ETA treated pts. Methods Pt data were retrieved from the DANBIO registry and national registries. We applied Chi-square/Mann-Whitney for comparisons and Kaplan-Meier/Cox regression analyses (crude, adjusted for gender/age/MTX/remission/comorbidities/ETA-start-year) for drug retention. The historic cohort encompassed pts treated with ETA by Jan 1st 2015. Results Of 2,061 ETA treated pts by April 2016, 79% switched to SB4 (933RA/351PsA/337AxSpA), whereas 21% (286RA/56PsA/98AxSpA) continued ETA. In RA, compared to switchers, non-switchers more often received 25 mg ETA, had higher disease activity and HAQ (table 1). Similar patterns were seen for PsA and AxSpA. Median(IQR) follow-up was 383(314–414)days. In all 3 cohorts, withdrawals were mainly due to lack of effect. Retention rate was lowest in non-switchers (figure 1). 1 year adjusted rates were 83% (95% CI 79–87) in switchers, 77%(72–82 in non-switchers and 90%(88–92 in historic cohort. Pts not in remission had poorer retention than pts in remission both in switchers (hazard ratio 1.7 (1.3–2.2) and non-switchers (2.4 (1.7–3.6)). Numbers are medians (IQR) unless otherwise stated. * DAS28 Conclusions Of >2000 ETA treated pts, ≈80% switched to SB4. Non-switchers had higher disease activity and more often received 25 mg ETA. Switchers had poorer retention rate than a historic ETA-cohort, but better than non-switchers. Withdrawal was most common in pts not in remission. These real-world data indicate that a switching-to-biosimilar option facilitated clinical decision making in standard care, leading to withdrawal from ineffective therapy in both switchers and non-switchers. Acknowledgements Partly sponsered by Biogen Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, Pfizer, I. Sorensen: None declared, E. Omerovic: None declared, F. Mehnert: None declared, N. Manilo: None declared, K. Danebod: None declared, D. Jensen: None declared, H. Nordin: None declared, A. G. Loft Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, O. Hendricks Grant/research support from:: Abbvie, Roche, Novartis, S. Chrysidis: None declared, B. Andersen: None declared, J. Raun: None declared, H. Lindegaard: None declared, J. Espesen: None declared, S. Jakobsen: None declared, I. M. Hansen Grant/research support from: Roche, E. Dalsgaard: None declared, D. Pedersen: None declared, S. Kristensen: None declared, A. Linauskas: None declared, L. Andersen: None declared, J. Grydehoj: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB

Background In Denmark, biological drugs are provided free by the hospitals to the patients via a tax-based system. In 2015 a non-medical switch from originator infliximab to CT-P13 was conducted (1). According to national guidelines in April 2016, a non-medical switch from originator (ETA, Enbrel® 50 mg/week) to biosimilar etanercept (SB4, Benepali®) was dictated when SB4 was marketed, including patients with inflammatory rheumatic diseases treated in routine care. Objectives To investigate 3 months9 disease activity and 5 months9 treatment withdrawal in ETA-treated patients (pts) with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthrits (SpA), who were switched to SB4 and monitored prospectively in the DANBIO registry. Methods Pts with RA/PsA/SpA followed in DANBIO since start of first bDMARD were included. Disease activity at 3 months before switch (pre-switch), at the switch and after 3 months (post-switch) and changes over time (Δpre-switch and Δpost-switch) were calculated. Disease flare was defined as ΔDAS28≥1.2 (RA/PsA) or ΔASDAS≥1.3 (SpA). Factors associated with withdrawal (gender/age/diagnosis/bDMARD-treatment-no/comedication methotrexate/baseline CRP/patient9s global score) were explored by multivariable Cox regression analysis. Results In total, 1548 switch pts were identified (891 RA, 335 PsA, 322 SpA). 60% were women, age (median (IQR) 56 (44–65) yrs)). Prior ETA treatment duration was 5.2 (3.2–8.0) yrs. ETA was the first biological treatment in 49%, and the second in 33% of pts. Concomitant MTX was given in 60% (RA)/49% (PsA)/15% (SpA). Median follow-up time was 154 (110–178) days. Disease activity remained largely unchanged 3 months prior to vs. after the switch (Table). The proportion of patients with disease flare pre-/post switch was 8%/13% (RA), 9%/13% (PsA), 5%/5% (SpA). Overall, 129 pts (9%) stopped SB4 treatment during 5 months9 follow-up (Table). Prior ETA treatment duration in these patients was 4.5 (2.7–7.1) years. Higher patient9s global score (HR 1.12/cm, 95% CI (1.05–1.21), p=0.002) and no concomitant methotrexate (HR 2.28 (1.48–3.52), p Conclusions In 1548 patients with inflammatory rheumatic diseases treated with ETA for >5 years, disease activity was largely unaffected in the majority of patients 3 months after non-medical switch to SB4 and comparable to the fluctuations observed in the 3 months prior to the switch. Several patients (≈9%) stopped treatment during 5 months follow-up. Higher patient9s global score and no use of methotrexate were associated with withdrawal. Longer follow-up will offer additional understanding of the potential efficacy and safety consequences of the non-medical switch. References Glintborg et al. Arthritis Rheumatol. 2016; 68 (suppl 10): Abstract no 951. Acknowledgements Data analysis was partly financially supported by Biogen. Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, I. Sorensen: None declared, A. G. Loft: None declared, J. Esbesen: None declared, H. Lindegaard: None declared, D. Jensen: None declared, K. Danebod: None declared, S. Dieperink: None declared, O. Hendricks: None declared, I. M. Hansen Grant/research support from: Roche, A. Linauskas: None declared, S. Kristensen: None declared, L. Andersen: None declared, M. Hossein: None declared, H. Nordin: None declared, B. Andersen: None declared, S. Chrysidis: None declared, J. Raun: None declared, N. Manilo: None declared, J. Grydehoj: None declared, E. Dalgaard: None declared, D. Pedersen: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Orion, BMS, AbbVie, Biogen, Pfizer, MSD, Eli Lilly

Background: Patients with psoriatic arthritis are at high cardiovascular risk. Marine n-3 polyunsaturated fatty acids (PUFA) may reduce the incidence of cardiovascular disease. The aim of this study was to investigate the effect of marine n-3 PUFA on cardiac autonomic function and vascular function in patients with psoriatic arthritis. Methods: The study was conducted as a randomized, double-blind, placebo-controlled trial, where 145 patients with psoriatic arthritis were supplemented with 3 g of n-3 PUFA or olive oil (control) daily for 24 weeks. Blood pressure, heart rate, HRV, central blood pressure, pulse wave velocity (PWV) and fatty acid composition of granulocytes, were determined. Results: At baseline we found a significant difference in the HRV parameter RR when comparing subjects with the highest vs the lowest fish intake (p = 0.03). After supplementation for 24 weeks there was a trend towards an increase in RR (p= 0.13) and decrease in heart rate (p = 0.12) comparing the n-3 PUFA group with the control group. However, per-protocol analysis (performed on participants who completed the trial with a good compliance) showed significantly increased RR (p = 0.01) and lowered heart rate (p = 0.01) in the n-3 PUFA supplemented patients compared to controls. Blood pressure, PWV and central blood pressure did not change after supplementation with n-3 PUFA. Conclusions: Marine n-3 PUFA increased HRV in patients with psoriatic arthritis which may suggest a protective effect of n-3 PUFA against cardiovascular disease in this population.

Thank you for the interest in our publication based on data from the Danish DANBIO registry regarding 2061 patients who were eligible for a mandatory non-medical switch from originator to biosimilar etanercept in routine care.1 2 The marketing of biosimilars has changed the landscape of the biological drugs with the potential for huge cost reductions, most markedly if patients may be switched from an ongoing successful treatment with the expensive originator to a much cheaper biosimilar. Thus, up to 75% price reduction has been experienced in Denmark so far with no evidence of increased use of health resources.3 The outcomes of a non-medical switch of etanercept in the real-world setting are, however, largely unknown, since prevous publications on switching in routine care have included limited numbers of patients. The aim of the study was therefore to investigate the effectiveness of a large-scale, …