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Objective This study aimed to compare the prevalence and incidence of polyautoimmunity between anticyclic citrullinated peptide antibody (anti-CCP)–positive and anti-CCP–negative patients with rheumatoid arthritis (RA). Methods In a nationwide register-based cohort study, patients with RA (disease duration ≤ 2 yrs) in the DANBIO rheumatology register with an available anti-CCP test in the Register of Laboratory Results for Research were identified. The polyautoimmunity outcome included 21 nonrheumatic autoimmune diseases identified by linkage between the Danish Patient Registry and Prescription Registry. The age- and sex-adjusted prevalence ratio (PR) was calculated by modified Poisson regression to estimate the prevalence at diagnosis in anti-CCP–positive vs anti-CCP–negative patients. The hazard ratio (HR) of polyautoimmunity within 5 years of entry into DANBIO was estimated in cause-specific Cox regression models. Results The study included 5839 anti-CCP–positive and 3799 anti-CCP–negative patients with RA. At first visit, the prevalence of prespecified polyautoimmune diseases in the Danish registers was 11.1% and 11.9% in anti-CCP–positive and anti-CCP–negative patients, respectively (PR 0.93, 95% CI 0.84-1.05). The most frequent autoimmune diseases were autoimmune thyroid disease, inflammatory bowel disease, and type 1 diabetes mellitus. During a mean follow-up of 3.5 years, only a few (n = 210) patients developed polyautoimmunity (HR 0.6, 95% CI 0.46-0.79). Conclusion Polyautoimmunity as captured through the Danish National Patient Registry occurred in approximately 1 in 10 patients with RA at time of diagnosis regardless of anti-CCP status. In the years subsequent to the RA diagnosis, only a few and mainly anti-CCP–negative patients developed autoimmune disease., Objective. This study aimed to compare the prevalence and incidence of polyautoimmunity between anticyclic citrullinated peptide antibody (anti-CCP)–positive and anti-CCP–negative patients with rheumatoid arthritis (RA). Methods. In a nationwide register-based cohort study, patients with RA (disease duration ≤ 2 yrs) in the DANBIO rheumatology register with an available anti-CCP test in the Register of Laboratory Results for Research were identified. The polyautoimmunity outcome included 21 nonrheumatic autoimmune diseases identified by linkage between the Danish Patient Registry and Prescription Registry. The age- and sex-adjusted prevalence ratio (PR) was calculated by modified Poisson regression to estimate the prevalence at diagnosis in anti-CCP–positive vs anti-CCP–negative patients. The hazard ratio (HR) of polyautoimmunity within 5 years of entry into DANBIO was estimated in cause-specific Cox regression models. Results. The study included 5839 anti-CCP–positive and 3799 anti-CCP–negative patients with RA. At first visit, the prevalence of prespecified polyautoimmune diseases in the Danish registers was 11.1% and 11.9% in anti-CCP–positive and anti-CCP–negative patients, respectively (PR 0.93, 95% CI 0.84-1.05). The most frequent autoimmune diseases were autoimmune thyroid disease, inflammatory bowel disease, and type 1 diabetes mellitus. During a mean follow-up of 3.5 years, only a few (n = 210) patients developed polyautoimmunity (HR 0.6, 95% CI 0.46-0.79). Conclusion. Polyautoimmunity as captured through the Danish National Patient Registry occurred in approximately 1 in 10 patients with RA at time of diagnosis regardless of anti-CCP status. In the years subsequent to the RA diagnosis, only a few and mainly anti-CCP–negative patients developed autoimmune disease.

Objective To examine whether patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV. Methods Using a nested case–control framework, patients with granulomatosis with polyangiitis and microscopic polyangiitis were identified through the Danish Nationwide Registries from 1996 to 2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), ischaemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischaemic stroke, pericarditis and ventricular arrhythmias/implantable cardioverter defibrillator implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date. Results A total of 2371 patients with AAV (median age 63 years, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared with 3.8% [HR 3.05 (95% CI 2.48–3.75)] and 1.3% [HR 1.98 (95% CI 1.39–2.82)] of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: any cardiovascular outcome [HR 10.73 (95% CI 7.05–16.32)] and MACE [HR 5.78 (95% CI 2.67–12.52)]. In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA). Conclusions AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance towards cardiovascular disease., OBJECTIVE: To examine if patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV.METHODS: Using a nested case-control framework, patients with Granulomatosis with polyangiitis and Microscopic polyangiitis were identified through Danish Nationwide Registries from 1996-2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV-diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted Hazard Ratios (HRs) for major adverse cardiovascular events (MACE), ischemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, and ventricular arrhythmias/ICD-implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date.RESULTS: A total of 2371 patients with AAV (median age: 63yrs, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared to 3.8% (HR 3.05[2.48-3.75]) and 1.3% (HR 1.98[1.39-2.82]) of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: Any cardiovascular outcome (HR 10.73[7.05-16.32]) and MACE (HR 5.78[2.67-12.52]). In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA).CONCLUSIONS: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance toward cardiovascular disease.

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 tempora

OBJECTIVES: To investigate the incidence of COVID-19 hospitalisation in unvaccinated and vaccinated patients with rheumatoid arthritis (RA) compared with matched controls, and in patients with RA according to DMARD treatment.METHODS: 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 hospitalisation (Danish National Patient Register) and first-time positive SARS-CoV2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PY) 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 hospitalisation of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PY, 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 PY (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-CoV2 and 1.09 (0.92-1.14) among vaccinated. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalisation compared with conventional DMARD treated patients.CONCLUSION: The incidence of COVID-19 hospitalisation 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.

Background Polyautoimmunity is defined as having 2 or more autoimmune diseases. Little is known about polyautoimmunity in patients with cutaneous lupus erythematosus (CLE). Objectives To estimate prevalence and 5-year incidence of non–lupus erythematosus (LE) autoimmune diseases in patients with CLE. Methods Patients with CLE were identified In the Danish National Patient Registry and each patient was age- and sex-matched with 10 general population controls. Outcome information on non-LE autoimmune diseases was obtained by register-linkage between Danish National Patient Registry and the National Prescription Register. The risk ratio (RR) for prevalent non-LE autoimmune disease at time of CLE diagnosis was calculated in modified Poisson regression; and hazard ratios (HRs) for incident non-LE autoimmune disease were estimated in Cox regression analyses. Results Overall, 1674 patients with CLE had a higher prevalence of a non-LE autoimmune disease than the comparators (18.5 vs 7.9%; RR 2.4; 95% CI, 2.1 to 2.6). Correspondingly, the cumulative incidence of a non-LE autoimmune disease during 5 years of follow-up was increased for the patients with CLE: HR 3.5 (95% CI, 3.0 to 4.0). Limitations Risk of detection and misclassification bias, mainly pertaining to the CLE group. Conclusion Patients with CLE had higher prevalence and 5-year cumulative incidence of a non-LE autoimmune disease than the general population., Background: Polyautoimmunity is defined as having 2 or more autoimmune diseases. Little is known about polyautoimmunity in patients with cutaneous lupus erythematosus (CLE). Objectives: To estimate prevalence and 5-year incidence of non–lupus erythematosus (LE) autoimmune diseases in patients with CLE. Methods: Patients with CLE were identified In the Danish National Patient Registry and each patient was age- and sex-matched with 10 general population controls. Outcome information on non-LE autoimmune diseases was obtained by register-linkage between Danish National Patient Registry and the National Prescription Register. The risk ratio (RR) for prevalent non-LE autoimmune disease at time of CLE diagnosis was calculated in modified Poisson regression; and hazard ratios (HRs) for incident non-LE autoimmune disease were estimated in Cox regression analyses. Results: Overall, 1674 patients with CLE had a higher prevalence of a non-LE autoimmune disease than the comparators (18.5 vs 7.9%; RR 2.4; 95% CI, 2.1 to 2.6). Correspondingly, the cumulative incidence of a non-LE autoimmune disease during 5 years of follow-up was increased for the patients with CLE: HR 3.5 (95% CI, 3.0 to 4.0). Limitations: Risk of detection and misclassification bias, mainly pertaining to the CLE group. Conclusion: Patients with CLE had higher prevalence and 5-year cumulative incidence of a non-LE autoimmune disease than the general population.

Objectives: Kidney involvement and medical compliance are frequent challenges in systemic lupus erythematosus (SLE). Additional data reporting such as absolute risk estimates may strengthen risk stratification and compliance. This study provides absolute risk estimations of risk of new-onset proteinuria among SLE patients. Methods: Danish SLE centres provided clinical data on first time observations of proteinuria and other clinical parameters listed in the 1997 American College of Rheumatology Classification Criteria for SLE. Time from first occurring non-renal manifestation to new-onset proteinuria or censoring defined time at risk. Multivariate Cox-regression models were used to identify risk factors for new-onset proteinuria and to calculate risk of proteinuria stratified by risk factor debut age, duration, and sex. Results: The patient population consisted of 586 patients with SLE, mainly Caucasian (94%) women (88%), mean age at inclusion of 34.6 years (standard deviation, SD=14.4 years), observed for a mean of 14.9 years (SD=11.2 years). The cumulative prevalence of proteinuria was 40%. Discoid rash, HR =0.42 (p=0.01) and lymphopenia HR=1.77 (p=0.005) were associated with new-onset proteinuria. Male patients with lymphopenia had the highest predictive risks of proteinuria with a 1-, 5- and 10-year risk of proteinuria ranging from 9-27%, 34-75% and 51-89%, depending on the age at presentation (debut at 20, 30, 40 or 50 years). The corresponding risk profiles for women with lymphopenia were 3-9%, 8-34% and 12-58%, respectively. Conclusions: Large differences in absolute risk estimates for new-onset proteinuria were identified. The differences may aid risk stratification and patient compliance among high-risk individuals., OBJECTIVES: Kidney involvement and medical compliance are frequent challenges in systemic lupus erythematosus (SLE). Additional data reporting such as absolute risk estimates may strengthen risk stratification and compliance. This study provides absolute risk estimations of risk of new-onset proteinuria among SLE patients. METHODS: Danish SLE centres provided clinical data on first time observations of proteinuria and other clinical parameters listed in the 1997 American College of Rheumatology Classification Criteria for SLE. Time from first occurring non-renal manifestation to new-onset proteinuria or censoring defined time at risk. Multivariate Cox-regression models were used to identify risk factors for new-onset proteinuria and to calculate risk of proteinuria stratified by risk factor debut age, duration, and sex. RESULTS: The patient population consisted of 586 patients with SLE, mainly Caucasian (94%) women (88%), mean age at inclusion of 34.6 years (standard deviation, SD=14.4 years), observed for a mean of 14.9 years (SD=11.2 years). The cumulative prevalence of proteinuria was 40%. Discoid rash, HR =0.42 (p=0.01) and lymphopenia HR=1.77 (p=0.005) were associated with new-onset proteinuria. Male patients with lymphopenia had the highest predictive risks of proteinuria with a 1-, 5- and 10-year risk of proteinuria ranging from 9–27%, 34–75% and 51–89%, depending on the age at presentation (debut at 20, 30, 40 or 50 years). The corresponding risk profiles for women with lymphopenia were 3–9%, 8–34% and 12–58%, respectively. CONCLUSIONS: Large differences in absolute risk estimates for new-onset proteinuria were identified. The differences may aid risk stratification and patient compliance among high-risk individuals.

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

Objective Successful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). Methods Observational cohort study from the DANBIO registry. Patients were classified as originator-naïve or originator-experienced. Retention rates of 1-year GP1111 treatment were explored (Kaplan-Meier). We identified baseline factors (at the time of switch) associated with withdrawal of GP1111 (multivariable Cox-regression analyses with HRs including originator treatment history). Changes in subjective and objective measures of disease activity 4 months before and after the switch were assessed in individual patients. Results Of 1605 patients (685 RA, 314 PsA and 606 AxSpA, median disease duration was 9 years, 37% in Clinical Disease Activity Index/Ankylosing Spondylitis Disease Activity Score remission), 1171 were originator-naïve. Retention rates at 1-year were 83% (95% CI: 81% to 85%) and 92% (95% CI: 90% to 95%) for the originator-naïve and originator-experienced, respectively. GP1111 retention rates were higher in originator-experienced compared to originator-naïve with RA (HR=0.4 (95% CI: 0.2 to 0.7)) and PsA (HR=0.2 (95% CI: 0.1 to 0.8)), but not significantly for AxSpA: HR=0.6 (95% CI: 0.3 to 1.2). Lower disease activity was associated with higher retention. Changes in disease activity preswitch and postswitch were close to zero. Conclusion This real-world observational study of more than 1600 patients with inflammatory arthritis showed high 1-year retention following a nationwide infliximab biosimilar-to-biosimilar switch. Retention was higher in originator-experienced and in patients with low disease activity, suggesting outcomes to be affected by patient-related rather than drug-related factors.

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, ther

Objectives SLE displays large clinical heterogeneity that beyond genetic factors may be determined by environmental exposures. In this Danish nationwide study, we aimed to determine if clinical subsets of SLE were associated with smoking history. Methods At each of six participating centres, incident or prevalent inpatients and outpatients with SLE were consecutively included. Manifestations forming the basis of SLE classification were registered in an electronic chart system. Patients also provided questionnaire-based data on environmental exposures, including smoking history. Hierarchical cluster analysis was conducted to determine and characterise subsets of patients with similar traits of disease manifestations. Levels of smoking exposure by pack-years were correlated to the identified SLE subsets, as well as discrete SLE manifestations. Results The cohort consisted of 485 patients (88% women and 92% Caucasian) with SLE of which 51% were ever smokers. Common disease manifestations comprised non-erosive arthritis (81%), malar rash (57%), lymphopenia (55%), photosensitivity (50%) and persistent proteinuria (41%). We identified three distinct phenotypic clusters characterised by their preponderance of (A) neurological, serosal and mucosal involvement; (B) renal, haematological and immunological disorders; and (C) acute and chronic skin manifestations. Cluster B was the youngest and had the lowest level of smoking exposure. Age-adjusted regression analyses showed that compared with never smokers a smoking history of >20 pack-years was associated with neurological disorder (OR=3.16), discoid rash (OR=2.22), photosensitivity (OR=2.19) and inversely with haematological disorder (OR=0.40), renal disorder (OR=0.40) and non-erosive arthritis (OR=0.45), p<0.05 for all. Conclusions Our findings support that SLE presents in varying clinical phenotypes and suggest that they may have differentiated associations with smoking history.

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

(1) Polymyalgia rheumatica (PMR) is an inflammatory disease characterised by pain, morning stiffness, and reduced quality of life. Recently, vagus nerve stimulation (VNS) was shown to have anti-inflammatory effects. We aimed to examine the effect of transcutaneous VNS (t-VNS) on PMR. (2) Fifteen treatment-naïve PMR patients completed the study. Patients underwent a 5-day protocol, receiving 2 min of t-VNS stimulation bilaterally on the neck, three times daily. Cardiac vagal tone (CVT) measured on a linear vagal scale (LVS), blood pressure, heart rate, patient-reported outcome, and biochemical changes were assessed. (3) t-VNS induced a 22% increase in CVT at 20 min after initial stimulations compared with baseline (3.4 ± 2.2 LVS vs. 4.1 ± 2.9 LVS, p = 0.02) and was accompanied by a 4 BPM reduction in heart rate (73 ± 11 BPM vs. 69 ± 9, p < 0.01). No long-term effects were observed. Furthermore, t-VNS induced a 14% reduction in the VAS score for the hips at day 5 compared with the baseline (5.1 ± 2.8 vs. 4.4 ± 2.8, p = 0.04). No changes in CRP or proinflammatory analytes were observed. (4) t-VNS modulates the autonomic nervous system in patients with PMR, but further investigation of t-VNS in PMR patients is warranted.

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.

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.

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 < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (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.

Objectives Real-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. Methods Observational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted). Results 1621 (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. Conclusion Seventy-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.