DANBIO Registry Research Articles

Counting the costs: a nationwide study on healthcare use following an adalimumab biosimilar switch in >1300 inflammatory arthritis patients.

In Denmark, cost savings motivate mandatory biosimilar switches. In 2018, patients switched from originator to biosimilar adalimumab, that is, to GP2017 in Eastern and to SB5 in Western Denmark. However, concerns were raised about additional costs covering, that is, an increased number of outpatient visits due to patient education, treatment monitoring, and patient concerns. To investigate whether the switch led to increased total healthcare costs, defined as costs related to in- and outpatient contacts in hospitals and the primary sector and use of prescription medicine (excluding biological treatment). Observational cohort study with geographical cluster pseudo-randomization. Patients with rheumatoid arthritis, psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA), who switched were identified in the nationwide DANBIO registry. Total healthcare costs 9 months before and after the switch were captured from the National Patient and Prescription registries. The difference between pre- and post-switch costs was estimated by a generalized estimation equations (GEE) model. Overall, 1316 patients switched to GP2017 (n = 621) or SB5 (n = 695). Total healthcare costs were mainly driven by hospital costs. The monthly fluctuations of hospital costs 9 months before and after the switch were largely similar or decreased. In the adjusted analyses (GEE), hospital costs decreased after the switch (by approximately 15%) for GP2017 switchers, especially PsA (estimate = 0.83; 95% CI 0.75-0.92) and AxSpA patients (estimate = 0.85; 0.77-0.93), with no significant changes for SB5 switchers. We found no increase in total healthcare costs in 9 months following a nationwide mandatory adalimumab originator to biosimilar switch. Our findings were strengthened by similar results for GP2017 and SB5.

JAK-inhibitors and risk on serious viral infection, venous thromboembolism and cardiac events in patients with rheumatoid arthritis: A protocol for a prevalent new-user cohort study using the Danish nationwide DANBIO register.

Janus Kinase inhibitors (JAKis) are targeted synthetic disease-modifying antirheumatic drugs and represent an important alternative to treat patients with moderate to high rheumatoid arthritis (RA) disease activity. Safety concerns associated with increased risk for venous thromboembolism (VTE), serious viral infection, and, more recently, major adverse cardiovascular events (MACE) in JAKi users have emerged worldwide. However, as the exact mechanisms to explain these safety concerns remain unclear, the increased risk of VTE, MACE, and serious viral infection in JAKi users is heavily debated. In light of the need to enrich the safety profile of JAKis in real-world data, we aim to quantify the incidence and risk of MACE, VTE, and serious viral infections in RA patients registered in the Danish DANBIO registry, a nationwide registry of biological therapies used in rheumatology. Therefore, we will conduct a population-based cohort study using a prevalent new-user design. We will identify all RA patients in the DANBIO, ≥ 18 years old, receiving a JAKi or a tumor necrosis factor α inhibitor (TNF-αi) from January 2017 to December 2022. Prevalent and new users of JAKis will be matched to TNF-αi comparators with similar exposure history using time-conditional propensity scores (TCPS). We will describe the cumulative incidence of the outcomes (VTE, MACE, serious viral infection) in each exposure group (JAKi users; TNF-αi users), stratified by outcome type. Additionally, the Aalen-Johansen method will be used to estimate the time-to-event survival function stratified by outcome type. We will also estimate the hazard ratio (HR) with 95% confidence interval (CI) of each outcome in both exposure groups using the time-dependent Cox proportional hazards model. Results will enrich the safety profile of JAKis in real-world data.

Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: a nationwide nested case–control study

ObjectivesTo assess how biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids and disease activity affect risk of Staphylococcus aureus bacteraemia (SAB) in patients with rheumatoid arthritis (RA).MethodsIn a nationwide cohort of patients...

Infliximab biosimilar-to-biosimilar switching in patients with inflammatory rheumatic disease: clinical outcomes in real-world patients from the DANBIO registry

ObjectiveSuccessful 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),...

Conversion of the MDHAQ to the HAQ score: a simple algorithm developed and validated in a cohort of 13 391 real-world patients.

To develop and validate in real-world patients a conversion algorithm from the Multidimensionel Health Assessment Questionnaire physical function scale (MDHAQ) to the Stanford Health Assessment Questionnaire disability index physical function scale (HAQ) score. From the DANBIO registry, 13 391 patients with RA (n = 8983), PsA (n = 2649) and axial spondyloarthritis (axSpA, n = 1759) with longitudinal data on HAQ and MDHAQ were included, stratified by diagnosis, and randomized 1:1 into development and validation cohorts. Conversion algorithms were developed by linear regression and applied in validation cohorts. From MDHAQ, the HAQ was calculated (cHAQ) and validated against the observed HAQ for criterion, correlational and construct validity. For RA, we developed the conversion algorithm cHAQ = 0.15+MDHAQ*1.08, and validated it in the RA validation cohort. Criterion validity: HAQ and cHAQ had comparable discriminative power to distinguish between high and low patient global scores (standardized mean difference: HAQ:-1.29, cHAQ:-1.35). Kappa value between HAQ and cHAQ functional states indicated good agreement (0.83). Correlational validity: baseline HAQ and cHAQ, respectively, correlated well with patient global scores (r = 0.65/0.67). Bland-Altman plots showed good agreement across all functional states. Construct validity: HAQ and cHAQ discriminated equally well between patients reporting symptom state as acceptable vs not, and across responses to an external anchor. Aiming for a common algorithm, the RA conversion algorithm was validated for PsA and axSpA with similar results. This study suggests that in observational datasets with only the MDHAQ available, a simple algorithm allows valid conversion to HAQ on the group level in RA, PsA and axSpA.

Enthesitis in patients with psoriatic arthritis and axial spondyloarthritis – data from the Danish nationwide DANBIO registry

ObjectiveTo explore the registration, pattern and burden of clinical enthesitis among routine-care patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in the Danish nationwide DANBIO registry. MethodsIn patients with PsA and axSpA in DANBIO, prospectively registered data from 2010 to 2020 on clinical entheseal assessment using SPARCC score were compared with demographic, clinical and patient-reported-outcome (PRO) data. Results6582 PsA and 5547 axSpA patients had their first registration in DANBIO in 2010 or later (“incident cohort”). At these registrations, 1037 (16%) PsA and 1188 (21%) axSpA patients had entheseal assessments, with ≥1 enthesitis being found in 66% and 39%, respectively. Mean enthesitis scores were 2.5 (PsA) and 1.3 (axSpA). Most common sites were: Achilles tendon (right/left/symmetrical: PsA:24.4%/23.3%/17.1%; axSpA:10.4%/10.6%/8.0%), lateral epicondyle (PsA:22.2%/20.1%/16.2%; axSpA:.4%/9.7%/7.6%), plantar fascia (PsA:17.1%/17.0%/12.6%; axSpA:10.4%/10.6%/8.0%), greater trochanter (PsA:14.2%/15.4%/11.7%; axSpA:9.9%/11.2%/8.2%). Enthesitis was more frequent in women (PsA/axSpA 61%/62%) than men (39%/37%). Patients with vs without enthesitis had higher overall burden (higher physician global, swollen/tender joint counts, pain, fatigue, patient global; fewer in patient-acceptable-symptom-state (PASS)) (all p < 0.05). Comparable demographic, clinical and PRO-results in patients with missing entheseal assessments, support the data being representative. In an “overall” cohort of all patients with ≥1 entheseal assessments after 2010, results on enthesitis were comparable. ConclusionEntheseal assessments were only performed at a minority of clinical visits. Clinical enthesitis was frequent, particularly in women, often symmetrical and associated with a higher physician- and patient-reported disease burden in patients with PsA and axSpA treated in routine practice, emphasizing the need for systematic assessment in routine care.

Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases-An Interim Report from a Danish Prospective Cohort Study.

Background/Purpose: In light of the current COVID-19 pandemic, whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease-modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV-2 vaccinations remains a major concern. There is an urgent need for more SARS-CoV-2 vaccine efficacy data to inform healthcare providers on the potential need for a booster vaccine. We established the ‘Detection of SARS-CoV-2 antibodies in Danish Inflammatory Rheumatic Outpatients’ study (DECODIR) in March 2021 in order to assess and compare the immunoglobulin G (IgG response) of the SARS-CoV-2 BNT162b2 vaccine (Pfizer, Groton, CT, USA/BioNTech, Mainz, Germany) and mRNA-1273 vaccine (Moderna, Cambridge, MA, USA) administered as part of the national vaccine roll out in patients with RMDs, irrespective of treatment. Patients’ SARS-CoV-2 IgG level was used as proxy to determine vaccination response. Methods: The study is a longitudinal prospective cohort study in which the SARS-CoV-2 antibody response was measured and compared at baseline and at six weeks following vaccination. The study population consisted of patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA), or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg. Bloods, patient reported outcome measurements (PROMS), clinical data, and treatment information (cs/bDMARD) were collected at baseline/6 weeks and documented in the Danish DANBIO registry. Commercially available antibody tests (ThermoFisher, Waltham, MA, USA) were used, and SARS-CoV-2 IgG levels were reported in EliA U/mL. Sufficient IgG response was defined as ≥10 EliA U/mL (manufacturers cut-off). Associations between antibody response, age, gender, disease (RA/PsA/SpA), no treatment or cs/bDMARD treatment, and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR), and bootstrapped 95% confidence interval (CI) of the median. Results: A total of 243 patients were included. We observed a significant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 34.5 EliA U/mL at 6 weeks). Seventy-two patients (32%) had an insufficient IgG response. The median IgG level in patients treated with cs/bDMARD combination therapy was significantly lower compared to patients without any DMARD treatment (12 EliA U/mL vs. 92 EilA U/mL (p < 0.01)). Conclusion: Patients treated with a combination of cs/bDMARD are at significantly higher risk of an inadequate response to SARS-CoV-2 vaccines as measured by IgG level compared to patients without DMARD treatment. IgG SARS-CoV-2 are only part of the immune response, and further data are urgently needed. At present, our results may inform healthcare providers and policy makers on the decision for the need of a booster vaccine in this particular patient group.

Characteristics of participants and decliners from a randomized controlled trial on physical activity in patients with rheumatoid arthritis: a retrospective register-based cross-sectional study

Objective A randomized controlled trial [Joint Resources – Sedentary Behaviour (JR-SB) intervention] aimed to reduce sedentary behaviour and increase light-intensity physical activity in patients with rheumatoid arthritis (RA) through motivational counselling and text messages. Since a large proportion of invited patients declined to participate, this study aims to compare sociodemographic, clinical, and lifestyle factors between included patients and patients declining to participate (non-participants) in the JR-SB study and to investigate which characteristics were associated with participation. Method A register-based cross-sectional study was conducted. All patients invited to participate in the JR-SB study were identified in the DANBIO registry, from which patients’ clinical and lifestyle data were also retrieved. Data on sociodemography and comorbidity were extracted from national registers. Differences between participants and non-participants were determined by an independent t-test or a chi-squared test. Logistic regression analyses adjusted for various confounders tested the association of patient characteristics with the likelihood of participation in the JR-SB study. Results A total of 467 (58%) declined participation in the JR-SB study. Non-participants were older and less educated, more were smokers, fewer performed regular physical activity, and more had comorbidity compared to participants. Regression analyses showed that a higher educational level and absence of comorbidity in particular were associated with participation in the JR-SB study. Conclusion Patients with RA who are less educated and with certain types of comorbidity are less motivated to participate in a physical activity intervention. The findings may inform the recruitment process and implementation of physical activity interventions in rheumatology clinical practice.

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.

We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549 rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele ORMeta=0.83, P Meta=0.000077; P Het=0.61). In addition, we found that each copy of the LRRC55 rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; P Het=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; P Het=0.45; P Interaction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the MAFB rs6071980 and CNTN5 rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; P Het=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; P Het=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; P Het=0.12; P Interaction=0.032). Mechanistically, we found that subjects carrying the LINC02549 rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549 rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55 rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated.

Impact of the COVID-19 pandemic on treat-to-target strategies and physical consultations in >7000 patients with inflammatory arthritis.

ObjectivesTo explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease, as well as to explore characteristics of patients with/without physical consultations in the clinic and the impact of early vs established disease.MethodsPatients with RA, PsA or axial SpA (axSpA) prospectively followed in the nationwide DANBIO registry answered online questionnaires and reported patient-reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO [all patients and subgroups with early disease (disease duration ≤2 years)]. In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age, gender, education level, comorbidities, disease duration, treatment).ResultsWe included 7836 patients (22% of eligible patients), 12% of which had early disease. PROs were stable before and during the pandemic, with median changes approximating zero, as well as in patients with early disease. Remission rates were stable. The relative decrease in the number of patients with physical consultations was 21–72%, which was highest in axSpA. Characteristics of patients with/without physical consultations were similar. Self-reported satisfaction with treatment options and access was >70%; the preferred contact form was physical consultation (66%).ConclusionIn this nationwide study performed during the first 8 months of the pandemic, patient satisfaction was high and the PROs and remission rates remained stable despite the remarkable reduction in physical consultations, as well as in patients with early disease. Characteristics of patients with/without physical consultations appeared similar.

POS1170 SELF-PROTECTION STRATEGIES, HEALTH BEHAVIOR AND DISEASE ACTIVITY DURING THE FIRST WAVE, RE-OPENING AND SECOND WAVE OF THE COVID-19 PANDEMIC IN &gt;7000 DANISH PATIENTS WITH INFLAMMATORY ARTHRITIS

Background:The COVID-19 pandemic has caused lockdown, reduced access to face-to-face consultations, anxiety about taking immunosuppressive agents and self-isolation1 which potentially impact rheumatic disease control negatively. However, changes in behavior including self-protection strategies during the ongoing pandemic and impact on rheumatic disease activity have only been scarcely described.The first COVID-19 wave hit Denmark in March 2020 followed by a gradual re-opening from mid-April and the second surge began in the late autumn of 2020.Objectives:To describe changes over time in self-protection strategies and health behavior during the first 8 months of the COVID-19 pandemic and to explore impact on self-reported disease activity and quality of life (=patient reported outcomes, PROs) in patients with inflammatory rheumatic disease (IRD) in DANBIO.Methods:Patients were invited to answer two on-line questionnaires regarding current behavior and disease specific PROs: One in June 2020 (including also questions regarding behavior in March 2020), and one in November 2020. Responses were linked to PROs collected as part of routine care before March 2020 (=Before) in DANBIO. For each PRO, changes (=delta values) between the two timepoints were calculated in individual patients.Results:Overall, 7,836 patients (22% of eligible patients) answered both questionnaires and were included (rheumatoid arthritis(RA): 5270(67%), psoriatic arthritis(PsA): 1217(15%), axial spondyloarthritis(AxSpA): 932(12%), other IRD: 417(5%). Patients reported highest levels of anxiety and self-protection in March with an improvement in June that was largely unchanged in November (Figure 1), e.g. proportions staying at home avoiding others as much as possible (completely or mostly agree) were 87%/49%/51% in March/June/November, respectively (Figure 1, Panel C).Disease activity and proportions of patients reporting acceptable symptom state remained stable at the three time points (Table 1), with all median delta values being close to zero (not shown).Conclusion:In this large cohort of patients with inflammatory rheumatic diseases followed in the nationwide DANBIO registry, COVID-19 related self-protection strategies were highest in March 2020, but more than half of the patients also reported self-isolation in June and November. We found no negative impact of the pandemic on patient-reported outcomes, which remained largely unchanged and were similar to before the pandemic. The latter finding probably reflects that few patients reduced or withdrew from treatment due to fear of COVID-19.1

POS0056 ANXIETY AND CONCERNS RELATED TO THE WORK SITUATION DURING THE COVID-19 PANDEMIC IN &gt;5,000 PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASE FOLLOWED IN THE DANISH DANBIO REGISTRY, RESULTS FROM A NATIONWIDE QUESTIONNAIRE

Background:During the COVID-19 pandemic, widespread changes in how we work have been observed. Working from home is not an option for everyone. At work it may be difficult to keep social distance, which may lead to fear and anxiety of being infected with SARS-CoV-19 or of spreading the virus.Objectives:To explore frequency of anxiety and concerns related to work in patients with inflammatory rheumatic diseases(IRD) during the COVID-19 pandemic and to identify patient and disease characteristics associated with increased anxiety.Methods:Patients in routine care followed in the nationwide Danish DANBIO registry were invited to answer an on-line questionnaire regarding current rheumatic disease activity, behavior and anxiety including current work-status and -concerns. Responses were linked to patient data previously recorded in DANBIO. Clinical factors associated with work-related concerns (completely/mostly agree versus neither/nor, completely/mostly disagree) were explored with multivariable logistic regression.Results:Among 14,758 respondents (38% of eligible patients), 5,950 patients (40%) were currently working (60% full time/31% part time/9% self-employed) (61% female, 53% rheumatoid arthritis/19% psoriatic arthritis/20% axial spondyloarthritis/9% other). Although 68% reported that the workplace helped to make necessary interventions, work-related concerns and anxiety were frequent. Thus, 22% found it difficult (completely/mostly agree) to keep physical distance at work and 20% were worried about going to work (Figure 1).Factors associated with concerns about going to work were female gender, longer education, other chronic conditions, biological therapy, and higher (=poorer) EQ-5D, whereas diagnosis was without significance. Similar patterns were found for other work-related concerns (not shown).Conclusion:In this cohort of &gt;5,000 patients with inflammatory rheumatic diseases followed in a nationwide registry, during the COVID-19 pandemic anxiety and concerns related to the work situation were frequent, especially in women and patients treated with biologicals, with other chronic diseases and with poor quality of life.

Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial

ObjectivesIn 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....

Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model.

Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with that in the general population and, second, to develop a simple clinical prediction model and to obtain risk estimates for individual patients. This was a matched-cohort study based on nationwide registries in Denmark. Patients with RA, axial SpA and PsA initiating first bDMARD monitored in the DANBIO registry were matched 1:10 by age, gender and postal code with controls from the general population. The risk of serious infection during 12 months' follow-up was assessed with Cox regression. Prediction models were developed using logistic regression and compared using area under the receiver operating characteristic curve (AUC). We included 11372 patients and 113715 controls. During follow-up, 522 patients (4.6%) and 1434 controls (1.3%) developed a serious infection (hazard ratio 3.7, 95% CI 3.4, 4.1). Age-stratified risk was largely similar across diagnoses. A simple prediction model, the 'DANBIO infection risk score', based on age and a count of six clinical risk factors had moderate discriminative power (internal validation: AUC 0.69) that was comparable to that of the existing RABBIT (Rheumatoide Arthritis Beobachtung der BIologika-Therapie) Risk Score (external validation: AUC 0.68). Patients with inflammatory joint diseases initiating bDMARD treatment had a four times increased risk of serious infection compared with the general population. A simple prediction model, feasible for shared decision-making, was developed to obtain risk estimates for individual patients.

Self-protection strategies and health behaviour in patients with inflammatory rheumatic diseases during the COVID-19 pandemic: results and predictors in more than 12 000 patients with inflammatory rheumatic diseases followed in the Danish DANBIO registry

AimsIn Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and...

NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium

This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2rs11574851T allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA− = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2TT haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2rs1056890 SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2rs1005044C allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.

Overall infection risk in rheumatoid arthritis during treatment with abatacept, rituximab and tocilizumab; an observational cohort study.

Most infections in patients with RA are treated in primary care with antibiotics. A small fraction require hospitalization. Only a few studies exist regarding the overall risk of infection (i.e. prescription of antibiotics or hospitalization due to infection) in patients initiating non-TNF-inhibitor therapy. In Danish RA patients initiating abatacept, rituximab and tocilizumab treatment in routine care, the aims were to compare adjusted incidence rates (IR) of infections and to estimate relative risk of infections across the drugs during 0-12 and 0-24 months. This was an observational cohort study including all RA patients in the DANBIO registry starting a non-TNF-inhibitor from 2010 to 2017. Infections were defined as a prescription of antibiotics or hospitalization due to infection. Prescriptions, comorbidities and infections were captured through linkage to national registries. IRs of infections (age, gender adjusted) and rate ratios (as estimates of RR (relative risk)), adjusted for additional covariates) (Poisson regression) were calculated. We identified 3696 treatment episodes (abatacept 1115, rituximab 1017, tocilizumab 1564). At baseline, rituximab users were older and had more previous cancer. During 0-12 months, 1747 infections occurred. Age and gender-adjusted IRs per 100 person-years were as follows: abatacept: 76 (95% CI: 69, 84); rituximab: 87 (95% CI: 79, 96); tocilizumab: 77 (95% CI: 71, 84). Adjusted RRs were 0.94 (95% CI: 0.81, 1.08) for abatacept and 0.94 (95% CI: 0.81, 1.03) for tocilizumab compared with rituximab and 1.00 (95% CI: 0.88, 1.14) for abatacept compared with tocilizumab. RRs around 1 were observed after 24 months. Switchers and ever smokers had higher risk compared with biologic-naïve and never smokers, respectively. Overall infections were common in non-TNF-inhibitor-treated RA patients, with a tendency towards rituximab having the highest risk, but CIs were wide in all analyses. Confounding by indication may at least partly explain any differences.

Validation and assessment of minimally clinically important difference of the unadjusted Health Assessment Questionnaire in a Danish cohort: uncovering ordinal bias

Objectives: The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a widely used patient-reported outcome for functional disability in rheumatoid arthritis (RA). Minimal clinically important differences (MCIDs) in the HAQ-DI were previously calculated based on device-corrected ordinal HAQ-DI scores, leading to limited generalizability and validity for today’s patients. Our objectives were to examine the internal construct validity of the unadjusted HAQ-DI and to determine an MCID in a cohort of Danish RA patients based on the transformed linear logit scale of the HAQ-DI.Method: The study included 362 RA patients registered in the DANBIO registry. The Rasch model was fitted to HAQ-DI data at baseline and after 3 months’ follow-up. MCID was calculated as the median changes in the original HAQ-DI score and logit HAQ-DI score in those patients who had experienced minimal improvement (15–30 mm on a 0–100 mm Patient Global scale).Results: HAQ-DI data showed acceptable fit to the Rasch model at both time-points, and consistent item ranking across time indicated instrument invariance. Sixty-one patients (16.8%, ~1/6) had an improvement above the MCID on the logit scale but improvement below the MCID on the original scale, while the opposite was not the case for any patients.Conclusions: The Danish unadjusted version of the HAQ-DI showed acceptable internal construct validity. Application of the logit MCID classified an additional one in six patients as having achieved an MCID compared to the MCID calculated on the ordinal scale, which may have potential implications for the powering of future studies.

Does a mandatory non-medical switch from originator to biosimilar etanercept lead to increase in healthcare use and costs? A Danish register-based study of patients with inflammatory arthritis

ObjectivesIn year 2016, Danish national guidelines included a mandatory switch of patients with inflammatory rheumatic diseases treated with originator etanercept (ETA) to biosimilar SB4 in routine care. We aimed to...

To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry

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...