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ObjectiveTo explore anxiety and self-isolation in patients with inflammatory rheumatic disease (IRD)15 months into the coronavirus disease 2019 (COVID-19) pandemic, including attitudes toward and effects of SARS-CoV-2 vaccination.MethodsA nationwide online survey was conducted at 3 timepoints: May 2020, November 2020, and May 2021. Patients with IRD followed in the Danish Rheumatology Quality Registry (DANBIO) were asked about the effects of the pandemic, including SARS-CoV-2 infection and their behavior, anxiety, and concerns. The May 2021 survey included attitudes toward SARS-CoV-2 and influenza vaccination. Characteristics associated with self-isolation in May 2021 were explored with adjusted logistic regression analyses that included patient characteristics and SARS-CoV-2 vaccination status.ResultsRespondents to surveys 1, 2, and 3 included 12,789; 14,755; and 13,921 patients, respectively; 64% had rheumatoid arthritis and 63% were female. Anxiety and concerns were highest in May 2020 and decreased to stable levels in November 2020 and May 2021; 86%, 50%, and 52% of respondents reported self-isolation, respectively. In May 2021, 4% of respondents self-reported previous SARS-CoV-2 infection. The SARS-CoV-2 vaccine acceptance rate was 86%, and the proportion of patients vaccinated against influenza had increased from 50% in winter 2019-2020 to 64% in winter 2020-2021. The proportion of patients with anxiety appeared similar among those vaccinated and unvaccinated against SARS-CoV-2. In multivariable analyses, being unvaccinated, female gender, receiving biologic drugs, and poor quality of life were independently associated with self-isolation.ConclusionLevels of anxiety and self-isolation decreased after the initial lockdown period in patients with IRD. Half of the patients reported self-isolation in May 2021, a phase that included widespread reopening of society and large-scale vaccination. The lack of prepandemic data prevented a full understanding of the long-term effects of the pandemic on anxiety and self-isolation in patients with IRD.

Objectives 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. Methods 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. Results 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. Conclusion 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.

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), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).MethodsObservational 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.ResultsOf 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.ConclusionThis 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.

Objectives To 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. Methods Patients 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). Results We 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%). Conclusion In 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.

Key messages #### What is already known about this subject? #### What does this study add? #### How might this impact on clinical practice or future developments? COVID-19 is a pandemic that has shattered the world, not only once, but with a second wave swiping across the continents. Patients with inflammatory rheumatic diseases (IRDs) have encountered widespread shielding (ie, stringent self-isolation) and poor quality of life (QoL).1–3 Work obligations could potentially affect opportunities to self-isolate. The World Health Organization has expressed concerns that some workers may be at higher risk of developing severe COVID-19 illness because of age or pre-existing medical conditions.4 Despite being a topic on the political agenda, in social media and patient organisations, surprisingly little is known regarding the impact of the ongoing pandemic on anxiety and concerns related to the work situation, and in a review of the medical literature, we found no previous research publications regarding patients with IRD. We performed a nationwide online survey in patients with IRD (rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and other)1 routinely followed in the Danish DANBIO registry.5 In October–November 2020, patients were invited to answer questions regarding the impact of the …

ObjectivesPatients’ first-hand experiences of faecal microbiota transplantation (FMT) performed in a rheumatological care setting have yet to be elucidated. The objectives were to explore participants’ perceptions of being part of an FMT trial thereby identifying potential trial participation effects and enlightening the patient perspective on the outlook for future FMT trials in rheumatic diseases.DesignIn a qualitative study nested within a double-blind, randomised, placebo-controlled trial (RCT) testing FMT as a potential new antirheumatic treatment, semistructured telephone interviews were conducted following the trial participants’ final 26-week visit. Qualitative researchers, who did not take part in the main trial, performed the interviews and the primary analysis. The experiences explored related to the conduct of the RCT and changes in the participants’ everyday life. The analysis was carried out using a thematic approach.SettingA Danish rheumatology university outpatient clinic with nationwide inclusion.ParticipantsThe study included 10 patients with psoriatic arthritis (PsA) who were unaware of their treatment allocation (FMT/sham transplantation) and completed the final 26-week trial visit.ResultsParticipation in the RCT influenced the patients’ understanding of PsA and induced positive changes in their everyday life. Renewed hopes for the future in addition to a feeling of enhanced care contributed to significant trial participation effects. FMT was deemed a tolerable and safe treatment.ConclusionsDiscrepancies between the clinical and the research setting should be considered when discussing the clinical relevance of the results of the RCT. Overall, patients with PsA who have participated in an RCT testing FMT find the treatment acceptable and safe encouraging more research into the field of microbiota-targeted interventions in rheumatic diseases.Trial registration numberNCT03058900; Pre-results.

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 again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation.MethodsPatients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses.ResultsWe included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation.ConclusionIn >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients’ anxiety and self-isolation is important during this and potential future epidemics.

ObjectivesAlthough causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).MethodsIn this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.ResultsOf 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).ConclusionsIn this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.Trial registration numberNCT03058900.

Background: In the DANBIO quality registry in Denmark, patients with rheumatoid arthritis (RA) psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) have reported Patient Reported Outcomes (PROs) including the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) for nearly twenty years as part of routine care. Patients’ feedback have stressed a need for a shorter registration of disability (1). While the shorter Multidimensional Health Assessment Questionnaire (MDHAQ) is preferred by patients, the original HAQ-DI is the preferred tool in observational studies. Thus, a conversion algorithm between the MDHAQ and HAQ-DI scores is warranted.Objectives: To develop and validate a simple conversion algorithm between MDHAQ and HAQ-DI scores in RA, PsA and axSpA patients.Methods: Patients registered in DANBIO with a diagnosis of RA, PsA or axSpA who had completed both HAQ-DI and MDHAQ simultaneously at a visit +/- 30 days from start of conventional synthetic (cs)DMARD or biological (b)DMARD were eligible for the analysis, and randomly divided into development and validation cohorts stratified by diagnosis. The conversion algorithm was developed in the RA development cohort using linear regression with HAQ-DI as the dependent variable and MDHAQ as the independent variable. The predicted HAQ (pHAQ) scores were then calculated by applying the conversion algorithm to the MDHAQ scores in the RA, PsA and axSpA validation cohorts. The pHAQ was validated against the HAQ-DI in the validation cohorts regarding criterion, correlational and construct validity.Results: We included 8983/4410/1760 patients with RA/PsA/axSpA, respectively. The conversion algorithm pHAQ=0.15+MDHAQ*1.08 had the best fit (R2=0.83) in the RA development cohort.Criterion validity: The correlation coefficients between HAQ-DI/pHAQ and patient global score at baseline were 0.66/0.65. In groups of patients with high and low disability (defined as patient global score ≥50), standardized mean difference was -1.4 for HAQ-DI, and -1.4 for pHAQ.Correlational validity: Correlation coefficients between HAQ-DI/pHAQ and ΔHAQ-DI/ΔpHAQ between baseline and first follow-up visit were r=0.91 and r=0.87, respectively. Correlation coefficients between HAQ-DI/pHAQ and pain score, DAS28CRP and physician global score were 0.63/0.64, 0.55/0.55 and 0.34/0.34, respectively. A Bland-Altman plot showed good agreement of HAQ-DI and pHAQ across all functional states.Construct validity: HAQ-DI/pHAQ at the first follow-up visit after baseline was comparable between Patient Acceptable Symptom State groups (PASS=No: mean 1.17 vs 1.18/PASS=Yes: 0.55 vs 0.60). Similar results were seen for the external anchor (Figure 1).In PsA and axSpA validation cohorts, similar results were found.Conclusion: A conversion algorithm from MDHAQ to HAQ-DI was developed in ≈ 4500 RA patients. In separate large validation cohorts of RA, PsA and axSpA patients, the predicted HAQ calculated from the MDHAQ scores showed good criterion, correlational and construct validity comparable to the original HAQ-DI. The results suggest that for research purposes the MDHAQ can be converted to HAQ-DI if a full HAQ-DI has not been performed.References: [1] Primdahl J. et al. Arthritis Care Res 2019 (in press).Acknowledgments: The authors thank all Danish patients and Departments of Rheumatology, who conscientiously report to the DANBIO registry.Disclosure of Interests: Elisabeth Svensson: None declared, Katja Løngaard: None declared, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Rikke Meincke: None declared, Jens Kristian Pedersen: None declared, Lene Dreyer: None declared, Niels Steen Krogh: None declared, Dorte Vendelbo Jensen: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis

We thank McGonagle et al 1 for their insightful comments on our manuscript on faecal microbiota transplantation (FMT) in active peripheral psoriatic arthritis (PsA), known as the FLORA trial.2 We agree that the clinical findings of this first double-blind, randomised, trial of FMT in immune-mediated arthritis warrant further investigation into the underlying biological mechanisms coupling gut composition, the intestinal barrier–microbiotal interaction, and systemic inflammation in PsA and related chronic inflammatory diseases. Indeed, evidence linking the composition of the gut microbiota and initiation/progression of immune-mediated disease is limited and is primarily derived from animal models.3 Suggested mechanisms encompass failure to induce immunological tolerance,4 which may direct the T cell repertoire towards a pro-inflammatory phenotype including Th17 differentiation and activation seen in PsA, loss of epithelial integrity5 and systemic translocation due to local inflammation and/or tissue damage that may enable trafficking of both activated immune cells and antigenic material to distant sites thereby creating perpetual systemic inflammatory stimuli6 by epitope spreading,7 bystander activation8 and/or molecular mimicry.9 …

Background:Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel therapeutic option for treatment of extra-intestinal inflammatory diseases.1Objectives:In this proof-of-concept study, we evaluated efficacy and safety of FMT in psoriatic arthritis (PsA).2Methods:In this double-blind, parallel-group, sham-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. The transplants (50 g faeces) came from one of four healthy, thoroughly screened, anonymous stool donors.3 The primary efficacy endpoint was the proportion of participants experiencing treatment failure (i.e., needing treatment intensification) through 26 weeks. The first key secondary endpoint was change in Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to week 26. Safety was monitored throughout the trial. Trial registration number: NCT03058900, ClinicalTrials.gov.Results:Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT), all received the assigned intervention, and 30 (97%) completed the 26-week clinical evaluation (Table 1). Treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI, 1.06 to 9.62; P=0.018). During the entire 26 weeks of observation, the rate of the treatment failures was significantly higher in the FMT than in the sham group, see figure 1. Improvement in HAQ-DI score differed between groups (0.07 vs 0.30) by 0.23 points (95% CI, 0.02 to 0.44; P=0.031) in favour of sham. No serious adverse events were observed.Conclusion:In this first interventional randomised controlled trial of FMT in immune-mediated arthritis, FMT was inferior to sham in treating active peripheral PsA. FMT did not appear to result in serious adverse events.Figure 1.Time-to-event curves by intervention group from baseline to week 26. FMT, faecal microbiota transplantation.Table 1.Baseline demographics and disease characteristics.CharacteristicFMT(n=15)Sham(n=16)Female sex, no. (%)8 (53%)12 (75%)Age, yr.48.9 (16.1)52.4 (11.0)Height, cm175.2 (7.0)169.8 (8.6)Weight, kg93.6 (15.4)92.4 (24.8)Time since diagnosis, yr.a2.6 (0.3 to 5.8)5.6 (0.5 to 8.8)Rheumatoid factor IgM negative, no. (%)b13 (93%)15 (94%)Anti-citrullinated peptide antibody negative, no. (%)b14 (100%)16 (100%)HLA-B27 negative, no. (%)15 (100%)13 (81%)C-reactive protein, mg/L4.98 (7.18)5.54 (5.87)HAQ-DI0.89 (0.51)0.78 (0.50)Swollen joint 66 count7.5 (3.0)6.7 (2.7)Tender joint 68 count14.9 (8.9)17.3 (8.8)SPARCC enthesitis index Score ≥1, no. (%)13 (87%)15 (94%) Score in patients with a score ≥18.1 (4.3)7.2 (3.3)Data are mean (SD) or n (%) unless otherwise stated. FMT, faecal microbiota transplantation. a Time since diagnosis of psoriatic arthritis is presented as median and interquartile range (IQR). b Presence of rheumatoid factor (IgM) and anti-citrullinated peptide antibody was not accessed in one patient from the FMT group.References:[1]Manasson J, Blank RB, Scher JU. The microbiome in rheumatology: Where are we and where should we go? Ann Rheum Dis 2020;79:727-33.[2]Kragsnaes MS, Kjeldsen J, Horn HC, et al. Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial. BMJ Open 2018;8:e019231.[3]Kragsnaes MS, Nilsson AC, Kjeldsen J, et al. How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service? Transfusion 2020;60:1135-41.Acknowledgements:We thank all participants for their contribution. We thank CS Klinkby, trial nurse, for assistance in relation to the conduct of the trial visits. We also thank L Albjerg, biomedical laboratory technologist, AC Nilsson, consultant, KF Rasmussen, consultant, and J Georgsen, consultant, at the Department of Clinical Immunology, Odense University Hospital, Denmark, for assisting in the implementation of the FMT stool bank.Disclosure of Interests:Maja Skov Kragsnaes Grant/research support from: Novartis 2017 (unrestricted research grant) to support 3 months PhD salary related to the conduct of the trial., Jens Kjeldsen: None declared, Hans Christian Horn: None declared, Heidi Lausten Munk: None declared, Jens Kristian Pedersen: None declared, Søren Andreas Just: None declared, Palle Ahlquist: None declared, Finn Moeller Pedersen: None declared, Maarten de Wit: None declared, Sören Möller: None declared, Vibeke Andersen: None declared, Karsten Kristiansen: None declared, Hanne Marie Holt: None declared, Dorte Kinggaard Holm: None declared, Robin Christensen: None declared, Torkell Ellingsen Grant/research support from: Novartis 2017 (unrestricted research grant)

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:In the DANBIO quality registry in Denmark, patients with rheumatoid arthritis (RA) psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) have reported Patient Reported Outcomes (PROs) including the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) for nearly twenty years as part of routine care. Patients’ feedback have stressed a need for a shorter registration of disability (1). While the shorter Multidimensional Health Assessment Questionnaire (MDHAQ) is preferred by patients, the original HAQ-DI is the preferred tool in observational studies. Thus, a conversion algorithm between the MDHAQ and HAQ-DI scores is warranted.Objectives:To develop and validate a simple conversion algorithm between MDHAQ and HAQ-DI scores in RA, PsA and axSpA patients.Methods:Patients registered in DANBIO with a diagnosis of RA, PsA or axSpA who had completed both HAQ-DI and MDHAQ simultaneously at a visit +/- 30 days from start of conventional synthetic (cs)DMARD or biological (b)DMARD were eligible for the analysis, and randomly divided into development and validation cohorts stratified by diagnosis. The conversion algorithm was developed in the RA development cohort using linear regression with HAQ-DI as the dependent variable and MDHAQ as the independent variable. The predicted HAQ (pHAQ) scores were then calculated by applying the conversion algorithm to the MDHAQ scores in the RA, PsA and axSpA validation cohorts. The pHAQ was validated against the HAQ-DI in the validation cohorts regarding criterion, correlational and construct validity.Results:We included 8983/4410/1760 patients with RA/PsA/axSpA, respectively. The conversion algorithm pHAQ=0.15+MDHAQ*1.08 had the best fit (R2=0.83) in the RA development cohort.Criterion validity: The correlation coefficients between HAQ-DI/pHAQ and patient global score at baseline were 0.66/0.65. In groups of patients with high and low disability (defined as patient global score ≥50), standardized mean difference was -1.4 for HAQ-DI, and -1.4 for pHAQ.Correlational validity: Correlation coefficients between HAQ-DI/pHAQ and ΔHAQ-DI/ΔpHAQ between baseline and first follow-up visit were r=0.91 and r=0.87, respectively. Correlation coefficients between HAQ-DI/pHAQ and pain score, DAS28CRP and physician global score were 0.63/0.64, 0.55/0.55 and 0.34/0.34, respectively. A Bland-Altman plot showed good agreement of HAQ-DI and pHAQ across all functional states.Construct validity: HAQ-DI/pHAQ at the first follow-up visit after baseline was comparable between Patient Acceptable Symptom State groups (PASS=No: mean 1.17 vs 1.18/PASS=Yes: 0.55 vs 0.60). Similar results were seen for the external anchor (Figure 1).In PsA and axSpA validation cohorts, similar results were found.Conclusion:A conversion algorithm from MDHAQ to HAQ-DI was developed in ≈ 4500 RA patients. In separate large validation cohorts of RA, PsA and axSpA patients, the predicted HAQ calculated from the MDHAQ scores showed good criterion, correlational and construct validity comparable to the original HAQ-DI. The results suggest that for research purposes the MDHAQ can be converted to HAQ-DI if a full HAQ-DI has not been performed.References:[1] Primdahl J. et al. Arthritis Care Res 2019 (in press).Acknowledgments:The authors thank all Danish patients and Departments of Rheumatology, who conscientiously report to the DANBIO registry.Disclosure of Interests:Elisabeth Svensson: None declared, Katja Løngaard: None declared, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Rikke Meincke: None declared, Jens Kristian Pedersen: None declared, Lene Dreyer: None declared, Niels Steen Krogh: None declared, Dorte Vendelbo Jensen: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis

Background:The incidence of depression is about 1.5-2 times higher in patients with rheumatoid arthritis (RA) versus controls. (1, 2) Previous data on treatment with antidepressants has pointed to an almost equal distribution of indications between depression and other indications. (3)Objectives:To describe and compare indications and the incidence of treatment with antidepressants in patients with RA and matched controls.Methods:The study involved an inception cohort of patients with incident RA ascertained from 1995 to 2002 according to the American College of Rheumatology 1987 classification criteria (4) and randomly drawn, population controls with the same age, sex, and area of residence (ratio 1:5). Indications on redeemed prescriptions were included in the Danish National Prescription Register from 2004 and we collected data on all prescriptions for antidepressants (Anatomical Therapeutic Classification code N06A) and counted person-years (PY) at risk from 01.01.2004 to 31.12.2017, death, or migration. The incidence of first treatment was evaluated as defined daily dose (DDD) for two definitions of exposure (DDD>0, DDD>178) within one calendar year together with the positive indication depression after one year of run-in.Results:The current analyses involved 431 RA patients and 2167 controls (median age at inclusion: 59 years, 70% females; RA patients: 20% erosive, 74% rheumatoid factor positive). The most frequent indication for treatment with antidepressants was depression (Table 1).Table 1.Indication on prescriptions for antidepressants, % (95% confidence interval (CI))Rheumatoid arthritis (n=6,955)Controls(n=33,740)Depressive disorders62.3 (61.2-63.5)62.7 (62.2-63.2)Anxiety disorders5.4 (4.9-6.0)3.9 (3.7-4.1)Nervous system medications6.5 (5.9-7.1)6.8 (6.6-7.1)Other indications0.2 (0.0-0.3)0.2 (0.2-0.2)No or missing indications25.6 (24.6-26.7)26.3 (25.9-26.8)There were no significant differences in the incidence of treatment with the indication depression in patients versus controls(Table 2).Table 2.Incidence rate ratio for treatment with antidepressantsDDD>0DDD>178Rheumatoid arthritis (Events/PY)Controls (Events/PY)Incidence rate ratio (95% CI)Rheumatoid arthritis (Events/PY)Controls (Events/PY)Incidence rate ratio (95% CI)Overall98/3,720471/19,2291.08(0.86-1.34)73/3,893339/20,3381.13 (0.87-1.46)SexFemales79/2,616354/13,4601.15 (0.89-1.47)61/2,753264/14,2991.20 (0.89-1.59)Males19/1,104117/5,7690.85 (0.49-1.39)12/1,14175/6,0390.85 (0.42-1.57)Age15-345/17524/9621.15 (0.34-3.07)4/18821/1,0221.04 (0.26-3.07)35-443/52231/2,3490.44 (0.85-1.40)3/52420/2,5010.72 (0.14-2.42)45-5414/73164/3,8711.16 (0.60-2.09)10/77340/4,1221.33 (0.59-2.71)55-6425/1,198128/6,2001.01 (0.63-1.56)17/1,25384/6,4981.05 (0.58-1.78)65-7437/849158/4,5981.27 (0.86-1.82)28/892120/4,8741.28 (0.81-1.94)75+14/24666/1,2481.08 (0.56-1.94)11/26554/1,3211.02 (0.48-1.97)Conclusion:The main indication for prescribing antidepressants in patients with RA was depression. Patients with RA were not exposed to antidepressants more often than controls. This could be due to prescription bias or reflect pertinent choice of treatment in patients with RA.References:[1]Wang SL, et al. PLoS One 2014;9:e107791.[2]Marrie RA, et al. Arthritis Care Res 2018;70:970-8.[3]Wong J, et al. JAMA 2016;315:2230-2.[4]Pedersen JK, et al. Scand J Rheumatol 2018;47:371-7.Acknowledgments:The study was supported by the Danish Rheumatism AssociationDisclosure of Interests:None declared

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

Objectives: To investigate mortality and its predictors in a retrospectively defined population-based rheumatoid arthritis (RA) inception cohort Method: We included patients ascertained with incident RA from a region in the southern part of Denmark from 1995 to 2002. All patients fulfilled the 1987 American College of Rheumatology criteria for RA. The patients were followed from RA classification until death, emigration, or end of follow-up on 31 December 2013. We used personal record linkage with national public registers to obtain information on education, employment, cohabitation, comorbidity, and vital status. Results: The cohort comprised 509 patients, of whom 200 (39%) died during 6079 person-years. The most frequent underlying causes of death were cardiovascular disease (34%), neoplasms (26%), and respiratory disease (12%). In rheumatoid factor (RF)-positive males, the standardized mortality ratio (95% confidence interval) from all causes was 1.47 (1.15–1.88), from cardiovascular disease 1.63 (1.09–2.46), from respiratory disease 2.03 (1.06–3.90), and from neoplasms 2.26 (1.02–5.03) in the age group < 70 years, and 2.45 (1.23–4.90) in the age group > 79 years. On applying Cox models after multiple imputations by chained equations, we found that RF modified the effect of age. Employment status, comorbidity, and gender were independent baseline predictors of subsequent mortality. Conclusion: In this cohort, significant excess mortality was confined to RF-positive males. The effect of age was modified by RF, and employment status and comorbidity were independent predictors of mortality.

Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic Resonance Imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmuno assay (Orion Diagnostica, Finland). One-hundred-and-nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 μg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 μg/l [2.6;4.9], p=0.05) and controls (3.8 μg/l [3.0;4.8], p

Objective.To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status).Methods.Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm].Results.The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27–negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55–84)/65 mm (48–77); global: 76 mm (62–88)/68 mm (50–80); fatigue: 74 mm (55–85)/67 mm (50–80); and BASDAI: 64 (54–77)/59 (46–71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3–17)/11 mg/l (5–22); and BAS Metrology Index: 20 (10–40)/40 (20–50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15–2.02) versus 3.67 years (2.86–4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29–2.36), AS: HR 2.04 (1.53–2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05).Conclusion.In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.

OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect.METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods.RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups.CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.

A 69-year-old female was admitted due to progressive loss of muscle strength following addition of fluconazole to long-term simvastatin treatment. Rhabdomyolysis was suspected and both drugs were discontinued. Forced diuresis was initiated together with a short course of prednisolone. After 21 weeks the patient had regained normal muscle strength and endurance. The favourable course and the absence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase suggest that the condition was due to interaction between the two drugs, which are both metabolized via the CYP3A4 pathway.

Objective.To study the association between polymorphisms in the mannose-binding lectin gene (MBL2)and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA).Methods.Patients with early RA (n = 158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion forMBL2pooled structural genotypes (O/O, A/O, A/A), regulatoryMBL2promoter polymorphism in position −221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score).Results.Eight patients were homozygousMBL2defective (O/O), 101 belonged to an intermediate group, and 49 wereMBL2high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p = 0.02), and physical disability by HAQ (p = 0.01) were associated with highMBL2expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs.Conclusion.The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

We estimated the incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001. At a rheumatology hospital serving a population of about 200 000 people over the age of 15, medical records were scrutinized. As case definition we used the tree and list format of 1987 American College of Rheumatology criteria for rheumatoid arthritis. The mean annual incidence rate per 100 000 person years was 40 in females, 21 in males, and 31 in females and males combined. The incidence of rheumatoid arthritis in Denmark is in accordance with recent studies from North America, the UK, and Northern European countries. The aetiology of rheumatoid arthritis is unknown but this study indicates that in these populations the exposure to non-genetic host and environmental aetiological factors is similar.

OBJECTIVES: The aim of this study was to measure, in early rheumatoid arthritis (RA) patients, the concentration of CC-chemokine ligand 19 (CCL19) in plasma and the cell-surface expression of CC-chemokine receptor 7 (CCR7) on circulating monocytes and CD4+ T lymphocytes and to analyse correlations with disease activity and 5-year radiographic progression.METHOD: In disease-modifying anti-rheumatic drug (DMARD)-naïve RA patients (disease duration < 6 months), we measured plasma CCL19 by enzyme-linked immunosorbent assay (ELISA) (n = 160) and CCR7 cell-surface expression on monocytes and CD4+ T lymphocytes by flow cytometry (n = 40) at baseline and after 1 year of treatment with methotrexate (MTX) or methotrexate+cyclosporin A (MTX/CyA). Radiographic progression was scored by the van der Heijde-modified Total Sharp Score (TSS) from 0 to 5 years.RESULTS: Increased baseline CCL19 (median 85 pg/mL, range 31-1008 pg/mL, p = 0.01) decreased after 1 year (median 31 pg/mL, range 31-1030 pg/mL, p < 0.001) and 5 years (median 31 pg/mL, range 31-247 pg/mL, p < 0.001) to a level below the controls (n = 45) (median 60 pg/mL, range 31-152 pg/mL). Baseline plasma CCL19 levels [p = 0.011, 95% confidence interval (CI) 0.0030-0.0176], anti-cyclic citrullinated peptide (anti-CCP) antibody status (p = 0.002, 95% CI 0.61-2.38), and TSS > 0 at baseline (p < 0.001, 95% CI 1.21-3.16) were independent predictors of 5-year radiographic progression evaluated by multiple logistic regression in contrast to never smoked, C-reactive protein (CRP), gender, age, number of tender (NTJ) and swollen joints (NSJ), and 28-joint Disease Activity Score (DAS28). Increased CCR7 expression on monocytes (p = 0.008) correlated to CRP (p = 0.006, r = 0.52) and normalized (n = 15) after 1 year (p = 0.02).CONCLUSIONS: In DMARD-naïve RA patients, CCL19 plasma level and CCR7 surface expression on monocytes were upregulated and normalized after 1 year of treatment. Increased baseline plasma CCL19 level, anti-CCP antibody status, and TSS > 0 at baseline correlated independently with 5-year radiographic progression. OBJECTIVES: The aim of this study was to measure, in early rheumatoid arthritis (RA) patients, the concentration of CC-chemokine ligand 19 (CCL19) in plasma and the cell-surface expression of CC-chemokine receptor 7 (CCR7) on circulating monocytes and CD4+ T lymphocytes and to analyse correlations with disease activity and 5-year radiographic progression.METHOD: In disease-modifying anti-rheumatic drug (DMARD)-naïve RA patients (disease duration < 6 months), we measured plasma CCL19 by enzyme-linked immunosorbent assay (ELISA) (n = 160) and CCR7 cell-surface expression on monocytes and CD4+ T lymphocytes by flow cytometry (n = 40) at baseline and after 1 year of treatment with methotrexate (MTX) or methotrexate+cyclosporin A (MTX/CyA). Radiographic progression was scored by the van der Heijde-modified Total Sharp Score (TSS) from 0 to 5 years.RESULTS: Increased baseline CCL19 (median 85 pg/mL, range 31-1008 pg/mL, p = 0.01) decreased after 1 year (median 31 pg/mL, range 31-1030 pg/mL, p < 0.001) and 5 years (median 31 pg/mL, range 31-247 pg/mL, p < 0.001) to a level below the controls (n = 45) (median 60 pg/mL, range 31-152 pg/mL). Baseline plasma CCL19 levels [p = 0.011, 95% confidence interval (CI) 0.0030-0.0176], anti-cyclic citrullinated peptide (anti-CCP) antibody status (p = 0.002, 95% CI 0.61-2.38), and TSS > 0 at baseline (p < 0.001, 95% CI 1.21-3.16) were independent predictors of 5-year radiographic progression evaluated by multiple logistic regression in contrast to never smoked, C-reactive protein (CRP), gender, age, number of tender (NTJ) and swollen joints (NSJ), and 28-joint Disease Activity Score (DAS28). Increased CCR7 expression on monocytes (p = 0.008) correlated to CRP (p = 0.006, r = 0.52) and normalized (n = 15) after 1 year (p = 0.02).CONCLUSIONS: In DMARD-naïve RA patients, CCL19 plasma level and CCR7 surface expression on monocytes were upregulated and normalized after 1 year of treatment. Increased baseline plasma CCL19 level, anti-CCP antibody status, and TSS > 0 at baseline correlated independently with 5-year radiographic progression.

Background Magnetic Resonance Imaging (MRI) osteitis and synovitis have been identified as predictors of structural damage progression in rheumatoid arthritis (RA)1,2, but the predictive value of MRI joint space narrowing (JSN, a measure of cartilage damage) and tenosynovitis (TS) needs further investigation. Objectives To investigate the predictive value of baseline MRI inflammatory and damage parameters on 2 year MRI and X-ray damage progression in an early RA (eRA) cohort following a non biologic treat-to-target strategy. Methods In 129 eRA ( Results Independent predictors of structural damage progression are presented in table 1. If MRI JSN was not included in the model, MRI osteitis score was statistically significant independent predictor of X-ray progression (coefficient 0.32, p=0.001, vs TSS progression). Conclusions This trial is the first to report that MRI JSN independently predicts both X-ray and MRI damage progression in early RA. Further studies are needed to confirm early MRI-determined cartilage damage as predictor of progressive joint destruction in RA. References Hetland et al, Ann Rheum Dis 2009 Boyesen et al, Ann Rheum Dis 2011 Haavardsholm et al, Ann Rheum Dis 2007 Disclosure of Interest None declared

Background Little is known about tumor-necrosis-factor-alpha-inhibitor (TNFi) treatment outcomes in Ankylosing Spondylitis (AS) vs. non-radiographic axial spondyloartrhitis (nr-axSpA). Objectives To compare baseline disease activity and treatment outcomes in biologic naive patients with AS and nr-axSpA, who initiate TNFi treatment in clinical practice taking potential confounders into consideration. Methods We performed an observational cohort study based on prospectively registered data in the nationwide Danish quality registry, DANBIO, including baseline and 3–6 months9 follow-up markers of disease activity (visual analogue score (VAS) global disease, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BAS metrology index (BASMI) and serum C-reactive protein (CRP)). Treatment response was defined as either a 50% or a 20 mm reduction in BASDAI after 3–6 mths treatment. We used Kaplan-Meier plots, Cox and logistic regression analyses to study the impact of diagnosis (AS vs. nr-axSpA) and potential confounders (gender, age, start year, HLA-B27, disease duration, TNFi type, smoking, baseline disease activity) on TNFi adherence and response. Numbers are medians (IQR) unless otherwise stated. Results We identified 1,250 TNFi naive patients in DANBIO with axSpA according to the treating physician. Of these, 50% had AS, 28% nr-axSpA and 21% lacked X-rays of sacroiliac joints. Baseline demographics and disease activity differed in nr-axSpA vs. AS (Table). Response rates were similar, but treatment adherence was poorer in nr-axSpA than in AS (univariate, Table). In confounder adjusted analyses, axSpA sub-diagnosis was not associated with response rates or treatment adherence. However, HLA-B27 positivity was associated with better treatment adherence (HLA-B27 neg/pos, nr-axSpA: HR 1.74 (1.29–2.36), AS: HR 2.04 (1.53–2.71.), both p Conclusions In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at the start of the first TNFi treatment but had similar confounder adjusted treatment adherences and response as AS pts. HLA-B27 positive pts had better outcomes irrespective of axSpA sub-diagnosis. Disclosure of Interest B. Glintborg: None declared, I. Juul Sorensen: None declared, M. Ostergaard: None declared, A. A. Mahamoud: None declared, N. S. Krogh: None declared, L. Andersen: None declared, J. Raun: None declared, O. Hendricks: None declared, M. Kowalski: None declared, L. Danielsen: None declared, S. Christensen: None declared, N. al Chaer: None declared, R. Pelck: None declared, H. Nordin: None declared, J. Pedersen: None declared, D. Kraus: None declared, I. Jensen Hansen: None declared, J. Espesen: None declared, A. Schlemmer: None declared, A. Loft Speakers bureau: MSD, L. Salomonsen: None declared, L. Dreyer: None declared, M. Hetland: None declared

Background Patients with rheumatoid arthritis (RA) from hospital-based series have an increased mortality, in particular from cardiovascular diseases. Estimates of standardized mortality ratios (SMR) from population-based inception cohorts have been inconsistent and mortality in RA patients may be modified by treatment and preventive strategies. Furthermore, human senescence in the general population has been delayed since 1950.(1) We therefore wanted to investigate the all-cause SMR in a Danish population-based inception RA cohort from the late pre-biologic era seen at a regional hospital with documented focus on intention-to-treat (2, 3) and cardiovascular screening (4). Objectives To investigate SMR in an unselected inception cohort of Danish RA patients from 1995 to 2002. Methods The case base was the population of the County of South Jutland according to the Danish Civil Registration System (CVR). Incident RA cases were identified at the referral center for rheumatic diseases in the County where the observed completeness of registrations from the case base was 97%.(5) The registry was scrutinized for all RA patients fulfilling the 1987 American College of Rheumatology criteria for RA from 1995 to 2002. Linkage of cases to CVR and the Danish Register of Causes of Death was based on unique personal identification numbers. Cases were followed from inclusion until emigration, death or end of follow-up (31.12.2013). Statistics Denmark provided mortality rates for the total Danish population from 1995 to 2013. Results A total of 509 cases were identified (Females 68%; mean age 61 years; rheumatoid factor positive 77%; erosive 23%). During 6079 person-years (py) of follow-up 200 (39%) patients had died (Females 32%; males 55%). The main causes of death are seen in table 1. There were no statistically significant differences in the causes of death according to sex (Chi-squared test=12.2, degrees of freedom: 7, p=0.092). The median follow-up time was 13 years and the average mortality rate 33/1000 py (Females 26/1000 py; males 50/1000 py). The overall SMR was 1.04 (95%>confidence interval (CI): 0.91–1.19), in females 0.96 (95%>CI: 0.79–1.43) and in males 1.16 (95%>CI: 0.95–1.43). Conclusions In this population-based study there were no significant excess mortality compared to the general population. The predominant causes of death were cardiovascular-, neoplastic- and pulmonary disease. References Vaupel JW. Nature 2010;464(7288):536–42. Hetland ML, et al. Arthritis Rheum. 2006 May;54(5):1401–9. Horslev-Petersen K, et al. Ann Rheum Dis. 2014 Apr;73(4):654–61. Primdahl J, el al. Ann Rheum Dis. 2013 Nov;72(11):1771–6. Pedersen JK, et al. Rheumatol Int 2009;29(4):411–5. Acknowledgement Supported by the Region of Southern Denmark and the Danish Rheumatism Association. Disclosure of Interest None declared

Objective To investigate the short-term and long-term efficacy of intra-articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthritis (RA). Methods During 2 years of follow-up in the CIMESTRA trial, 160 patients received intra-articular betamethasone in up to four swollen joints/visit in combination with disease-modifying antirheumatic drugs. Short-term efficacy was assessed by EULAR good response. Long-term efficacy by Kaplan–Meier plots of the joint injection survival (ie, the time between injection and renewed flare). Potential predictors of joint injection survival were tested. Results 1373 Unique joints (ankles, elbows, knees, metacarpophalangeal (MCP), metatarsophalangeal, proximal interphalangeal (PIP), shoulders, wrists) were injected during 2 years. 531 Joints received a second injection, and 262 a third. At baseline, the median numbers of injections (dose of betamethasone) was 4 (28 mg), declining to 0 (0 mg) at subsequent visits. At weeks 2, 4 and 6, 50.0%, 58.1% and 61.7% had achieved a EULAR good response. After 1 and 2 years, respectively, 62.3% (95% CI 58.1% to 66.9%) and 55.5% (51.1% to 60.3%) of the joints injected at baseline had not relapsed. All joint areas had good 2-year joint injection survival, longest for the PIP joints: 73.7% (79.4% to 95.3%). 2-Year joint injection survival was higher for first injections: 56.6% (53.7% to 59.8%) than for the second: 43.4% (38.4% to 49.0%) and the third: 31.3% (25.0% to 39.3%). Adverse events were mild and transient. A high MRI synovitis score of MCP joints and anti-CCP-negativity were associated with poorer joint injection survival, whereas IgM-RF and C-reactive protein were not. Conclusion In early RA, intra-articular injections of betamethasone in small and large peripheral joints resulted in rapid, effective and longlasting inflammatory control. The cumulative dose of betamethasone was low, and the injections were well tolerated.

Objective.Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.Methods.A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.Results.Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.Conclusion.Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.

The aim of the present study was to estimate the prevalence of rheumatoid arthritis in the southern part of Denmark. Using a screening questionnaire, telephone interview, register data, and a clinical examination cases were ascertained from a random sample of 4995 individuals over the age of 15. As case definition we used the original and modified 1987 American College of Rheumatology classification criteria. The overall point prevalence was 0.26% (95% confidence interval: 0.13-0.39) in the total sample and 0.35% (95% confidence interval: 0.17-0.52) among the responders; the cumulative prevalence was 0.75% (95% confidence interval: 0.52-0.97) in the total sample and 0.92% (95% confidence interval: 0.62-1.21) among the responders. The cumulative prevalence was higher than in other studies combining the results of a survey with register data. The point prevalence was underestimated due to low participation rate in the clinical examination and remission among the participants.

Udgivelsesdato: 2010-May-5 OBJECTIVE: /st> At 5 years' follow-up of early ( 139 patients completed 5 years' follow-up with maintained double-blinding and a strict synovitis suppressive treatment strategy with intra-articular betamethasone injections (intra-articular glucocorticosteroid (GC)) and escalation of disease-modifying anti-rheumatic drug treatment. Disease activity, total Sharp-van der Heijde Score (TSS) of hands, wrists and forefeet were assessed at baseline and after 3, 4 and 5 years. MRI of the wrist and anti-cyclic citrullinated peptide (anti-CCP) were assessed at baseline. RESULTS: /st> At 5 years, TSS progression rate was Early and strict synovitis suppressive treatment with MTX and intra-articular GC lead to high remission rates and halting of erosive progression at 5 years. No additional effect of initial combination therapy with CSA was found. The results parallel those reported for tumour necrosis factor alpha antagonists. Baseline MRI-bone oedema, TSS and anti-CCP predicted radiographic progression.

Objective.To investigate the relationship between markers of collagen II synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naïve to disease-modifying antirheumatic drugs.Methods.One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years. The N-terminal propeptide of collagen IIA (PIIANP) and the cross-linked C-telopeptide of collagen II (CTX-II) were quantified at baseline by ELISA. PIIANP was also assayed at 2 and 4 years. Anticyclic citrullinated peptide (anti-CCP) was recorded at baseline. An uncoupling index for cartilage collagen metabolism was calculated from PIIANP and CTX-II measurements.Results.PIIANP was low at diagnosis and 4 years on (p < 0.001), irrespective of treatment and disease activity. PIIANP was lowest in anti-CCP positive patients (p = 0.006), and there was a negative correlation between PIIANP and anti-CCP titers (ρ = −0.25, p 0.002). CTX-II was increased (p < 0.001) and correlated positively with disease activity and radiographic progression, but not with anti-CCP (p = 0.93). The uncoupling index was not superior to CTX-II in predicting radiographic changes.Conclusion.These results suggest that cartilage collagen formation and degradation are unbalanced when RA is diagnosed. The different associations of collagen II anabolism (PIIANP) and collagen II degradation (CTX-II) with anti-CCP, synovitis, and radiographic progression indicate that at this early stage of RA, cartilage collagen degradation is mainly driven by synovitis, while anti-CCP antibodies may interfere with cartilage regeneration by inhibiting collagen IIA formation. Trial registration j.nr NCT00209859.

Udgivelsesdato: 2009 The aim of this study was to describe the mean incidence rate of rheumatoid arthritis over a 7-year period from 1995 to 2001 in a population in the southern part of Denmark, using the data from several sources. Cases fulfilling the 1987 American College of Rheumatology criteria for rheumatoid arthritis were identified at hospitals and private practising rheumatologists (referral centres), and in general practice. The observed incidence was 32/100,000 person-years (95% confidence interval 29-35). Using the ratio between the number of cases known only from general practice and the number known from general practice and referral centres, the estimated incidence was 35/100,000 person-years (95% confidence interval 32-38). We suggest that the estimated rate should be viewed as a plausible upper limit for the incidence of rheumatoid arthritis in the southern part of Denmark.

Background MRI has been shown to be more sensitive than clinical examination and x-ray for detection of inflammatory and destructive joint changes in early rheumatoid arthritis (RA) and to discriminate between treatment arms in clinical trials using the semi-quantitative Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI scoring (RAMRIS) system. Objectives To investigate whether MRI-determined measures of disease activity and joint destruction were suppressed in very early RA patients following a treat-to-target strategy with methotrexate (MTX) and intraarticular (i.a.) betamethasone and to investigate whether concomitant cyclosporine (CYA) had an additional effect on MRI determined inflammatory and destructive findings over 2 years. Methods In the 2-year randomised, double-blind, multicentre, clinical, treat-to-target trial, CIMESTRA, 160 patients with early ( Results MRI-results from the wrist-only group are shown in table 1. The data in the wrist+MCP group were overall similar (data not shown). No statistically significant differences between the treatment groups were observed in any MRI characteristics at baseline or at any follow-up time point. Both the wrist-only group and the wrist+MCP group showed significant reductions compared to baseline in osteitis, synovitis and tenosynovitis at 6 months (all parameters) and 12 and 24 months (synovitis and tenosynovitis). Statistically significant, but numerically low, increases in erosion and JSN scores from baseline to 6, 12 and 24 months were seen. Conclusions A treat-to-target strategy with MTX and i.a. betamethasone reduced MRI inflammatory findings significantly, with no additional effect of CYA, but minor structural damage progression was still observed. References Hetland ML, et al. 2006. Arthritis Rheum 54:1401-1409. Hetland ML, et al. 2009. Ann Rheum Dis 68:384-390. Disclosure of Interest None declared

Fibroblastic rheumatism (FR) is a rare disorder of unknown cause first described in 1980.1 We here report the first Scandinavian patient with FR. A 55 year old Danish woman was referred to our department in July 2000 with a 2½ year history of pain in the proximal interphalangeal (PIP) joints, knees, and ankles. The pain worsened over night and upon exercise. On examination, the right knee and the second PIP joint on the left hand were tender and swollen. The other PIP joints and both wrists were tender. On both hands there were several pink, 3–10 mm, tender and mobile skin nodules (fig 1), and a 20 mm nodule under the left foot. Figure 1 Skin nodules adjacent to the second metacarpophalangeal, distal interphalangeal, and third PIP joints on the right hand. All laboratory investigations were normal, …

BACKGROUND: The aim of the present study was to evaluate the accuracy of two approaches using magnetic resonance imaging (MRI) or combined ultrasonography (US) and anti-cyclic citrullinated peptide antibody (ACPA) for diagnosis and classification of individuals with established rheumatoid arthritis (RA).METHODS: In 53 individuals from a population-based, cross-sectional study, historic fulfilment of the American College of Rheumatology (ACR) 1987 criteria ("classification") or RA diagnosed by a rheumatologist ("diagnosis") were used as standard references. The sensitivity, specificity and Area under Curve for Receiver Operating Characteristics curves (ROC-area: (sensitivity + specificity)/2) were calculated for "current fulfilment of the ACR 1987 criteria" (list format), "adapted ACR 1987 criteria" (list format, substituting IgM rheumatoid factor with ACPA and clinical joint swelling and erosions on radiography with synovitis and erosions detected by US on a semi-quantitative scale), and RA MRI scoring System (RAMRIS) scores on low-field MRI in the unilateral hand.RESULTS: For the ACR 1987 criteria the ROC-area was 75% (sensitivity/specificity = 50%/100%) (with "classification" as standard reference) and 69% (44%/94%) (with "diagnosis" as standard reference), while for the adapted ACR 1987 criteria it was 86% (75%/97%) (classification) and 82% (72%/91%) (diagnosis). For RAMRIS synovitis score in metacarpophalangeal (MCP) joints only (cut-off ≥5), the ROC-area (sensitivity/specificity) was 78% (62%/94%) (classification) and 85% (69%/100%) (diagnosis), while for the total synovitis score of MCP joints plus wrist (cut-off ≥10) it was 78% (62%/94%) (both classification and diagnosis).CONCLUSIONS: Compared with the ACR 1987 criteria, low-field MRI alone or adapted criteria incorporating US and ACPA increased the correct classification and diagnosis of RA. BACKGROUND: The aim of the present study was to evaluate the accuracy of two approaches using magnetic resonance imaging (MRI) or combined ultrasonography (US) and anti-cyclic citrullinated peptide antibody (ACPA) for diagnosis and classification of individuals with established rheumatoid arthritis (RA).METHODS: In 53 individuals from a population-based, cross-sectional study, historic fulfilment of the American College of Rheumatology (ACR) 1987 criteria ("classification") or RA diagnosed by a rheumatologist ("diagnosis") were used as standard references. The sensitivity, specificity and Area under Curve for Receiver Operating Characteristics curves (ROC-area: (sensitivity + specificity)/2) were calculated for "current fulfilment of the ACR 1987 criteria" (list format), "adapted ACR 1987 criteria" (list format, substituting IgM rheumatoid factor with ACPA and clinical joint swelling and erosions on radiography with synovitis and erosions detected by US on a semi-quantitative scale), and RA MRI scoring System (RAMRIS) scores on low-field MRI in the unilateral hand.RESULTS: For the ACR 1987 criteria the ROC-area was 75% (sensitivity/specificity = 50%/100%) (with "classification" as standard reference) and 69% (44%/94%) (with "diagnosis" as standard reference), while for the adapted ACR 1987 criteria it was 86% (75%/97%) (classification) and 82% (72%/91%) (diagnosis). For RAMRIS synovitis score in metacarpophalangeal (MCP) joints only (cut-off ≥5), the ROC-area (sensitivity/specificity) was 78% (62%/94%) (classification) and 85% (69%/100%) (diagnosis), while for the total synovitis score of MCP joints plus wrist (cut-off ≥10) it was 78% (62%/94%) (both classification and diagnosis).CONCLUSIONS: Compared with the ACR 1987 criteria, low-field MRI alone or adapted criteria incorporating US and ACPA increased the correct classification and diagnosis of RA.

Udgivelsesdato: 2010-Mar-8 ABSTRACT: INTRODUCTION: Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA. METHODS: One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed. RESULTS: Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings. CONCLUSIONS: This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation. TRIAL REGISTRATION: (j.nr NCT00209859).