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Spondyloarthritis may contribute to deficits in cognition. The objective of this study was to compare cognitive abilities in patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) with matched reference groups. This investigator-initiated, cross-sectional, exploratory study of adults with axSpA or PsA was conducted at two German rheumatology centres (November 2018-September 2019). All data on patient and disease characteristics and cognitive abilities were collected at a single visit. Cognitive function was assessed by the previously validated Memory and Attention Test subscores of selective attention, episodic working memory, and episodic short-term memory and compared with subscores from healthy age-, sex-, and education-matched reference subjects. The mean patient age was 51.1 and 55.8 years in the axSpA (n = 101) and PsA (n = 117) groups, respectively, and mean symptom duration was 13.7 and 10.3 years. Compared with matched reference subjects, axSpA and PsA patients showed significant impairments in selective attention (mean difference of -6.5 and -4.5, respectively, on a 45-point scale; P 0.001 for both) and no significant differences in episodic working memory. The PsA cohort, but not the axSpA cohort, had significantly better episodic short-term memory subscores compared with matched reference subjects (mean change of 2.0 on a 15-point scale; P 0.001). Explorative subgroup analyses were unable to identify factors influencing cognitive changes, including disease activity, pain, and function, but may have been underpowered. We conclude that impairments in selective attention may impact the ability of axSpA and PsA patients to process information. These findings warrant additional studies, including longitudinal analyses, in patients with spondyloarthritis.

Summary Background Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms. Methods RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score ClinicalTrials.gov ( NCT02779114 ). Findings Between May 26, 2010, and May 29, 2018, 303 patients were enrolled and allocated to continue (n=100), taper (n=102), or stop DMARDs (n=101). 282 (93%) of 303 patients were analysed (93 [93%] of 100 for continue, 93 [91%] of 102 for taper, and 96 [95%] of 101 for stop). Remission was maintained at 12 months by 81·2% (95% CI 73·3–90·0) in the continue group, 58·6% (49·2–70·0) in the taper group, and 43·3% (34·6–55·5) in the stop group (p=0·0005 with log-rank test for trend). Hazard ratios for relapse were 3·02 (1·69–5·40; p=0.0003) for the taper group and 4·34 (2·48–7·60; p Interpretation Reducing antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, with maintenance of remission occurring in about half of the patients. Because relapse rates were significantly higher in patients who tapered or stopped antirheumatic drugs than in patients who continued with a 100% dose, such approaches will require tight monitoring of disease activity. However, remission was regained after reintroduction of antirheumatic treatments in most of those who relapsed in this study. These results might help to prevent overtreatment in a substantial number of patients with rheumatoid arthritis. Funding None.

PurposeKidney transplantation (KT) is the treatment of choice for end-stage chronic kidney disease (CKD) and is well known to improve the clinical outcome of patients. However, the impact of KT on comorbid psychological symptoms, particularly depression and anxiety, is less clear, and recipients of living-donor (LD) organs may have a different psychological outcome from recipients of dead-donor (DD) organs.Design/methodology/approachIn total, 152 patients were included and analyzed using a cross-sectional design. Of these patients, 25 were pre-KT, 13 were post-KT with a LD transplant and 114 were post-KT with a DD transplant. The patients were tested for a variety of psychometric outcomes using the Hospital Anxiety and Depression Scale, the 12-Item Short Form Health Survey (assessing physical and mental health-related quality of life), the Resilience Scale, the Coping Self-Questionnaire and the Social Support Questionnaire.FindingsThe mean age of the patients was 51.25 years and 40 per cent of the patients were female. As expected, the post-KT patients had significantly better scores on the physical component of the Short Form Health Survey than the pre-KT patients, and there were no significant differences between the two post-KT groups. There were no significant differences among the groups in any of the other psychometric outcome parameters tested, including anxiety, depression and the mental component of health-related quality of life.Research limitations/implicationsKT and the origin of the donor organ do not appear to have a significant impact on the psychological well-being of transplant patients with CKD. Although the diagnosis and early treatment of psychological symptoms, such as depression and anxiety, remain important for these patients, decisions regarding KT, including the mode of transplantation, should not be fundamentally influenced by concerns about psychological impairments at the population level.Originality/valueCKD is a serious condition involving profound impairment of the physical and psychological well-being of patients. KT is considered the treatment of choice for most of these patients. KT has notable advantages over dialysis with regard to the long-term physical functioning of the renal and cardiovascular system and increases the life expectancy of patients. However, the data on the improvement of psychological impairments after KT are less conclusive.

Treatments used for rheumatoid arthritis (RA) are under investigation for their efficacy to prevent RA in at risk groups. It is therefore important to understand treatment preferences of those at risk. We systematically reviewed quantitative preference studies of drugs to treat, or prevent RA, to inform the design of further studies and trials of RA prevention. Stated preference studies for RA treatment or prevention were identified through a search of five databases. Study characteristics and results were extracted, and the relative importance of different types of treatment attributes was compared across populations. Twenty three studies were included 20 of RA treatments (18 of patients; 2 of the general public) and 3 prevention studies with first-degree relatives (FDRs). Benefits, risks, administration method and cost (when included) were important determinants of treatment choice. A benefit was more important than a risk attribute in half of the studies of RA treatment that included a benefit attribute and 2/3 studies of RA prevention. There was variability in the relative importance of attributes across the few prevention studies. In studies with non-patient participants, attributes describing confidence in treatment effectiveness/safety were more important determinants of choice than in studies with patients. Most preference studies relating to RA are of treatments for established RA. Few studies examine preferences for treatments to prevent RA. Given intense research focus on RA prevention, additional preference studies in this context are needed. Variation in treatment preferences across different populations is not well understood and direct comparisons are needed.

Objective To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. Methods A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit–risk trade-offs and predicted treatment uptake was subsequently calculated. Results Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. Conclusion Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics.

ObjectivesTo quantify tolerance to risks of preventive treatments among first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA).MethodsPreventive treatments for RA are under investigation. In a preference survey, adult FDRs assumed a 60% chance of developing RA within 2 years and made choices between no treatment and hypothetical preventive treatment options with a fixed level of benefit (reduction in chance of developing RA from 60% to 20%) and varying levels of risks. Using a probabilistic threshold technique, each risk was increased or decreased until participants switched their choice. Perceived risk of RA, health literacy, numeracy, Brief Illness Perception Questionnaire and Beliefs about Medicines Questionnaire-General were also assessed. Maximum acceptable risk (MAR) was summarised using descriptive statistics. Associations between MARs and participants’ characteristics were assessed using interval regression with effects coding.Results289 FDRs (80 male) responded. The mean MAR for a 40% reduction in chance of developing RA was 29.08% risk of mild side effects, 9.09% risk of serious infection and 0.85% risk of a serious side effect. Participants aged over 60 years were less tolerant of serious infection risk (mean MAR ±2.06%) than younger participants. Risk of mild side effects was less acceptable to participants who perceived higher likelihood of developing RA (mean MAR ±3.34%) and more acceptable to those believing that if they developed RA it would last for a long time (mean MAR ±4.44%).ConclusionsAge, perceived chance of developing RA and perceived duration of RA were associated with tolerance to some risks of preventive RA therapy.

Real-world data are crucial to continuously improve the management of patients with rheumatic and musculoskeletal diseases (RMDs). The German RheumaDatenRhePort (RHADAR) registry encompasses a network of rheumatologists and researchers in Germany providing pseudonymized real-world patient data and allowing timely and continuous improvement in the care of RMD patients. The RHADAR modules allow automated anamnesis and adaptive coordination of appointments regarding individual urgency levels. Further modules focus on the collection and integration of electronic patient-reported outcomes in between consultations. The digital RHADAR modules ultimately allow a patient-centered adaptive approach to integrated medical care starting as early as possible in the disease course. Such a closed-loop system consisting of various modules along the whole patient pathway enables comprehensive and timely patient management in an unprecedented manner.

Real-world data are crucial to continuously improve the management of patients with rheumatic and musculoskeletal diseases (RMDs). The German RheumaDatenRhePort (RHADAR) registry encompasses a network of rheumatologists and researchers in Germany providing pseudonymized real-world patient data and allowing timely and continuous improvement in the care of RMD patients. The RHADAR modules allow automated anamnesis and adaptive coordination of appointments regarding individual urgency levels. Further modules focus on the collection and integration of electronic patient-reported outcomes in between consultations. The digital RHADAR modules ultimately allow a patient-centered adaptive approach to integrated medical care starting as early as possible in the disease course. Such a closed-loop system consisting of various modules along the whole patient pathway enables comprehensive and timely patient management in an unprecedented manner.

IntroductionAmidst growing consensus that stakeholder decision-making during drug development should be informed by an understanding of patient preferences, the Innovative Medicines Initiative project ‘Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle’ (PREFER) is developing evidence-based recommendations about how and when patient preferences should be integrated into the drug life cycle. This protocol describes a PREFER clinical case study which compares two preference elicitation methodologies across several populations and provides information about benefit–risk trade-offs by those at risk of rheumatoid arthritis (RA) for preventive interventions.Methods and analysisThis mixed methods study will be conducted in three countries (UK, Germany, Romania) to assess preferences of (1) first-degree relatives (FDRs) of patients with RA and (2) members of the public. Focus groups using nominal group techniques (UK) and ranking surveys (Germany and Romania) will identify and rank key treatment attributes. Focus group transcripts will be analysed thematically using the framework method and average rank orders calculated. These results will inform the treatment attributes to be assessed in a survey including a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT). The survey will also include measures of sociodemographic variables, health literacy, numeracy, illness perceptions and beliefs about medicines. The survey will be administered to (1) 400 FDRs of patients with RA (UK); (2) 100 FDRs of patients with RA (Germany); and (3) 1000 members of the public in each of UK, Germany and Romania. Logit-based approaches will be used to analyse the DCE and imputation and interval regression for the PTT.Ethics and disseminationThis study has been approved by the London-Hampstead Research Ethics Committee (19/LO/0407) and the Ethics Committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg (92_17 B). The protocol has been approved by the PREFER expert review board. The results will be disseminated widely and will inform the PREFER recommendations.

Objective.To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)–tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission.Methods.The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates.Results.RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83.Conclusion.Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.

Eosinophils were reported to serve as an essential component of the plasma cell niche within the bone marrow. As the potential contribution of eosinophils to humoral immunity has remained incompletely understood, we aimed to further characterize their role during antibody responses and to additionally investigate their role in autoimmune disease. Contrary to our expectations and the currently prevailing paradigm, we found that eosinophils are fully dispensable for the survival of murine bone marrow plasma cells and accordingly do not contribute to antibody production and autoantibody-mediated disease. Littermate wild type and eosinophil-deficient ΔdblGATA-1 animals showed similar numbers and frequencies of plasma cells and did not differ in steady state levels of immunoglobulins or their ability to raise antigen-specific antibody responses. Eosinophils were likewise dispensable for autoantibody production or autoantibody-induced disease in a mouse model of systemic lupus erythematosus. Our findings thus argue against a role of eosinophils during the maintenance of the plasma cell pool and challenge the hitherto postulated concept of an eosinophil-sustained bone marrow niche.

Background:There is increasing research focus on intervention for rheumatoid arthritis (RA) at the earliest stages of disease development, including treatment to prevent RA in at-risk groups. Novel cellular therapies are in development, and the effectiveness of existing immunomodulatory agents to prevent RA in those at risk is under investigation. Quantitative evidence of likely uptake of preventive treatments, and preferences for benefits and risks of such treatments is limited.Objectives:To quantify preferences for preventive therapies for RA.Methods:A web-based survey (n = 2959) was administered to an age- and gender- stratified sample of adults in the general population from online survey panels in the UK, Germany, and Romania. After receiving information about RA, questions to check comprehension of background information, an introduction to the survey tasks and warm-up questions, participants were asked to imagine that they were experiencing arthralgia (without swelling) and had positive autoantibody tests indicating a 60% chance of developing RA in the next two years. Using a discrete choice experiment with a Bayesian D-efficient design, participants were offered a series of 15 choices between no treatment and two unlabeled hypothetical treatments to lower risk of RA development. Treatments were defined by six attributes with varying levels including benefits, risks, and frequency/route of administration (Table 1). One choice task with fixed levels described treatments representative of those under investigation for RA prevention (abatacept, hydroxychloroquine, atorvastatin and tolerogenic cell-based therapy). Attribute selection and presentation was informed by previous qualitative research, ranking surveys, systematic literature review, and expert opinion. Survey design was informed by patient research partners. The survey was pre-tested during qualitative interviews and revised. A pilot of the final survey with 100 respondents was conducted to obtain priors for the final experimental design. Random parameters logit (RPL) models were used to estimate relative importance of treatment attributes and likely treatment uptake rates in each country.Table 1.Treatment attributes and levelsAttributeLevelsChance of developing RA reduced from 60% to10%; 20%; 30%; 40%How the treatment is takenA shallow injection under the skinA drip into the veinOne or two tabletsHow often the medication has to be takenDailyWeeklyMonthlyEvery 6 monthsChance of mild side effects2%; 5%; 10%Chance of a serious infection due to treatment0%; 1%; 5%Chance of a serious side effect that is potentially irreversible1 in 100,000 people20 in 100,000 people100 in 100,000 peopleResults:Across all three countries, effectiveness was the treatment attribute that had most impact on treatment choice (Figure 1). Method of administration was second most important for respondents from the UK and Romania but less important for German respondents. Risks of serious infection and serious side effects were more important determinants of treatment choice for respondents in Romania than they were in the UK and Germany. Percentage choice of fixed profiles reflecting abatacept, atorvastatin, hydroxychloroquine, tolerogenic cell-based therapy and no treatment differed across countries (χ2=78.90; pConclusion:This study suggests that effective preventive treatments for RA are acceptable to members of the general population told to assume up a 60% chance of developing RA. The relative importance of treatment attributes and likely uptake of fixed treatment profiles differed across countries. These findings are informative for the design of prevention trials, and the development of informational resources and efficient preventive strategies for those at risk of developing RA.Acknowledgements:On behalf of the PREFER project. PREFER received funding from the IMI 2 Joint Undertaking (grant No. 115966), which receives support from the EU’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA). K. Raza is supported by the NIHR Birmingham Biomedical Research Centre.Disclosure of Interests:Gwenda Simons: None declared, Jorien Veldwijk: None declared, Rachael Di Santostefano Shareholder of: Johnson & Johnson, Employee of: Janssen R&D (of Johnson & Johnson), Matthias Englbrecht Speakers bureau: AbbVie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Mundipharma, Paid instructor for: AbbVie, Chugai, Roche, Consultant of: AbbVie, Novartis, Roche, Sanofi, Grant/research support from: Roche, Chugai, Christine Radawski Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, Larissa Valor: None declared, Karim Raza Consultant of: Personal fees from Abbvie, Pfizer, Sanofi, Lilly, Bristol Myers Squibb, UCB, Janssen, and Roche Chugai, Grant/research support from: Abbvie and Pfizer, M. Falahee: None declared

Background:There is some evidence that neuropsychiatric changes occur in systemic lupus(1) and rheumatoid arthritis(2). However, little is known regarding a possible disease-related impairment of cognitive abilities in axial spondyloarthritis (axSpA).Objectives:To evaluate patients with axSpA regarding cognitive impairments.Methods:Patients with axSpA attending two rheumatology practices were routinely evaluated by rheumatologists and underwent a computer-based memory and attention test (MAT) (3, 4) with subscale scores ranging from 0 (worst) to 15 (best). The results of short-term memory and working memory were compared to an age-, sex- and education-matched control group of healthy subjects. Descriptive results are presented as median (IQR) for interval data and n (%) for nominal data if not stated otherwise. Two-tailed Wilcoxon signed-rank tests including Bonferroni-Holm adjustment for multiple tests were conducted to investigate the magnitude of potential differences in cognitive abilities.Results:101 consecutive patients were tested (Table 1). After multiple testing adjustment for two subscales, Wilcoxon signed-rank tests returned significant findings for working memory (V = 539.5, p = 0.006, |r| = 0.204) but not for short-term memory (V = 1075, p = 0.351, |r| = 0.078). Regarding the scales’ anchors, descriptive results on pairwise differences suggested axSpA patients to have working memory scores that are on average 10.7% lower compared to control participants (mean Δ= -1.64, SD Δ= 5.95).Table 1.Patients and disease characteristicsn%MeanSDMedian25% Quantile75% QuantileAge10110051.111.6524260Age (female)4847.552.611.75444.561Age (male)5352.549.811.5514157< 13 years formal education4746.5≥ 13 years formal education5453.5HLA B27 positive n/N64/9263.4Disease duration (years)10110013.711.712421Disease duration (female, years)4847.511.69.99417.2Disease duration (male, years)5352.515.512.915523BASDAI9291.13.71.73.82.45BASFI9190.132.42.31.24.5BASMI7574.31.92.3103ASDAS98972.30.82.31.82.8Conclusion:The MAT computerized testing is a feasible test and was well accepted by patients. Results regarding working memory suggest that cognitive abilities needed to accomplish everyday tasks may be impaired in axSpA patients. Further work is needed to characterise possible causes of or associations with this cognitive impairment.References:[1]Zabala A, Salgueiro M, Saez-Atxukarro O, Ballesteros J, Ruiz-Irastorza G, Segarra R. Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis. J Int Neuropsychol Soc. 2018:1-11.[2]Vitturi BK, Nascimento BAC, Alves BR, de Campos FSC, Torigoe DY. Cognitive impairment in patients with rheumatoid arthritis. J Clin Neurosci. 2019;69:81-7.[3]Adler G, Bektas M, Feger M, Lembach Y. [Computer-based assessment of memory and attention: evaluation of the memory and attention test (MAT)]. Psychiatr Prax. 2012;39(2):79-83.[4]Adler G, Lembach Y. Memory and selective attention in multiple sclerosis: cross-sectional computer-based assessment in a large outpatient sample. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):439-43.Acknowledgements:This study was funded by the RHADAR GbR (A Network of Rheumatologists), Bahnhofstr. 32, 82152 Planegg, Germany. RHADAR GbR has received a grant for this study from Novartis Pharma GmbH.Disclosure of Interests:Stefan Kleinert Consultant of: Novartis, Abbvie, Grant/research support from: Novartis, Praxedis Rapp: None declared., Florian Schuch Speakers bureau: Novartis, Abbvie, Gilead, Consultant of: Novartis, Abbvie, Gilead, Monika Ronneberger: None declared., Joerg Wendler Speakers bureau: Roche, Pharma, JanssenCilag, Novartis, Abbvie, Consultant of: JanssenCilag, Patrizia Sternad: None declared., Florian Popp: None declared., Peter Bartz-Bazzanella: None declared., Cay-Benedict von der Decken: None declared., Kirsten Karberg Speakers bureau: Roche, Sanofi, Abbvie, Lilly, Georg Gauler Speakers bureau: Abbvie, Gilead, Novartis, Lilly, Consultant of: Lilly, Gilead, Abbvie, Patrick Wurth Speakers bureau: Abbvie, Lilly, UCB, Medac, Susanna Spaethling-Mestekemper Speakers bureau: Abbvie, BMS, Celgene, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Christoph Kuhn: None declared., Matthias Englbrecht Speakers bureau: AbbVie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Mundipharma, Paid instructor for: AbbVie, Chugai, Roche, Consultant of: AbbVie, Novartis, Roche, Sanofi, Grant/research support from: Roche, Chugai, Wolfgang Vorbrüggen: None declared., Georg Adler: None declared., Martin Welcker Speakers bureau: Abbvie, Actelion, Amgen, Biogen,BMS, Berlin Chemie, Celgene, Galapagos, Gilead, GSK, Hexal, Janssen, Medac, MSD, Mundipharma, Mylan, Novartis, Pfizer, Roche, Sanofi, SOBI, UCB, Grant/research support from: Novartis, Abbvie.

BackgroundFever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET).MethodsProspective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT.Results240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still’s disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001).Conclusion18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.

Objective: To characterize the specific structural properties of the erosion-prone bare area of the human joint and to search for early microstructural changes in this region during rheumatoid arthritis Methods: An initial cadaveric study was used for exact localization of the bare area of the metacarpal heads, detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral computed tomography (HR-pQCT) and, after anatomical dissection, their validation by micro-computed tomography (μCT). In the second part, number and distribution of CoMiCs were analyzed in 105 healthy individuals and 107 RA patients with similar sex and age distribution. Results: HR-pQCT investigation combined with adaptive thresholding allowed detection of CoMiCs in the bare area of cadaveric joints. Their existence in the bare area was additionally validated by μCT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly (p

Background Psoriasis (PsO) and psoriatic arthritis (PsA) differentially impact patients’ quality of life (QoL) due to pain, mental changes in the context of chronic inflammation and impaired physical function. Effective anti-inflammatory therapy has shown to be effective to improve QoL in PsO and PsA patients. However, the impact of ant-inflammatory therapy on QoL may be different in the earliest stages of PsA as compared to established disease. Objectives To perform a detailed comparative investigation of the effect of interleukin (IL)-17 inhibition with 300 mg secukinumab (SEC) on QoL in patients with very early PsA/pre-PsA and established PsA. Methods Patients from the IVEPsA study (1) on very early PsA/pre-PsA (N=20) and the PSARTROS (2) study on established PsA (N=20) were longitudinally assessed for SF-36, DLQI, PsAID and HAQ-DI at baseline and after 4, 12 and 24 weeks. All patients received SEC treatment; 19/20 pre-PsA patients and 17/20 established PsA patients completed the study. Changes from baseline values were evaluated using linear mixed effects models adjusted for baseline values of each scale, gender, age and disease duration, and plotted as model coefficients and respective 95% confidence intervals that represent adjusted mean absolute improvement from baseline. Scale signs were inverted as necessary to ease interpretability. Further subgroup analysis was conducted using Mann-Whitney. Results Significant and rapid improvements were observed in both pre-PsA and established PsA treated with SEC with regard to pain (SF-36 bodily pain, BP), general health perception (GH), dermatology quality of life index (DLQI) and PsA impact of disease (PsAID), as well as in the SF-36 component scores (mental component score of SF-36, MCS and physical component score of SF-36, PCS). Physical function- oriented instruments like SF-36 physical functioning (PF), role limitation due to physical problem (RP) and HAQ-DI were preferentially affected in established PsA group due to the higher functional burden of disease (Figure). There were more differences with respect to the course of QoL improvements through week 12 and 24, as established PsA patients showed an incremental improvement in SF-36 BP, PF and GH from week 12 to 24 while most of the responses plateaued in the pre-PsA group. Furthermore, established PsA patients who achieved minimal disease activity showed a significantly higher improvement in PsAID, HAQ-DI, SF-36 PF, RP and BP (all p Conclusion Pain, mental health, general health perception and impact of disease rapidly improve in both very early PsA/pre-PsA and established PsA patients treated with SEC. These data support the concept that very early treatment of PsA leads to significant improvement in QoL with the additional benefit of prevention of bone damage as previously shown (1, 2). References [1] OP0305 Disease interception in psoriasis patients with subclinical joint inflammation by interleukin 17 inhibition with secukinumab – data from a prospective open label study. Kampylafka et al, aRD June 2018, Volume 77, Suppl. 2 [2] Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study. Kampylafka et al, arthritis Res ther. 2018Jul27;20(1):153 Acknowledgement This study was supported by an unrestricted grant from Novartis. Disclosure of interests Eleni Kampylafka: None declared, Matthias Englbrecht Grant/research support from: Roche Pharma aG, Chugai Pharma Europe Ltd., Consultant for: Roche Pharma aG, Chugai Pharma Europe Ltd., abbVie Deutschland GmbH & Co. KG, Celgene GmbH, Lilly Deutschland GmbH, Speakers bureau: Roche Pharma aG, Chugai Pharma Europe Ltd., abbVie Deutschland GmbH & Co. KG, Celgene GmbH, Lilly Deutschland GmbH, Koray Tascilar: None declared, Veronika Lerchen: None declared, Christina Linz: None declared, arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: abbvie, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi aventis, and UCB (in total more than $10,000), Georg Schett: None declared, axel Hueber Grant/research support from: Novartis, Pfizer, Consultant for: Lilly, Speakers bureau: Lilly, Novartis, Janssen, abbvie

Background Patients with rheumatic diseases have a high prevalence of depressive symptoms that affect the patients’ self-assessment, adherence to medication [1], and mortality [2]. Objectives To evaluate patients with rheumatic diseases regarding depressive symptoms by using the PHQ-2 (Patient Health Questionnaire with 2 items) and assess its feasibility during routine clinical practice. Methods 485 consecutive patients with rheumatic diseases attending a rheumatology practice that is part of the public health care system in Erlangen, Germany underwent a routine clinical assessment by different rheumatologists. In addition to disease-specific assessments and questionnaires, every patient answered two questions regarding depressive symptoms which form the PHQ-2 (range of 0[best] to 6[worst]). All questionnaires were answered digitally by touchscreen and Software RheumaDok and RheumaDokM (Nils Korber und Joachim Elgas G.b.R). A PHQ-2 score ≥ 3 points has a sensitivity of 87% and a specificity of 78% for detecting a major depressive disorder compared to a structured clinical interview. [3] A positive screening result was either addressed during subsequent medical consultation or by notifying the patient’s general practitioner. The PHQ-2 is a short form of the PHQ-9 which previously had been validated in rheumatoid arthritis. [4]. Results Overall, 26% of patients stated depressive symptoms (PHQ score ≥ 3). Table 1 shows the prevalence of depressive symptoms by disease entity which was not significantly different among the subgroups (χ2(5)=6, p=0.3). However, given our results indicating depressiveness to be common across subgroups, all of these patients merit further evaluation. The PHQ-2 was widely accepted by patients, and seemed very feasible due to its concise form. Conclusion The PHQ-2 questionnaire is a highly feasible and well accepted tool in routine clinical practice, helping to screen for depressive symptoms as a highly prevalent condition across rheumatic diseases. Real world evidence of depressive symptoms may improve healthcare by shedding light on the patients’ mental well-being and comorbidity. References [1] Brandstetter S, Riedelbeck G, Steinmann M, Loss J, Ehrenstein B, Apfelbacher C. Depression moderates the associations between beliefs about medicines and medication adherence in patients with rheumatoid arthritis: Cross-sectional study. J Health Psychol. 2016 May 04. [2] Kleinert S, Marx A, Faller H, M F, C K, Lehmann S, et al. Prevalence and Relevance of Depressive Symptoms in Patients with Rheumatic Diseases [abstract]. Arthritis Rheumatol 2015; 67 (suppl 10). 2015. [3] Lowe B, Kroenke K, Grafe K. Detecting and monitoring depression with a two-item questionnaire (PHQ-2). J Psychosom Res. 2005 Feb; 58(2):163-171. [4] Englbrecht M, Alten R, Aringer M, Baerwald CG, Burkhardt H, Eby N, et al. Validation of Standardized Questionnaires Evaluating Symptoms of Depression inRheumatoid Arthritis Patients: Approaches to Screening for a Frequent Yet Underrated Challenge. Arthritis Care Res (Hoboken). 2017 Jan; 69(1):58-66. Disclosure of Interests Stefan Kleinert Grant/research support from: Novartis, Consultant for: Novartis, UCB, Chugai, Celgene, Medac, Roche, Abbvie, Speakers bureau: Novartis, UCB, Chugai, Celgene, Medac, Roche, Abbvie, Florian Schuch Consultant for: Celgene, Lilly, UCB, Roche, Sanofi-Aventis, Abbvie, Novartis, Speakers bureau: Celgene, Lilly, UCB, Roche, Sanofi-Aventis, Abbvie, Praxedis Rapp: None declared, Monika Ronneberger Consultant for: Celgene, Novartis, Paid instructor for: Abbvie, Bristol Myers Squibb, Novartis, Speakers bureau: Celgene, Novartis, Bristol Myers Squibb, Pfizer, Joerg Wendler Consultant for: Roche Pharma AG, AbbVie, Jannssen Cilag, Novartis, Speakers bureau: Roche Pharma AG, AbbVie, Jannssen Cilag, Novartis, Matthias Englbrecht Grant/research support from: Roche Pharma AG, Chugai Pharma Europe Ltd., Consultant for: Roche Pharma AG, Chugai Pharma Europe Ltd., AbbVie Deutschland GmbH & Co. KG, Celgene GmbH, Lilly Deutschland GmbH, Speakers bureau: Roche Pharma AG, Chugai Pharma Europe Ltd., AbbVie Deutschland GmbH & Co. KG, Celgene GmbH, Lilly Deutschland GmbH

Background: Patient preferences (PP), which are investigated in PP studies using qualitative or quantitative methods, are a growing area of interest to the following stakeholders involved in the medical product lifecycle: academics, health technology assessment bodies, payers, industry, patients, physicians, and regulators. However, the use of PP in decisions along the medical product lifecycle remains limited. As the adoption of PP heavily relies on these stakeholders, knowledge of their perceptions of PP is critical. Objective: This study aimed to characterize stakeholders’ attitudes, needs, and concerns with respect to PP in decision making along the medical product lifecycle. Methods: Semi-structured interviews (n = 143) were conducted with academics (n = 24), health technology assessment/payer representatives (n = 24), industry representatives (n = 24), patients, caregivers and patient representatives (n = 24), physicians (n = 24), and regulators (n = 23) from seven European countries and the USA. Interviews were conducted between April and August 2017. The framework method was used to organize the data and identify themes and key findings in each interviewed stakeholder group. Results: Interviewees reported being unfamiliar (43%), moderately familiar (42%), or very familiar (15%) with preference methods and studies. Interviewees across stakeholder groups generally supported the idea of using PP in the medical product lifecycle but expressed mixed opinions about the feasibility and impact of using PP in decision making. Interviewees from all stakeholder groups stressed the importance of increasing stakeholders’ understanding of the concept of PP and preference methods and ensuring patients’ understanding of the questions asked in PP studies. Key concerns and needs in each interviewed stakeholder group were as follows: (1) academics: investigating the validity, reliability, reproducibility, and generalizability of preference methods; (2) health technology assessment/payer representatives: developing quality criteria for evaluating PP studies and gaining insights into how to weigh them in reimbursement/payer decision making; (3) industry representatives: obtaining guidance on PP studies and recognition on the importance of PP from decision makers; (4) patients, caregivers, and patient representatives: providing an incentive and adequate information towards patients when participating in PP studies; (5) physicians: avoiding bias as a result of commercial agendas in PP studies and clarifying how to deal with subjective and emotional elements when measuring PP; and (6) regulators: avoiding the misuse of PP study results to overrule the traditional efficacy and safety criteria used for marketing authorization and obtaining robust PP study results. Conclusions: Despite the interest all interviewed stakeholder groups reported in PP, the effective use of PP in decision making across the medical product lifecycle is currently hampered by a lack of standardization and consensus on how to both measure and use PP., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective To validate standard self-report questionnaires for depression screening in patients with rheumatoid arthritis (RA) and compare these measures to one another and to the Montgomery-Asberg Depression Rating Scale (MADRS), a standardized structured interview. Methods In 9 clinical centers across Germany, depressive symptomatology was assessed in 262 adult RA patients at baseline (T0) and at 12 ± 2 weeks followup (T1) using the World Health Organization 5-Item Well-Being Index (WHO-5), the Patient Health Questionnaire (PHQ-9), and the Beck Depression Inventory II (BDI-II). The construct validity of these depression questionnaires (using convergent and discriminant validity) was evaluated using Spearman's correlations at both time points. The test–retest reliability of the questionnaires was evaluated in RA patients who had not undergone a psychotherapeutic intervention or received antidepressants between T0 and T1. The sensitivity and the specificity of the questionnaires were calculated using the results of the MADRS, a structured interview, as the gold standard. Results According to Spearman's correlation coefficients, all questionnaires met convergent validity criteria (ρ > |0.50|), with the BDI-II performing best, while correlations with age and disease activity for all questionnaires met the criteria for discriminant validity (ρ 80%) when using the MADRS as the gold standard. Conclusion The BDI-II best met the predefined criteria, and the PHQ-9 met most of the validity criteria, with lower sensitivity and specificity.

The objective of this cross-sectional study was to define normal sex and age-dependent values of intra-articular bone mass and microstructures in the metacarpal heads of healthy individuals by high-resolution peripheral quantitative computed tomography (HR-pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra-articular bone. Healthy individuals of different sex and age categories and RA patients with similar age- and sex-distribution received HR-pQCT scans of the second metacarpal head and the radius. Total, cortical and trabecular bone densities as well as microstructural parameters were compared between (i) the different ages and sexes in healthy individuals, (ii) between metacarpal heads and the radius and (iii) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra-articular (=intra-capsular) bone margins. These data were applied in measuring intra-articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra-articular and radial bone parameters were good (r = 0.51 to 0.62, p

OBJECTIVE To search for evidence of secondary osteoarthritis (OA) in patients with rheumatoid arthritis (RA) in a cross-sectional and longitudinal setting, and to relate osteophyte formation to functional outcome. METHODS Anti-citrullinated protein antibody (ACPA)-positive RA patients underwent high-resolution peripheral quantitative computed tomography of the hand. Cross-sectional and longitudinal measurements were performed. The number and size (volume) of osteophytes as well as bone erosions were documented. The relationship of osteophytes to bone erosions and to demographic and disease-specific data was evaluated by multiple logistic regression models. RESULTS A total of 202 ACPA-positive RA patients were enrolled in the cross-sectional part of the study, and a total of 77 ACPA-positive RA patients were enrolled in the longitudinal analysis (interval of 1.5 years between baseline and follow-up assessment). The mean ± SD number of osteophytes per patient was 1.3 ± 2.3, and the mean ± SD osteophyte volume per patient was 2.6 ± 4.9 mm(3) . The total number of erosions was significantly correlated with the total number of osteophytes (P

Objectives To investigate the prevalence of monosodium urate (MSU) crystal deposits, indicative for gout, in a population of rheumatoid arthritis (RA) patients with concomitant hyperuricemia and to analyze the clinical and disease-specific characteristics of RA patients who exhibit MSU crystal deposits. Methods Overall, 100 consecutive patients with the diagnosis of RA and a serum urate level above 6mg/dl underwent dual energy computed tomography (DECT) of both feet and hands to search for MSU crystals in a prospective study between October 2011 and July 2013. Presence and extent of MSU crystal deposits on DECT was assessed by automated volume measurement. Demographic and disease-specific characteristics were recorded and included into two logistic regression models to test for the factors associated with MSU crystal deposits in RA. Results Hyperuricemic RA patients were mostly male (55%), over 60 years of age (63 ± 11 years), had established disease (8.7 ± 10.5 years) and a mean disease activity score 28 (DAS 28) of 3.2. In total, 20 out of 100 patients displayed MSU crystal deposits in DECT. Interestingly, the majority (70%) of the RA patients positive for MSU crystal deposits were seronegative RA patients. Hence, every third seronegative RA patient had MSU crystal deposits. According to logistic regression model analysis, seronegative status correlated positively with presence of urate deposits ( p = 0.019). Conclusions These data show that a considerable number of RA patients display periarticular MSU crystal deposits. Seronegative patients were shown to be predominantly affected with every third patient being positive for urate deposits.

Background:Deposition of uric acid crystals cause an inflammatory reaction, which can lead to structural bone changes, if such deposits form adjacent to cortical bone [1, 2]. Both erosions and bony spurs can form in conjunction with tophus deposition. The exact spatial inter-relation between tophi and structural bone lesions in humans in vivo is not fully characterized.Objectives:To spatially relate structural bone changes (erosions, osteophytes) to the deposition of monosodium urate crystals in the first metatarsophalangeal (MTP1) joint in patients with tophaceous gout.Methods:Tophaceous gout patients with clinically detected tophi at the MTP1 joint underwent simultaneous dual energy computed tomography (DECT) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the feet. Tophi detected by DECT and erosions and osteophytes detected by HR-pQCT were overlayed to define their exact anatomical relation. Furthermore, feet of sex- and age-matched healthy controls (HC) were scanned to define the normal architecture of the MTP1 joint.Results:Gout patients (N=20) had significantly higher numbers (5 (0–17 vs. 1 (1– 2)) and volumes (45.32 mm3(7.26–550.32) vs. 0.82 mm3(0.15–21.8)) of bone erosions as well as significantly higher numbers (10.5 (0-26) vs. 1 (0-10)) and sizes of osteophytes (4.93 mm (0.77-7.19 mm vs. 0.93 mm (0.05-7.61 mm))than healthy controls (N=20). Erosions were in direct spatial relation to bone erosions, while osteophytic responses were more widespread and affected bone regions on the MTP1, which were not directly adjacent to tophi. Median tophus volume detected by DECT (0.12 mm3(0.01–2.53)) was associated with the total volume of erosions (r=0.597, p=0.005).Conclusion:This study demonstrates that bone changes in gout are substantial and not only include erosions but also widespread architectural bone remodeling associated osteophyte formation. While there is a direct spatial relation between tophi and bone erosions the anabolic bone responses in gout are more widespread.References:[1]Dalbeth, N. et al. Ann Rheum Dis. 2015 Jun;74(6):1030-6.[2]Dalbeth, N. et al. Arthritis Res Ther. 2012; 14(4): R165.Data are based on high-resolution peripheral quantitative computed tomography (HR-pQCT) of metatarsophalangeal joints I in gout patients (grey boxplots) and healthy controls (white boxplots). (A) number of bone erosions, (B) volume of bone erosions, (C) number of osteophytes and (D) size of osteophytes. Data are shown as medians and inter-quartile ranges (boxes).Distribution of (A) tophi based on dual-energy computed tomography (DECT) as well as (B) bone erosions and (C) osteophytes based on high-resolution peripheral quantitative computed tomography (HR-pQCT) of metatarsophalangeal (MTP) I head in gout patients. Data are shown for the different regions of the MTPI head including the plantar, medial, dorsal and lateral region of the metatarsal head, as well as the medial and lateral sesamoid bones. Data indicate percentage of patients with tophi, erosions and osteophytes in respective region.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Caroline Pecherstorfer: None declared, Hanna Ellmann: None declared, Camille Figueiredo: None declared, Matthias Englbrecht: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:Symptom checkers (SC) promise to reduce diagnostic delay, misdiagnosis and effectively guide patients through healthcare systems. They are increasingly used, however little evidence exists about their real-life effectiveness.Objectives:The aim of this study was to evaluate the diagnostic accuracy, usage time, usability and perceived usefulness of two promising SC, ADA (www.ada.com) and Rheport (www.rheport.de). Furthermore, symptom duration and previous symptom checking was recorded.Methods:Cross-sectional interim clinical data from the first of three recruiting centers from the prospective, real-world, multicenter bETTeR-study (DKRS DRKS00017642) was used. Patients newly presenting to a secondary rheumatology outpatient clinic between September and December 2019 completed the ADA and Rheport SC. The time and answers were recorded and compared to the patient’s actual diagnosis. ADA provides up to 5 disease suggestions, Rheport calculates a risk score for rheumatic musculoskeletal diseases (RMDs) (≥1=RMD). For both SC the sensitivity, specificity was calculated regarding RMDs. Furthermore, patients completed a survey evaluating the SC usability using the system usability scale (SUS), perceived usefulness, previous symptom checking and symptom duration.Results:Of the 129 consecutive patients approached, 97 agreed to participate. 38% (37/97) of the presenting patients presented with an RMD (Figure 1). Mean symptom duration was 146 weeks and a mean number of 10 physician contacts occurred previously, to evaluate current symptoms. 56% (54/96) had previously checked their symptoms on the internet using search engines, spending a mean of 6 hours. Rheport showed a sensitivity of 49% (18/37) and specificity of 58% (35/60) concerning RMDs. ADA’s top 1 and top 5 disease suggestions concerning RMD showed a sensitivity of 43% (16/37) and 54% (20/37) and a specificity of 58% (35/60) and 52% (31/60), respectively. ADA listed the correct diagnosis of the patients with RMDs first or within the first 5 disease suggestions in 19% (7/37) and 30% (11/37), respectively. The average perceived usefulness for checking symptoms using ADA, internet search engines and Rheport was 3.0, 3.5 and 3.1 on a visual analog scale from 1-5 (5=very useful). 61% (59/96) and 64% (61/96) would recommend using ADA and Rheport, respectively. The mean SUS score of ADA and Rheport was 72/100 and 73/100. The mean usage time for ADA and Rheport was 8 and 9 minutes, respectively.Conclusion:This is the first prospective, real-world, multicenter study evaluating the diagnostic accuracy and other features of two currently used SC in rheumatology. These interim results suggest that diagnostic accuracy is limited, however SC are well accepted among patients and in some cases, correct diagnosis can be provided out of the pocket within few minutes, saving valuable time.Figure:Acknowledgments:This study was supported by an unrestricted research grant from Novartis.Disclosure of Interests:Johannes Knitza Grant/research support from: Research Grant: Novartis, Jacob Mohn: None declared, Christina Bergmann: None declared, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Melanie Hagen: None declared, Daniela Bohr: None declared, Elizabeth Araujo Speakers bureau: Novartis, Lilly, Abbott, Matthias Englbrecht Grant/research support from: Roche Pharma, Chugai Pharma Europe, Consultant of: AbbVie, Roche Pharma, RheumaDatenRhePort GbR, Speakers bureau: AbbVie, Celgene, Chugai Pharma Europe, Lilly, Mundipharma, Novartis, Pfizer, Roche Pharma, UCB, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Timo Meinderink: None declared, Wolfgang Vorbrüggen: None declared, Cay-Benedict von der Decken: None declared, Stefan Kleinert Shareholder of: Morphosys, Grant/research support from: Novartis, Consultant of: Novartis, Speakers bureau: Abbvie, Novartis, Celgene, Roche, Chugai, Janssen, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Peter Bartz-Bazzanella: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Martin Welcker Grant/research support from: Abbvie, Novartis, UCB, Hexal, BMS, Lilly, Roche, Celgene, Sanofi, Consultant of: Abbvie, Actelion, Aescu, Amgen, Celgene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Speakers bureau: Abbvie, Aescu, Amgen, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB

Objective: Little is known about the experiences, values and needs of people without arthritis who undergo predictive biomarker testing for the development of rheumatoid arthritis (RA). Our study aimed to explore the perspectives of these individuals and describe their information needs.\ud \ud Methods: A qualitative, multicenter interview study with a thematic analysis was conducted in Austria, Germany and the UK. Individuals who underwent predictive biomarker testing for RA and had a positive test result, but no diagnosis of any inflammatory joint disease, were interviewed. Participants included patients with arthralgia and asymptomatic individuals. Information and education needs were developed from the qualitative codes and themes using the Arthritis Educational Needs Assessment Tool (ENAT) as a frame of reference.\ud \ud Results: Thematic saturation was reached in 34 individuals (76% female; 24 [71%] with arthralgia and 10 [29%] asymptomatic individuals). Thirty‐seven codes were summarized into four themes, namely (i) decision making around whether to undergo initial predictive testing, (ii) willingness to consider further predictive tests and/or (iii) preventive interventions, including medication and (iv) varying reactions after receiving a positive test result. Individuals with arthralgia were more likely to be willing to take preventive action, undergo further testing, and experience psychological distress than asymptomatic individuals. All participants expressed the need for tailored, lay‐understandable information.\ud \ud Conclusion: Individuals at risk of RA are currently the subjects of research aimed at developing better predictive strategies and preventive approaches. Their perceptions and needs should be addressed to inform the future development of interventions combined with education.

Background Although the effects of interleukin-17A (IL-17A) inhibition on the signs and symptoms of psoriatic arthritis (PsA) are well defined, little is known about its impact of local inflammatory and structural changes in the joints. The PSARTROS study was designed to elucidate the effects of IL-17A inhibition on inflammation and bone changes in joints affected by PsA. Methods This was a prospective open-label study in 20 patients with active PsA receiving 24 weeks of treatment with the IL-17A inhibitor secukinumab. Magnetic resonance imaging (MRI), power Doppler ultrasound (PDUS), and high-resolution peripheral quantitative computer tomography (HR-pQCT) of the hands were performed at baseline and after 24 weeks to assess synovitis, periarticular inflammation, bone erosion, enthesiophyte formation, and bone structure. Demographic and clinical measures of joint disease (DAPSA and DAS28-ESR), skin disease (PASI and BSA), and composite measures (minimal disease activity, or MDA) were also recorded. Results Treatment with secukinumab led to significant improvement of signs and symptoms of PsA; 46% reached MDA and 52% DAPSA low disease activity. MRI synovitis (P = 0.034) and signal in PDUS (P = 0.030) significantly decreased after 24 weeks of treatment. Bone erosions in MRI and HR-pQCT and enthesiophytes in the HR-pQCT did not show any progression, and structural integrity and functional bone strength remained stable. Conclusions IL-17 inhibition by secukinumab over 24 weeks led to a significant decrease of synovial inflammation and no progression of catabolic and anabolic bone changes in the joints of patients with PsA. Trial registration ClinicalTrials.gov Identifier: NCT02483234, June 26, 2015; retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s13075-018-1653-5) contains supplementary material, which is available to authorized users.

Background: The non-interventional ARATA study (NCT02251860) observes the clinical effectiveness and safety of subcutaneous Tocilizumab [TCZ] s.c. treatment under routine conditions over a 2-year period. Objectives: In this interim analysis, the treatment with TCZ s.c., in particular with respect to patient-reported outcomes regarding depression, fatigue and pain, was evaluated. Methods: TCZ-naive patients (Pts) (≥18 years) with RA, who receive TCZ s.c. treatment, could be included in the study since 2014. Demographic and disease-specific characteristics, the progression of the disease under treatment, concomitant medications, adverse events (AE) and patient questionnaires were documented. Results: This interim analysis (reporting date 01-FEB-2017) included 912 Pts. 75% of the Pts were female, the average age at baseline (BL) was 57 years, the median disease duration was 8 years. 319 Pts (35%) were pretreated exclusively with sDMARD and 585 Pts (64%) were also pretreated with bDMARD. For the readjustment, TCZ s.c. was applied for 69% without sDMARD, 31% in combination with MTX and for 66% with glucocorticoids. In the course of the study, 65% of the Pts achieved a DAS28-BSG remission. Furthermore, the functional restrictions in day-to-day life (HAQ-DI D from BL: -0.3) improved. No new safety signals were observed. By means of the Beck Depression Inventory (BDI-II) score (Englbrecht et al., Arthritis Care Res 2017; 69:58–66), validated for RA, the depressive symptoms could be documented. At baseline, 186 Pts (50%) showed no, 70 (19%) minor, 67 (18%) moderate and 47 (13%) severe depression. Under the treatment with TCZ, the depressive symptoms improved (compare figure 1). The patients reported a significant improvement of the pain (VAS: average change from BL to week 52 by -21 points and to week 104 by -24 points) as well as the fatigue (VAS: average change from BL to week 52 by -11 points and 104 by -12 points). Conclusions: In the ARATA study, TCZ s.c. demonstrated an effective and persistent reduction in the disease activity of the treated RA patients. The patients confirmed improved physical functionality as well as less fatigue and pain. Depression plays an important role in RA, as the results of BDI-II highlight, whereby the depressive symptoms also improved distinctively under treatment with TCZ s.c. Disclosure of Interest: F. Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Novartis, Consultant for: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly, Boehringer, Sandoz, M. Englbrecht: None declared, W. A. Biewer: None declared, G.-R. Burmester Consultant for: Lilly, Pfizer, Sanofi, Roche, M. Feuchtenberger Consultant for: MSD, Roche, Abbvie, Chugai, Pfizer, UCB, J.-P. Flacke Employee of: Roche Pharma AG, M. Hofmann Employee of: Chugai Pharma Europe Ltd., P. Kastner: None declared, H. Kellner Consultant for: Roche, T. Klopsch: None declared, C. Kuhne Consultant for: Celgene, Roche, Pfizer, Novartis, BMS, H.-P. Tony Consultant for: Roche Pharma, Abbvie, BMS, Chugai, Janssen, Novartis, Sanofi, Lilly, Speakers bureau: Roche Pharma, Abbvie, BMS, Chugai, Janssen, Novartis, Sanofi, Lilly, C. Amberger Consultant for: Chugai, AbbVie, Celgene, MSD, Pfizer, BMS, HexaL

Background Functional properties of bone in rheumatoid arthritis (RA) are still not well characterised. Objectives This study aimed to define the impact of anti-citrullinated antibodies (ACPA) on biomechanical properties in RA. Methods Based on on high-resolution peripheral quantitative computed tomography (HR-pQCT) data from the distal radius of ACPA-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC) micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone.( 1 Comparisons of µFEA parameters between groups was calculated and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength. Results A total of 276 subjects (96 RA+, 84 RA- and 96 HC) were analysed. Age and sex distributions were not significantly different between the three groups. In RA +but not in RA- failure load and stiffness were significantly decreased compared to HC (both p Conclusions In summary, µFEA showed that bone strength is significantly decreased in RA +but not in RA- disease. Reference [1] Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone2008;42(6):1203–13. Disclosure of Interest None declared

Background Musculoskeletal changes precede the onset of psoriatic arthritis (PsA). A subset of psoriasis patients is characterised by arthralgia as well as inflammatory changes in the joints visible by MRI assessment. These patients have a high risk to progress into PsA. Objectives To test the concept of a very early intervention in PsA we exposed psoriasis patients with subclinical joint inflammation to the anti-interleukin (IL)−17A antibody secukinumab. We hypothesised that IL-17A inhibition disrupted the early link between skin and joint disease in psoriasis. Methods Psoriasis (but not PsA) patients were included in the open prospective 24 weeks ‘Interception in Very Early PSA’ (IVEPSA) study. To fulfil the inclusion criteria patients had to have a PASI score greater than 6 or nail or scalp involvement as well as inflammatory or erosive changes in MRI or high-resolution peripheral quantitative computed tomography (HRpQCT) at baseline. Patients received treatment with secukinumab 300 mg sc. for 24 weeks. MRI scans and HRpQCT of the dominant hand were performed at baseline and at 24 weeks. MRI was scored according to PsAMRIS. HRpQCT evaluated for erosions and enthesiophytes. Results 20 patients (median age 49.5 years (IQR 42.8, 59), 70% males) with a median disease duration of 14 years (IQR 5, 20), were included into the study. At baseline, 85% reported arthralgia assessed by a Visual Analogue Scale (VAS) and 40% had tender joints on examination (TJC78). 83.3% had at least one inflammatory lesion in the MRI, 66.7% synovitis, 55.6% tendinitis/enthesitis, 27.8% osteitis and 16.7% periarticular inflammation. Erosions were present in 72.2% and 58.8% in the MRI and HRpQCT, respectively, while enthesiophytes were found in 33.3% and 41.2%. One patient was discontinued early due to lack of improvement (wk12) and one patient was unable to perform the follow-up MRI. Psoriatic skin disease (total PASI and BSA) significantly improved (both p Conclusions IL-17 inhibition by secukinumab over 24 weeks led to resolution of inflammation and no progression of bone changes in the joints in psoriasis patients with subclinical peripheral joint involvement. These data suggest that very early disease interception in PsA is a feasible approach. IVEPSA also provides the guide for further very early interventions in PsA providing concepts for imaging-based identification and the sensitivity to change subclinical inflammation through biological disease modifying anti-rheumatic drug therapy. Acknowledgements This study was supported by an unrestricted grant from Novartis. Disclosure of Interest None declared

Background DAS28-ESR is the most widely used instrument to assess remission in rheumatoid arthritis (RA) patients. Nonetheless, substantial residual disease activity can be present in RA patients fullfilling DAS28-ESR remission. Therefore, more stringent criteria for remission have been developed. While it is known that patients can fulfil DAS28-ESR but fail ACR/EULAR Boolean remission criteria, the existence of the reverse is less known. Objectives To test the possibility to loose DAS28-ESR remission while staying in ACR/EULAR remission in patients with RA Methods Data were obtained from the prospective randomised RETRO study (EudraCT: 2009–015740–42), which recruits RA patients in stable remission. Remission was assessed by the following instruments every three months: DAS28-ESR, DAS28-CRP, CDAI, SDAI, PAS, and ACR/EULAR criteria. In the group of patients, escaping DAS28-ESR remission, but fulfilling ACR/EULAR Boolean remission, the individual components of DAS28-ESR were analysed that determined their escape from remission. Results 142 patients analysed, which were all in DAS28-ESR remission at baseline. Of them, 140 (98.59%) were in DAS-CRP-remission, 131 (92.25%) in CDAI-remission, 130 (91.55%) in SDAI-remission, 109 (76.76%) in ACR/EULAR remission and 66 (46.48%) in PAS-remission. We analysed upon the 1 year follow up those patients loosing DAS28-ESR remission over time: 58 patients lost DAS-ESR remission at least once during the 4 follow-up visits. Surprisingly, 24% (3 months), 36% (6 months), 24% (9 months) and 28% (12 months) of the patients still fulfilled the Boolean remission criteria. The only plausible reason for failing DAS28-ESR remission but staying in ACR/EULAR remission is an isolated elevation of the ESR, not accompanied by increased signs and symptoms of disease. Indeed all patients loosing DAS28-ESR remission but staying in ACR/EULAR Boolean remission had an elevated ESR equal or higher than 15 mm. However, if DAS28 scores were calculated by C-reactive protein in the same patients, they all fulfilled remission criteria. Conclusions DAS28-ESR remission can be missed even if a patient fulfils the more stringent ACR/EULAR Boolean remission criteria. The reason for this remarkable constellation is an elevated erythrocyte sedimentation rate without any clinical symptoms. Hence, isolated elevations of erythrocyte sedimentation rate should be seen critical. These data show the limitations of individual instruments to assess remission in RA and show that interpretations of the erythrocyte sedimentation rate need to be done in the clinical context Disclosure of Interest None declared

Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now allow the accurate measure of articular bone composition. In this study 476 subjects comprising healthy individuals and patients with anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA), ACPA-negative RA, Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO) and psoriatic arthritis (PsA) were subjected to high-resolution quantitative computed tomography (HR-pQCT) of the hand. Metacarpal heads were assessed for total, trabecular and cortical volumetric bone mineral density (vBMD). Only ACPA+RA, but not the remaining inflammatory diseases (ACPA-RA, CD, UC, PsO, PsA) showed significant (p 0.001) loss of articular bone affecting both the trabecular and the cortical compartments. Age and body mass index were also associated with articular bone changes, the former with lower, the latter with higher articular bone mass. In multivariate models, presence of ACPA+RA was an independent factor for articular bone loss. Among chronic inflammatory diseases ACPA+RA is the most potent precipitator for articular bone loss pointing out the role of autoimmunity in the development of articular bone disease in the context of chronic inflammatory disease.