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BackgroundThere is a growing research focus on the development of interventions to reduce risk of rheumatoid arthritis (RA) in at-risk individuals.(1) A recent survey of the general population asked to assume a 60% risk of RA established that hypothetical preventive treatments were acceptable to most participants.(2) However the preferences of individuals who actually have an elevated risk of RA, such as first-degree relatives (FDRs) of RA patients, are not well understood.ObjectivesTo quantify FDRs’ preferences for preventive treatments for RA.MethodsAdult FDRs in the UK and Germany were invited to take part in a web-based survey via patients with clinician-confirmed RA either during a rheumatology clinic visit or by mail. In addition, FDRs taking part in a UK-based prospective cohort (PREVeNT-RA) were invited via email. Participants received information about RA followed by questions to check comprehension, and an introduction to the survey including warm-up questions. They were asked to imagine they were experiencing arthralgia and had positive autoantibody tests indicating a 60% chance of developing RA in the next two years. Using a discrete choice experiment, participants were offered a series of 15 choices between no treatment and two unlabeled hypothetical treatments to reduce risk of RA. Treatments were defined by six attributes with varying levels, describing benefits, risks, and frequency/route of administration (Table 1). Attribute selection and presentation was informed by qualitative research, ranking surveys, systematic literature review, and expert opinion. Survey layout was informed by patient research partners and qualitative pre-testing. A two-class latent class analysis was used to estimate preferences and calculate relative importance of treatment attributes and predicted uptake. A panel mixed logit model was used to obtain maximum acceptable risk estimates.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 peopleResults356 FDRs (252 female, 289 in the UK) responded. While treatment effectiveness was the most important attribute in both classes (Figure 1), the importance of other attributes differed between classes, with method and frequency of treatment administration being more important in class 2 and risk of mild side effects only impacting treatment choice in class 1. Perceived risk of developing RA predicted class assignment; those with higher perceived risk were more likely to belong to class 1. On average, the predicted uptake of treatment profiles estimating prevention candidates: abatacept; atorvastatin; hydroxychloroquine; tolerogenic cell-based therapy; and no treatment would be 50%, 15%, 9%, 18% and 0%, respectively. Finally, the maximum acceptable risk participants were willing to accept were 81%, 25% and 3% point increases in risk of mild side effects, serious infection, and serious side effects, respectively, for medicines that would reduce their risk of developing RA in the upcoming two years from 60% to 20%.ConclusionEffective preventive treatments for RA were acceptable to FDRs asked to assume a 60% chance of developing RA. Mode and frequency of treatment administration had a greater impact on treatment choices for participants with a lower perceived risk of RA. These findings are informative for target product profile development, endpoint selection, benefit-risk assessment, regulatory approval, and development of informational resources for those at risk of RA.References[1]Mankia et al. Ann Rheum Dis. 2021;80(10):1286-98.[2]Simons et al. Ann Rheum Dis. 2021;80:96-7.AcknowledgementsOn 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). This abstract and its contents reflect the view of the presenter and not the view of PREFER, IMI, the European Union or EFPIA. K. Raza is supported by the NIHR Birmingham Biomedical Research Centre.Disclosure of InterestsGwenda Simons: None declared, Jorien Veldwijk: None declared, Rachael DiSantostefano Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, Matthias Englbrecht Speakers bureau: Abbvie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Munidpharma, 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, Jenny Humphreys: None declared, Ian N. Bruce: None declared, Karim Raza Consultant of: Abbvie, Sanofi, Grant/research support from: Bristol Myers Squibb, Marie Falahee: None declared

BackgroundRA is characterized by synovial inflammation resulting in local bone loss [1]. Inhibitors of JAK/Stat pathways, such as baricitinib, demonstrated efficacy in reducing signs and symptoms of RA in clinical trials, however, little is known about their effects on synovitis and bone structure [2]. Preclinical and clinical observations suggest a positive effect JAK inhibitors on bone mass and microstructure, however no prospective, interventional clinical trial has been performed so far [3].ObjectivesThe aim of this study is to evaluate the effect of baricitinib on local inflammation (synovitis and osteitis) and bone structure (erosions) in RA patients failing on cs/bDMARD therapy using hand MRI.MethodsBAREBONE is a prospective, interventional, open label, monocentric single center study (EUDRACT 2018-001164-32 / NCT03701789) to assess the effect of baricitinib (4mg/day) on local MRI inflammation and structure in patients with active RA. Besides demographic and clinical characteristics, hand joint inflammation was assessed by magnetic resonance imaging (MRI) using a 1.5 Tesla scanner (Siemens Magnetom Aera T1w TSE cor, T2w TIRM cor, T2w TSE fat-sat trans, T1w TSE fat-sat trans + cor after KM;). at baseline, week 24 and week 48. Scans were assessed for synovitis, osteitis and bone erosions using the RAMRIS scoring system using two independent blinded readers (SK and SB). Intraclass correlation coefficients were calculated for total RAMRIS and synovitis, erosion and osteitis subscores and in a second step differences between cs and bDMARD failure were elaborated. Variables are summarized descriptively using means and 95% bootstrap confidence intervals for continuous outcomes and as number and percentages for categorical outcomes.ResultsThirty- two RA patients were screened and 30 patients were included (age: 53.4 [SD 12.6] years; sex: f/m N 24/6; disease duration: 3 [IQR 2.0 – 8.0] years; biologic naïve/bDMARD failure 16/14). 27 patients completed the trial while MRI data was available for 24 patients at week 48. Demographics and clinical characteristics can be seen in Table 1. Total RAMRIS scores slightly decreased from 20.6 (95% CI 14.4 -27.8) at baseline (BL) to 18.3 (11.5 -26.5) at week 48. The synovitis subscore mainly contributed to total RAMRIS reduction by significantly improving from 5.3 (4.0 - 6.8) at BL to 2.7 (1.5 - 4.0) at week 48 with a score change of -2.9 (-4.0 to -1.8). At week 48, 12 patients (44.4%) had no signs of synovitis compared to only 3 patients at BL. In contrast, RAMRIS osteitis subscores only marginally decreased from 4.9 (2.2 - 8.4) at BL to 4.0 (1.9 - 6.7) at week 48. RAMRIS erosion score remained stable over the 48-week observation time. A significant difference in RAMRIS synovitis change for biologic naïve -3.8 (-5.2 to -2.6) vs biologic failure -1.0 (-2.2 to 0.4 could be observed at week 48).With respect to clinical disease activity, DAS 28 score decreased from 4.8 (4.5 – 5.1) at BL to 2.9 (2.5 – 3.3) at week 48. Detailed results can be found in Table 1 and Figure 1. Intraclass coefficient (95%CI) for RAMRIS scoring was high for both readers 0.997 (0.994 to 0.998).Table 1.Demographics, DAS 28 ESR, RAMRIS total score and RAMRIS subset scores at baseline, week 24 and week 48 are shown as well as number of patients with improvement and resolution of synovitis.BaselineWeek 24Week 48N303027AgeMean [SD]53.5 (12.6)Genderfemalen [%]24 (80.0)malen [%]6 (20.0)Disease duration, yearsMedian (IQR)3.0 (2.0-8.0)DAS-28 ESRMean [95%CI]4.8 (4.5 to 5.1)3.0 (2.7 to 3.3)2.7 (2.4 to 3.0)MRI availablen [%]30 (100.0)28 (93.3)24 (88.9)RAMRIS totalMean [95%CI]20.6 (14.4 to 27.6)18.4 (12.6 to 25.4)18.3 (11.5 to 26.5)RAMRIS total changeMean [95%CI]0.0 (0.0 to 0.0)-2.1 (-4.0 to -0.4)-3.9 (-7.2 to -0.5)RAMRIS synovitisMean [95%CI]5.3 (3.9 to 6.9)3.5 (2.2 to 4.9)2.7 (1.5 to 4.0)RAMRIS synovitis changeMean [95%CI]0.0 (0.0 to 0.0)-1.8 (-2.5 to -1.0)-2.9 (-4.0 to -1.8)RAMRIS synovitis improvedpatients n [%]10 (33.3)13 (48.1)RAMRIS synovitis resolvedpatients n [%]10 (33.3)12 (44.4)RAMRIS osteitisMean [95%CI]4.9 (2.2 to 8.4)3.7 (1.5 to 6.2)4.0 (1.9 to 6.7)RAMRIS osteitis changeMean [95%CI]0.0 (0.0 to 0.0)-0.9 (-3.1 to 1.0)-1.9 (-5.7 to 1.1)RAMRIS osteitis improvedpatients n [%]2 (6.7)4 (14.8)RAMRIS erosionMean [95%CI]10.4 (7.3 to 14.6)11.2 (7.7 to 15.0)11.6 (7.5 to 16.6)RAMRIS erosion changeMean [95%CI]0.0 (0.0 to 0.0)0.6 (0.1 to 1.2)0.9 (0.0 to 2.1)RAMRIS erosion worsenedpatients n [%]2 (6.7)3 (11.1)ConclusionOur study shows that baricitinib primarily reduces MRI synovitis in RA patients that have previously failed csDMARD and bDMARD therapy and particularly in patients who are biologic naïve.References[1]McInnes, I.B. and G. Schett, The pathogenesis of rheumatoid arthritis. N Engl J Med, 2011.[2]Genovese, M.C., et al., Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med, 2016[3]Adam, S., et al., JAK inhibition increases bone mass in steady-state conditions and ameliorates pathological bone loss by stimulating osteoblast function. Sci Transl Med, 2020.AcknowledgementsLilly Deutschland GmbH funded the Barebone trialDisclosure of InterestsStephan Kemenes: None declared, Sara Bayat: None declared, David Simon Speakers bureau: Lilly Pharma Deutschland GmbH, Janssen, Consultant of: BMS, Pfizer, Sanofi, Abbvie, Janssen, Medac, Novartis,Lilly Deutschland GmbH, GileaBMS, Pfizer, Sanofi, Abbvie, Janssen, Medac, Novartis,Lilly Deutschland GmbH, Gilead, Amgend,, Grant/research support from: Novartis, Gilead, Abbvie, Lilly, Gerhard Krönke Speakers bureau: GSK, Novartis, Consultant of: GSK, Lilly, Novartis, Janssen, Grant/research support from: Lilly, Novartis, BMS, Janssen, Daniela Bohr: None declared, Larissa Valor: None declared, Fabian Hartmann: None declared, Louis Schuster: None declared, Koray Tascilar Speakers bureau: Gilead speaker, Consultant of: UCB, Lilly, Georg Schett Speakers bureau: Janssen, Abbvie, BMS, Lilly, Novartis, Roche, AMGEN, Gilead, UCB, Consultant of: Lilly, Novartis, Abbvie, Grant/research support from: Chugai, Lilly, Novartis, Arnd Kleyer Speakers bureau: Lilly, Novartis, Abbvie, Consultant of: BMS, Pfizer, Sanofi, Abbvie, Janssen, Medac, Novartis,Lilly Deutschland GmbH, Gilead, Amgen, Grant/research support from: Novartis, Lilly Deutschland GmbH, Gilead

The aims of this study were to describe the long-term retention rate of golimumab (GLM) treatment in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA) in real life, and to analyze determinants of discontinuation. METHODS We conducted a single-center, medical records review of all patients with RA, PsA, and SpA on GLM treatment attending a large rheumatology department from 2010 to 2017. Times from start to end of GLM treatment were collected, as well as sociodemographic, clinical, and safety variables. Golimumab retention rate was estimated by the Kaplan-Meier method, and comparison across diseases was analyzed with the Mantel-Haenszel statistic (log-rank test). Cox proportional hazards regression models were used to identify factors associated with GLM discontinuation. RESULTS In the study period, a total of 212 patients (61 RA, 48 PsA, 103 SpA) were prescribed GLM. Retention rates were 72% in the first year, 61% in the second, 56% in the third, and 38% at 5 years. Differences were statistically significant across diseases (median times to GLM discontinuation were 50.2, 46.0, and 38.7 months for RA, SpA, and PsA, respectively) and according to the number of previous biologic therapies (55.2 months in biologic-naive patients vs 14.0 months in patients with ≥2 previous biologics; p < 0.001). The use of concomitant conventional synthetic disease-modifying antirheumatic drugs was associated with a lower probability of discontinuation (hazards ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.97). Female sex (HR, 1.84; 95% CI, 1.07-3.17) and having used 2 biologics before GLM (HR, 2.99; 95% CI, 1.76-5.06) were associated with increased discontinuation rates. Twenty-three patients (10.9%) had at least 1 serious adverse event. CONCLUSIONS In a real-life setting, GLM shows appropriate long-term safety-effectiveness ratio.

BackgroundThe development of RA is described by a preclinical phase of autoimmunity, that precedes clinical disease. This autoimmune phase is characterized by the presence of anti-modified protein antibodies that recognize citrullinated proteins (ACPA). A subset of individuals with ACPA develops RA, i.e. those with imaging signs of subclinical inflammation in the joints. As T cell mediated B cell activation is a key step in developing autoimmunity and RA, interventions that target this process may be useful for preventing the onset of RA. In this context, abatacept seems being an attractive therapeutic tool as it interrupts the activation of T cells and has a favourable safety profile in the treatment of RA.ObjectivesTo test whether treatment of abatacept, as compared to placebo, delays the onset of RA in ACPA positive individuals with a high risk to develop RA.MethodsARIAA is an international, randomized double-blinded placebo-controlled multi-center study in RA-at risk individuals, being ACPA positive and showing MRI signs of inflammation. The study was composed of a 6 months treatment phase with either abatacept s.c. 125 mg weekly or placebo and a 12 months observation phase with no treatment. Primary endpoint was the improvement of MRI inflammation after 6 months, secondary endpoints were the progression to RA after 6 and 18 months. The primary analysis was done on the ITT population and missing values were classified as treatment failures.ResultsBetween November 2014 and December 2019 139 RA-at risk individuals were included into ARIAA by 14 study sites (11 in Germany, 1 in the Czech Republic and 2 in Spain). Of them, 100 patients were randomized to receive either abatacept or placebo. Two patients were excluded and 98 patients could be evaluated for efficacy and safety. The primary endpoint was met: 61% of abatacept and 31% of placebo treated individuals (p=0.0043) improved in MRI inflammation. Furthermore, only 4 patients (8.2%) in the abatacept group but 17 patients in the placebo group (34.7%) progressed to RA after 6 months (p= 0.0025). Even 1 year after cessation of treatment (18 months after inclusion) the number of patients progressing to RA was lower in the abatacept group (35%) than in the placebo group (57%; p=0.0421). With respect to safety, 12 serious adverse events (each one gastritis, cellulitis, pneumonia, tendinitis calcificans, rotator cuff syndrome, cholelithiasis, peripheral artery disease, idiopathic pain syndrome, prostate cancer, penile neoplasm; trabeculectomy, cataract surgery) were reported, with only one (pneumonia) being considered to be related to treatment.ConclusionAbatacept significantly reduces subclinical joint inflammation and delays the development of RA in at-risk individuals.Table 1.ABAPBOAllN494998Females, N (%)31 (63.3)39 (79.6)70 (71.4)Age (ys); mean (±SD)51.3 (±10.8)48.5 (±12.6)49.9 (±11.7)SJC (N); mean (±SD)000TJC (N); mean (±SD)3.06 (± 3.75)3.51 (± 4.42)3.29 (±4.08)VAS Pain (mm) mean (±SD)42.2 (± 27.1)42.8 (± 33.2)42.5 (± 30.2)VAS PG (mm) mean (±SD42.2 (±28.7)43.0 (± 33.8)42.6 (± 31.2)MRI improvement, N (%)30 (61.2)15 (30.6)45 (45.9)RA at 6 months, N (%)4 (8.2)17 (34.7)21 (21.4)RA at 18 months, N (%)17 (34.7)28 (57.1)45 (45.9)AcknowledgementsThe study was supported by BMS according to the items outlined in the IIS contract and the IMI funded project RTCure.Disclosure of InterestsJürgen Rech Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultancy: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Sobi, Novartis, Arnd Kleyer Consultant of: BMS, Pfizer, Sanofi, Abbvie, Janssen, Medac, Novartis, Lilly Deutschland GmbH, Gilead, Amgen, Grant/research support from: Novartis, Lilly Deutschland GmbH, Mikkel Østergaard: None declared, Melanie Hagen: None declared, Larissa Valor: None declared, Koray Tascilar: None declared, Gerhard Krönke: None declared, Verena Schönau: None declared, Stefan Kleinert: None declared, Xenofon Baraliakos: None declared, Juergen Braun: None declared, Martin Fleck: None declared, Andrea Rubbert-Roth: None declared, Frank Behrens: None declared, Martin Feuchtenberger: None declared, Michael Zaenker: None declared, David M Kofler: None declared, Reinhard Voll: None declared, Cornelia Glaser: None declared, Axel Hueber: None declared, Eugen Feist: None declared, Gerd Rüdiger Burmester: None declared, Kirsten Karberg: None declared, Johannes Strunk: None declared, Juan de Dios Cañete: None declared, Ladislav Šenolt: None declared, Esperanza Naredo: None declared, Georg Schett: None declared.

BackgroundThere is a growing research focus on the development of interventions to reduce risk of rheumatoid arthritis (RA) in at-risk groups.(1) RA patients’ first-degree relatives (FDRs) have an elevated risk of developing RA and are potential candidates for preventive interventions. Recent studies have quantified the preferences of at risk groups for preventive treatments.(2-4) Little is known about predictors of preference heterogeneity in this context.ObjectivesAssess the extent to which FDR characteristics and beliefs predict risk tolerances for preventive treatments.MethodsAdult FDRs of patients with confirmed RA in the UK were invited to take part in a web-based survey. FDRs enrolled in a UK prospective cohort (PREVeNT-RA) were also invited. Survey development, including attribute selection and presentation, was informed by qualitative research, ranking surveys, literature review, and expert opinion including patient research partners. Respondents received information about RA, questions to check comprehension, and an introduction to the survey. Participants were asked to imagine they were experiencing arthralgia and had positive autoantibody tests indicating a 60% chance of developing RA within two years. Using a probabilistic threshold technique, participants made choices between no treatment (no benefit and no risks) or a preventive treatment option. Treatment options were defined by a fixed level of benefit (reduction in risk of RA from 60% to 20%) and varying levels of risks (Table 1). For each treatment risk, participants made a series of choices where the risk was systematically increased or decreased until they switched their choice. This procedure was repeated for each of the remaining risks. Participants also completed items assessing demographics, perceived risk of developing RA, health literacy, subjective numeracy, the Brief Illness Perception Questionnaire (IPQ) and the Beliefs about Medicines Questionnaire General (BMQ-G). The maximum acceptable risk (MAR) respondents were willing to accept for a 40% (60% to 20%) point risk reduction in developing RA was summarized across participants using descriptive statistics. Associations between MARs and participants’ characteristics and illness/medication beliefs were assessed using interval regression. Independent variables were dichotomized and effects coded.Table 1.Attributes and levels of treatment optionsTreatment attributeLevels describing no treatment optionLevels describing treatment optionChance of developing RA60%20%Chance of mild side effects0%2%; 4%; 5%; 7% or 10%Chance of a serious infection due to treatment0%1%; 1.5%; 2%; 3% or 5%Chance of a serious side effect that is potentially irreversible0%0.001%; 0.01%; 0.02%; 0.05% or 0.1%Results289 FDRs (80 male) responded. The mean (SE) MAR for mild side effects, serious infection, and serious side effects was 29.08 (1.52), 9.09 (0.60) and 0.85 (0.27), respectively. Participants aged over 60 years were less tolerant of risk of serious infection than average (mean MAR - 2.06 (0.78)) and younger participants were more tolerant of risk of serious infection than average (mean MAR + 2.06 (0.78)). Risk of mild side effects was less acceptable to participants who perceived they were likely/very likely to develop RA (mean MAR - 3.34 (1.55)) than to those who did not (mean MAR + 3.34 (1.55)). Education level, health literacy, numeracy, IPQ and BMQ-G subscales were not predictors of risk tolerance.ConclusionAge and perceived risk of RA had a significant impact on FDRs’ tolerance for specific, but not all, included risks. Cognitive ability and beliefs about RA/medicine did not explain preference heterogeneity. This is informative for drug development and the development of tailored risk communication resources to support preventive approaches.References[1]Mankia et al. Ann Rheum Dis. 2021;80(10):1286-98.[2]Simons et al. Ann Rheum Dis. 2021;80:96-7.[3]Harrison et al. Plos One. 2009; 14(4): e0216075.[4]Finckh et al. Curr Rheumatol Rep. 2016;18: 51.AcknowledgementsOn 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 InterestsGwenda Simons: None declared, Ellen Janssen Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, Jorien Veldwijk: None declared, Rachael DiSantostefano Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, 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, Employee of: Eli Lilly, Larissa Valor: None declared, Jenny Humphreys: None declared, Ian N. Bruce: None declared, Brett Hauber Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., Karim Raza Consultant of: Abbvie, Sanofi, Grant/research support from: Bristol Myers Squibb, Marie Falahee: None declared.

BackgroundTreatment success of a rheumatic disease crucially depends on whether a patient is sufficiently informed about the disease[1]. Visual methods are suitable for explaining diseases[2]. Cinematic rendering (CR) is a new method that allows to segment standard medical images into images that illustrate disease pathologies in a photorealistic way. As such, CR provides new opportunities to visualize diseases and but could therefore be a valuable tool for patients with rheumatic and musculoskeletal disease (RMD).[3]ObjectivesWe questioned, if it is possible to apply CR on images from structural lesions of patients with rheumatoid arthritis (RA), Psoriatic Arthritis (PsA) and axial Spondyloarthritis (axSpA) and to test whether such images are helpful to patients with RMDs to understand their disease process. application in doctor-patient communication.MethodsWe selected conventional computed tomography (CT) and high-resolution peripheral CT (HR-pQCT) from patients with rheumatoid arthritis (RA), Psoriatic Arthritis (PsA) and axial Spondyloarthritis (axSpA) that showed typical changes of the respective disease. HR-pQCT measurements were performed in RA and PsA at the Rheumatology Department. CT Measurements of the spine in an axSpA patient was provided from AH. All images were segmented to CR images using a prototype software by the manufacturer Siemens Healthineers. In a prospective study on consecutive patients with RA, PsA, axSpA these images were used to explain the depicted pathognomonic pathologies and compared to conventional imaging in a structured doctor-patient interview. In the last step, patients filled in a quantitative questionnaire (Likert Scale 1-5) about their perspectives answering following questions: Did you understand your disease in the provided Cinematic Rendering images? Did you understand your disease better through the presentation using Cinematic Rendering images than with a normal X-ray image? Do you think it would be reasonable to use this type of Cinematic Rendering to improve patients’ understanding of their disease? Descriptive statistical methods were used.ResultsCR images of rheumatic diseases were successfully generated from above mentioned imaging data (CT, HR-pQCT). Bone erosions, osteophytes, enthesiophytes, osteoporosis and ankylosis of the spine could be visualized in photorealistic detail. Figure 1 shows examples of a images of a patient with RA and axSpA with typical bone changes.65 patients (23 RA/23 PsA/19 axSpA; f 55%) were guided through CR images of their respective disease by an experienced rheumatologist, followed by completing the questionnaire mentioned above. Patients stated that CR was very helpful to understand their disease process (4.39±0.15), that understanding diseases by CR was better than the one obtained by conventional radiographs (4.43±0.20) and that they considered such technology helpful for improving disease understanding (4.35±0.09).ConclusionCR seems to be a promising teaching tool for RMD patients facilitating an improved understanding of their disease process and in consequence my also improve adherence of RMD patients to their anti-rheumatic treatment.References[1]Ritschl, V., et al., 2020 EULAR points to consider for the prevention, screening, assessment and management of non-adherence to treatment in people with rheumatic and musculoskeletal diseases for use in clinical practice. Ann Rheum Dis, 2020.[2]Kleyer, A., et al., Development of three-dimensional prints of arthritic joints for supporting patients’ awareness to structural damage. Arthritis Res Ther, 2017. 19(1): p. 34.[3]Berger, F., et al., Application of Cinematic Rendering in Clinical Routine CT Examination of Ankle Sprains. AJR Am J Roentgenol, 2018. 211(4): p. 887-890.AcknowledgementsSiemens Healthineers /Dr.Klaus Engel for providing CR expertiseDisclosure of InterestsNone declared

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:Due to better treatment strategies and higher remission rates the management of rheumatoid arthritis (RA) patients in sustained remission is of increasing interest (1). The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated the possibility to taper and stop disease modifying anti-rheumatic drugs (DMARDs).Objectives:To compare one-year remission and relapse rates in rheumatoid arthritis patients randomized to continued treatment, reduced treatment or gradual treatment withdrawal after stable remission under routine care.Methods:Primary data of the phase III, randomized, controlled RETRO trial in RA patients with stable conventional synthetic and/or biologic DMARD treatment in sustained (>6 months) DAS28-ESR remission (Results:316 RA patients in sustained remission were included, 303 were randomized (CONT: N=100; TAP: N=102; STOP: N=101) and 282 (93%) had complete data sets after 1 year (CONT:N=93; TAP: N=93; STOP: N=96; Table 1). After 1 year, 81.2%, 58.6%, 43.3% of patients, maintained their remission state over 1 year in the CONT, TAP and STOP arms, respectively (p=0.0004 with log rank test for trend; Figure 1). Hazard ratios for flare were 3.02 (95%CI 1.69 to 5.40) and 4.34 (95%CI 2.48 to 7.60) for the TAP and STOP arms. RA patients who flared were more likely to be female, have longer disease duration, RF/ACPA positivity and higher baseline DAS-28 scores with standardized mean differences >0.2. Serious adverse events were reported in 10.8%, 7.5%, and 13.5% in the CONT, TAP and STOP arms, respectively.Table 1.Baseline CharacteristicsGroupControlReduceReduce/StopOverallN939396282Age, mean(SD)55.9 (12.7)56.9 (13.0)56.5 (13.3)56.5 (13.0)Female, n (%)53 (57.0)57 (62.0)57 (59.4)167 (59.4)RF, n (%)52 (55.9)58 (62.4)52 (54.2)162 (57.4)ACPA, n (%)53 (57.0)50 (54.9)55 (57.3)158 (56.4)Disease duration, years, mean(SD)7.6 (6.9)7.8 (6.9)6.8 (8.1)7.4 (7.3)Remission duration, months, mean(SD)20.6 (18.0)16.5 (15.9)22.7 (30.4)20.0 (22.6)Biologics, n (%)39 (41.9)44 (47.3)39 (40.6)122 (43.3)Methotrexate, n (%)71 (76.3)67 (72.0)75 (78.1)213 (75.5)Other DMARDs, n (%)24 (25.8)20 (21.5)16 (16.7)60 (21.3)Glucocorticoids, n (%)27 (29.0)23 (24.7)17 (17.7)67 (23.8)CRP, mg/L, mean(SD)0.3 (0.3)0.5 (0.5)0.5 (0.6)0.4 (0.5)ESR, mm/h, mean(SD)11.3 (8.4)12.2 (8.8)13.0 (10.0)12.2 (9.1)Tender joint count, mean(SD)0.2 (0.6)0.0 (0.2)0.1 (0.3)0.1 (0.4)Swollen joint count, mean(SD)0.1 (0.3)0.1 (0.3)0.1 (0.4)0.1 (0.3)Physician VAS,mm, mean(SD)1.8 (4.2)2.6 (4.4)2.0 (3.9)2.1 (4.2)Patient VAS,mm, mean(SD)6.4 (9.0)5.5 (8.3)4.5 (8.4)5.5 (8.6)HAQ, standard, mean(SD)0.2 (0.4)0.2 (0.3)0.2 (0.4)0.2 (0.4)HAQ, alternative, mean(SD)0.2 (0.4)0.1 (0.3)0.2 (0.3)0.2 (0.3)DAS-28, mean(SD)1.7 (0.7)1.7 (0.6)1.7 (0.6)1.7 (0.6)SDAI, mean(SD)1.4 (1.5)1.4 (1.5)1.3 (1.3)1.3 (1.4)DAS-28 remission, n (%)91 (97.8)93 (100.0)95 (99.0)279 (98.9)SDAI remission, n (%)79 (87.8)79 (84.9)88 (92.6)246 (88.5)Boolean remission, n (%)69 (75.8)71 (76.3)76 (79.2)216 (77.1)Conclusion:This randomized controlled study shows that half of RA patients in sustained remission relapse when tapering/stopping their DMARDs. Presence of autoantibodies, higher baseline DAS28-ESR and female sex are predictors for flares.References:[1]Schett G et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016 Aug;75(8):1428-37.Disclosure of Interests:Melanie Hagen Speakers bureau: advisory boards, Koray Tascilar Speakers bureau: advisory board, Michaela Reiser: None declared, Larissa Valor: None declared, Judith Haschka Speakers bureau: advisory board, Arnd Kleyer Speakers bureau: advisory board, Axel Hueber Speakers bureau: advisory boards, Bernhard Manger Speakers bureau: advisory boards, Jayme Cobra Speakers bureau: advisory boards, Camille Figuereido Speakers bureau: advisory boards, Stephanie Finzel Speakers bureau: advisory boards, Hans-Peter Tony Speakers bureau: advisory boards, Joerg Wendler Speakers bureau: advisory boards, Stefan Kleinert Speakers bureau: advisory boards, Florian Schuch Speakers bureau: advisory boards, Monika Ronneberger: None declared, Martin Feuchtenberger Speakers bureau: advisory boards, Martin Fleck Speakers bureau: advisory boards, Karin Manger: None declared, Wolfgang Ochs: None declared, Matthias Schmitt-Haendle: None declared, Hanns-Martin Lorenz Speakers bureau: advisory boards, Rieke Alten Speakers bureau: advisory boards, Jörg Henes Speakers bureau: advisory boards, Klaus Krueger Speakers bureau: advisory boards, Jürgen Rech Speakers bureau: advisory boards, Georg Schett Speakers bureau: advisory boards.

Background:We have previously observed in RA patients that central nervous system (CNS) response to compression of a painful joint, measured using functional MRI (fMRI) of the brain as the number of blood oxygen level dependent (BOLD) signal positive voxels, is rapidly ameliorated, much earlier than any clinical response with anti-TNF treatment and a high baseline CNS pain response could predict better response to certolizumab pegol (CZP) treatment. Pre-CePRA was designed and conducted to test this effect in a randomized, placebo controlled trial of CZP and showed an incremental linear trend of DAS28 low disease activity (LDA) across study groups treated with placebo, and two CZP arms stratified as low or high pre-treatment CNS pain response.Objectives:To explore and describe pre-treatment CNS pain response associations with post treatment course of RA disease activity components and patient-physician discrepancy in global disease assessment.Methods:Patients fulfilling the 2010 ACR/EULAR classification criteria with moderate-severe disease activity (DAS-28>3.2) under stable DMARD treatment were recruited. Patients underwent an fMRI scan, stratified by a whole-brain BOLD positive voxel count threshold of 700 units and randomized to treatment with CZP or placebo in a 2:1 ratio. We descriptively assessed components of RA disease activity (Table 1 + 2). We summarized the mean results and 95% confidence intervals of these measurements at study timepoints and compared the 3 study groups at week 12 using one-way ANOVA and post-hoc Tukey tests.Results:156 eligible patients were screened and 139 (99 females, 71%) patients with moderate-high disease activity were randomized. ANOVA and pairwise comparisons showed that PGA-VAS improvement was larger in the CZP-H group whereas more similar to that in placebo in the CZP-L group. PhysGA-VAS however was similarly reduced in both CZP groups. Patients in the CZP-L group constantly rated their pain numerically higher than physicians whereas in the CZP-H group an initially higher discrepancy numerically reduced over time.Conclusion:These results suggest that improved patient global disease activity assessment could be the main driver of improved DAS-28 LDA rates with CZP treatment in patients with a high CNS pain response. Our findings indicate a potential role of fMRI imaging of the brain to further understand disease activity perception in RA patients.Figure 1.Course of disease activity components through trial timepoints. *indicates log-transformed y axis. *#x002A; Discrepancy equals Patient global minus physician global assessment.Disclosure of Interests:Hannah Schenker: None declared, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Melanie Hagen: None declared, Verena Schönau: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Larissa Valor: 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, 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, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:Tumor necrosis factor inhibitors have revolutionized the treatment of rheumatoid arthritis (RA). However, only about 50% of the patients respond well to TNF inhibitors. Therefore, markers that predict response to TNF inhibitors are valuable. Previously we demonstrated that central nervous system (CNS) response to nociceptive stimuli, measured by fMRI of the brain as blood oxygen level dependent (BOLD) signals, decreases already after 24 hours of anti-TNF administration a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumabpegol (CZP)1,2. We therefore hypothesized that the baseline volume of BOLD signal in the CNS could predict anti-TNF treatment response.Objectives:To perform a randomized placebo controlled trial in active RA patients to test the effect of TNF inhibition on arthritis induced pain activity in the brain and to test whether patients with high-level RA-related brain activation react differently to TNF-inhibitors than patients with low-level brain activation.Methods:Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28>3.2 receiving stable DMARD treatment for at least 3 months were eligible. Patients underwent the first fMRI at screening measuring BOLD signal upon MCP joint compression and were stratified into low (< 700 units) and high (>700 units) voxel counts. Then patients were randomized to CZP or placebo with a 2:1 ratio. The second and third fMRI were performed after 12 and 24 weeks, respectively. Control stimulation was done by measuring brain activation after non-painful finger tapping.Results:156 RA patients with moderate-to-high disease activity participated in the study. In the finger tapping control, fMRI showed no significant changes in BOLD signal in the CZP-L and CZP-H arms, but a slight but significant decrease (p=0.043) was observed. After joint compression, the CZP-L group showed significant increase in the BOLD signal volume (p=0.043) in fMRI-2 as compared to fMRI-1 with no further significant changes. In contrast, in the CZP-H group, the BOLD signal volume significantly decreased (p=0.037) in fMRI-2 and continued to decrease further, p=0.007. No significant changes were observed in the placebo arm over time.Conclusion:TNF inhibition improves arthritis-related brain activity in the subgroup of RA patients with high baseline BOLD activity in the fMRI.References:[1]Hess, A.et al.PNAS (2011).[2]Rech, J. et al. Arthritis & Rheumatism (2013).Fig 1.BOLD fMRI responses to painful stimulationAcknowledgments:The study was supported by an unrestricted grant of UCB Biopharma SPRL Brussels, BelgiumDisclosure of Interests:Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Hannah Schenker: None declared, Melanie Hagen: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Verena Schönau: None declared, Larissa Valor: 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, 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, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT-ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO-RA), patients who showed no response to first- and second-line treatments (NR-ITP), and healthy controls. Platelets from NR-ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR-ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T-regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR-ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.

Background: Persistent drug-free remission of RA is a condition that is close to “cure” of the disease. However, long-term drug-free remission is considered to be rare and very challenging to reach. Also, little data are available that report how often persistent drug-free remission can be achieved and what kind of clinical characteristics are associated with such state. Objectives: To evaluate factors associated with persistent drug-free remission in patients with rheumatoid arthritis Methods: We analyzed the long-term observational follow-up phase of the randomized controlled RETRO (REduction of Therapy in RA Patients in Ongoing Remission) study on tapering and stopping of DMARDS in RA patients in stable remission (DAS28-ESR Results: All 141 patients being in the long-term observational follow-up phase of the RETRO study for at least 1 year were analyzed. Among them DMARDs were initially continued (Control, n=38), tapered (Taper, n=50) or stopped (Taper/Stop n=53). 19/141 patients were lost to follow-up and the worst case scenario was assumed that all of them did not reach persistent drug-free remission. Median time after study entry (Q1-Q3) was 69 (37-96) months as by December 2018. Overall number of patients in drug-free remission was 34/141 (24.1%), 10/38 (26%) in the control group, 6/50 (12%) in the taper group and 18/53 (34%) in the taper/stop group. After adjustment for baseline risk factors in the likelihood to reach persistent drug-free remission between the groups (OR:0.76, 95%CI: 0.29-1.99) was highly uncertain. Positive ACPA (OR: 3.38, 1.01 – 11.31) and erosive-state (3.05, 1.32 – 7.06) at baseline were associated with a lower likelihood to reach persistent drug-free remission. Conclusion: These data show that persistent drug-free remission can be reached in a subset of RA patients following a structured DMARD tapering approach after being in stable long-term DMARD control. References: [1] Haschka J, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 2016 Jan;75(1):45-51. [2] Rech J, et al. Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment. Ann Rheum Dis 2016;75:1637-44. Disclosure of Interests: Larissa Valor: None declared, Melanie Hagen: None declared, Michaela Reiser: None declared, Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, Fabian Hartmann: None declared, Bernhard Manger: None declared, Georg Schett: None declared, 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), Koray Tascilar: None declared

Background Polyautoimmunity has been described to be associated with primary Sjogren’s syndrome (SjS) and the most frequent observed associated autoimmune diseases (AID) are autoimmune thyroid disease, autoimmune hepatitis and primary biliary cirrhosis, which are common organ-specific AID. In the same track, renal and lung involvement has increasingly been documented in SjS further highlighting its systemic nature. Objectives To describe and classify prevalence of polyautoimmunity and major organ involvement in a primary SjS-cohort. Methods This cross-sectional study included 179 patients [160 (89%) females and 19 (11%) males] diagnosed with primary SjS and fulfilling the ACR classification criteria (1) that had been admitted to our outpatient clinic between December 2008 and December 2018. Demographic and disease-specific characteristics were recorded in all patients. Results In our cohort the median age at diagnosis was 57 years (range: 20-85). Thyroid AID was found in 55/179 (30%) patients, with the following distribution: Hashimoto thyroiditis without (n=21) and with hypothyroidism (n=22), Graves’s disease without (n=4) and with thyroidectomy (n=8). Liver AID was detected in 8/179 patients (4%), 3 patients with autoimmune hepatitis and 5 patients with primary biliary cirrhosis. Regarding major organ involvement, 20/179 (11%) patients had renal manifestations: renal insufficiency (n=12), glomerulonephritis (n= 3), interstitial nephritis (n=2) and IgA nephritis (n=3). Eight/179 (4%) patients had lung manifestations: interstitial fibrosis (n=6), emphysema (n=1) and chronic obstructive pulmonary disease (n=1). Conclusion Our results add evidence for the presence of polyautoimmnunity and major organ involvement in SjS. We found a slightly lower prevalence of polyautoimmunity and major organ involvement compared to recently reported data (2). Nonetheless, extra-glandular organ involvement should be assessed in order to elucidate cumulative damage and how it might impact outcome, prognosis and therapeutic approaches in SjS. References [1] Shiboski SC, et al. American College of Rheumatology classification criteria for Sjogren’s syndrome: a data-driven, expert consensus approach in the Sjogren’s International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64(4):475-87. [2] Both T, et al. Reviewing primary Sjogren’s syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment. Int J Med Sci. (2017) 23;14(3):191-200. Disclosure of Interests Larissa Valor: None declared, Hannah Schenker : None declared, Melanie Hagen: None declared, Johannes Knitza: None declared, 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

Background:Preclinical models have indicated that biomechanical stress can trigger entheseal inflammation (1). Furthermore, enthesitis is a hallmark of psoriatic arthritis (PsA) and spondyloarthritis (SpA), suggesting that mechanoinflammation is an important step in their pathogenesis (2). However, the relation between mechanical stress and enthesitis in humans is poorly investigated. Competitive badminton is a demanding stop-and-go sport that strains entheseal sites in particular and provides an opportunity to assess the impact of physical activity on the development of an instant inflammatory response in the entheses.Objectives:To evaluate the influence of mechanical stress on the development of immediate enthesitis.Methods:BEAT (Badminton Enthesitis Arthrosonography Study) is an interventional study that assessed entheses in competitive badminton players before and immediately after a 60-minute intensive training session by ultrasound. Power Doppler (PD) signal and Gray-Scale (GS) changes were evaluated at the insertions sites of both Achilles tendon, patellar tendons and lateral humeral epicondyles and quantified using a validated scoring system (3). Pre- and post-training scores were compared using linear mixed-effects models. We used interaction terms to assess possible differential effects on patellar, elbow and Achilles entheses.Results:Thirty-two badminton players (22 men, 10 women) with an average age of 31.1±13.0 years were included (Table 1). On average, they had been playing badminton for 16.2±10.1 years. 192 entheseal sites were examined twice. The respective empirical total scores for PD examination were 0.1 (0.3) before and 0.5 (0.9) after training (Figure 1). Mean total GS scores were 2.9 (2.5) and 3.1 (2.5) before and after training, respectively. The mean total PD score difference of 0.4 between pre- and post -training was significant with a p value of 0.0014, whereas the p value for the mean total GS score difference of 0.2 was 0.63. Overall, seven participants (22%) showed an increased empirical total PD score. A mixed-effects model showed a significant increase of PD scores after training, with a mean increase per site of 0.06 (95%CI 0.01 to 0.12, p=0.017).Table 1.Baseline characteristicsDemographic characteristicsN, total32Females, N (%)10 (31.3)Age, years (mean ± SD)36.1 ± 13.0Height, cm (mean value ± SD)178.6 ± 9.9Body weight, kg (mean value ± SD)74.7 ± 13.5Smoking, N (%)11 (34.4)Alcohol, N (%)24 (75.0)Concomitant DiseasesInflammatory bowel disease, N (%)0Psoriasis, N (%) 0Uveitis, N (%)0Diabetes mellitus, N (%)0Hypertension, N (%)2 (6.3)Sports historyYears Badminton (mean ± SD)16.2 ± 10.1Figure 1.Ultrasound scores before and after training Figure 1. A Spaghetti plots depicting inividual Gray-Scale and Power Doppler ultrasound scores before and after trainingConclusion:Mechanical stress leads to rapid inflammatory responses in the entheseal structures of humans. These data support the concept of mechanoinflammation in diseases associated with enthesitis. However, while such responses may be self-contained in healthy subjects, they may be prolonged and more pronounced in certain risk groups, such as patients with PsA or SpA.References:[1]Cambré I, et al. Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nature Communications. 2018; 9:4613.[2]Schett G, et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017; 13:731-741.[3]Balint PV, et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Annals of the Rheumatic Diseases. 2018; 77:1730.Disclosure of Interests:David Simon: None declared., Arnd Kleyer: None declared., Sara Bayat: None declared., Johannes Knitza: None declared., Larissa Valor: None declared., Marina Schweiger: None declared., Georg Schett: None declared., Koray Tascilar: None declared., Axel Hueber Grant/research support from: Novartis Research Grant.

Background:Handheld ultrasound (HHUS) devices have increasingly found their way into clinical practice due to several advantages (e.g. portability, significantly lower purchase cost). However, there is no evidence to date on the accuracy and performance of HHUS in patients with inflammatory arthritis (IA).Objectives:To assess accuracy and performance of a new HHUS machine in comparison to a conventional cart-based sonographic machine in patients with IA.Methods:Consecutive IA patients of our outpatient clinic with at least one tender and swollen joint in the 66/68 joint count were enrolled. US was performed on clinically affected joints with corresponding tendons/entheses using a cart-based sonographic device (“Samsung HS40”) and a HHUS device (“Butterfly iQ”) in standard scan positions. One blinded reader scored all images for the presence of following pathologic findings: erosions, bony enlargement, synovial hyperthrophy, joint effusion, bursitis, tenosynovitis and enthesitis. In addition, synovitis was graded (B Mode and power Doppler (PD)) by the 4-level EULAR-OMERACT scale [1]. To avoid bias by the blinded reader, who otherwise would have been tempted to identify pathological findings for each examined joint, we also included 67 joints of two healthy volunteers into the evaluation. We calculated the overall concordance and the concordance by type of joint and type of pathological finding between the two devices (percentage of observation pairs in which the same rating was given by both devices). The Cohen’s kappa coefficient (κ) with 95% bootstrap confidence intervals was used to assess the agreement between the two US devices. We also measured the time required for the US examination of one joint with both devices.Results:32 patients (20 rheumatoid arthritis, 10 psoriatic arthritis, 1 gouty arthritis, 1 systemic lupus erythematosus) were included in this study. Mean age of patients was 58.2±13.7 years, 63% were females. In total 186 joints were examined. The overall raw concordance in B-mode between the two devices was 97 %, with an overall κappa for agreement of 0.90, 95% CI (0.89, 0.94). No significant differences were found in relation to type of joint or pathological finding examined. The PD-mode of the HHUS device did not detect any PD-signal, whereas the cart-based device detected a PD-signal in 61 joints (33%). The portable device did not offer any time saving compared to the cart-based device (mean time in seconds per examined region: 47 seconds for the HHUS device versus 46.3 seconds for the cart-based device).Conclusion:The HHUS device “Butterfly iQ” has been shown to be accurate in the assessment of structural joint damage and inflammation in patients with IA, but only in B-mode. Significant improvements are still needed to reliable demonstrate blood flow detection by PD mode.References:[1]D’Agostino, M.A., et al., RMD Open, 2017. 3(1): p. e000428.Table 1.Concordance between a handheld and a conventional cart-based US device in B-modeAgreement by siteN joints (%)Concordance (%)Kappa 95%CIOverall186970.90 (0.89 to 0.94)Wrist32 (17.2)960.86 (0.77 to 0.93)Finger/toe joint (MCP, PIP, DIP, MTP)114 (61.3)970.92 (0.88 to 0.95)Elbows11 (5.9)950.87 (0.75 to 0.97)Shoulder4 (2.2)1001.00 (NA to NA) *Knee20 (10.7)980.96 (0.90 to 1.00)Ankle5 (2.7)1001.00 (NA to NA) *Agreement by pathological findingJoint effusion950.81 (0.68 to 0.92)Synovitis940.87 (0.79 to 0.93)Synovitis OMERACT grade (0– 3)900.84 (0.76 to 0.91)Bone enlargement980.88 (0.71 to 1.00)Erosion980.89 (0.77 to 0.89)Tenosynovitis980.83 (0.61 to 0.96)Entheseopathy1001.00 (NA to NA) *Bursitis970.90 (0.89 to 0.94)* unreliable kappa statistics because of small number of shoulders/ankles examined and small number of entheseopathiesFigure 1.Pathological US findings in MCP joints (1, 2, 3) and wrist (4) depicted by the two different ultrasound devicesB-mode erosive (arrow) and synovial (asterisk) changes could be detected by both devices (1-2), while PD changes of different grades only by the conventional US device (3-4).Acknowledgements:This study was supported by the Deutsche Forschungsgemeinschaft (DFG- FOR2886 PANDORA and the CRC1181). Additional funding was received by the Bundesministerium für Bildung und Forschung (BMBF; project METARTHROS, MASCARA), the H2020 GA 810316 - 4D-Nanoscope ERC Synergy Project, the IMI funded project RTCure, the Emerging Fields Initiative MIRACLE of the Friedrich-Alexander-Universität Erlangen-Nürnberg, the Else Kröner-Memorial Scholarship (DS, no. 2019_EKMS.27) and Innovationsfond Lehre / FAU Erlangen-Nürnberg 2019.Disclosure of Interests:None declared

Background:Personalization of RA treatment is not optimal due to lack of predictors. We previously demonstrated in RA patients that central nervous system (CNS) pain response to tender joint compression, measured by using functional MRI (fMRI) of the brain rapidly wanes after 24 hours of anti-TNF administration and that a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumab-pegol (CZP)1,2. We therefore hypothesized that the CNS pain response upon compression of a painful joint could predict subsequent anti-TNF treatment response.Objectives:To compare disease activity after 12-weeks of CZP treatment to that of placebo in DMARD-refractory RA patients based on pre-treatment baseline CNS pain response measured using BOLD fMRI.Methods:Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28>3.2 under stable DMARD treatment for at least 3 months were eligible. Patients underwent fMRI scanning of the brain at screening for stratification by CNS pain response. Whole brain BOLD-signal-voxel-count of 700 units classifying between low and high, and were randomized to CZP or placebo (2:1) The primary outcome was low disease activity (LDA, DAS28 ≤3.2) after 12 weeks of treatment.Results:156 RA patients, inadequate responders to csDMARD, signed the informed consent. 139 patients (46/47, 46/49 and 42/43) (99 females, 71%) with moderate-high disease activity (mean (SD) DAS-28: 4.83 (1.03)) could be included respectively and completed the 12-week study treatment. Geometric mean (SD) numbers of baseline BOLD signal positive voxels were 559 (10), 81 (12) and 2498 (3) in the 3 arms respectively. The mean DAS28 (SD) scores after 12 weeks of study treatment were Placebo: 3.89 (1.29), CZP-L: 3.42 (1.06) and CZP-H: 3.06 (1.04). LDA was achieved in 12/47 patients (25.5 %) in placebo, 22/49 (44.9%) in the CZP-L, and 25/43, (58.1%) in the CZP-H arm. The linear effect term for the ordinal study group variable supported a linear trend of increasing CZP treatment effect with increasing baseline CNS pain response. RR (95% CI) for achieving LDA with each unit increase in treatment category over placebo was 1.79 (1.24 to 2.74, p=0.003).Conclusion:A higher pre-treatment brain activity in response to pain measured with fMRI predicts the chance of achieving low disease activity with CZP treatment.References:[1] Hess, A.et al.PNAS (2011)[2] Rech, J.et al. Arthritis & Rheumatism(2013).Acknowledgments :The study was supported by an unrestricted grant from UCB Biopharma SPRL, Brussels, BelgiumDisclosure of Interests:Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Hannah Schenker: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Melanie Hagen: None declared, Verena Schönau: None declared, Larissa Valor: 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, 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, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:Today approximately 50 percent of patients with RA reach sustained remission. In a specific subset of RA patients in stable remission, biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) may be successfully tapered. However, it remains challenging to predict the patients’ individual flare risk. As we have recently shown, machine learning based on extensive clinical and laboratory data could be used to estimate individual flare risk [1].Objectives:In this study we aimed to investigate the performance of machine learning models trained with variables that are typically (1) immediately available to a physician during patient visits (clinical and demographic variables without laboratory values and composite disease activity scores), (2) theoretically available to patients at home and (3) available to payers in large health-system databases.Methods:Longitudinal clinical data of RA patients on bDMARDs from the first interim analysis of the phase-3, multicentre, randomised, open, prospective, controlled, parallel-group RETRO study (EudraCT number 2009-015740-42) was used [2] to build a predictive model for estimating the flare probability within 3 months from the current patient visit. A flare was defined as a DAS-28 ESR score over 2.6. Four different models (log. regression, random forest, k-NN and naïve Bayes) were trained which output the flare probability at each patient visit. These probabilities were used as an input for a stacking logistic regression meta-classifier [3]. The final model performance expressed as the AUROC was assessed using nested cross-validation [4]. We applied this method to three variable subsets (physician, patient, payer, Table 1).Table 1.List of variables used in three subsets:Variable / RolePhysicianPatientPayerGender (m/f)xxxDisease duration (years)xxxMethotrexate co-use (yes/no)xxxOther DMARDs co-use (yes/no)xxxDrug ATC codexxxIV-administration (yes/no)xxxDose percentagexxxAgexxxBody mass indexxxxDose percentage changexxxSwollen joint countxTender joint countxVAS_GH (pat. global disease activity)xxHAQ (health assessment questionnaire)xxSmoking status (yes/no/ex)xxAlcohol consumption (yes/no)xxPrevious flares (yes/no)xResults:Data from 135 follow-ups of 41 patients were used. The measured AUROC of the best performing model using all RETRO variables was 0.802 (95%CI 0.717 – 0.887) [1]. When a subset based on demographic and clinical variables is used that is available to a physician immediately during a patient visit the AUROC drops about 5 percent points. When only variables theoretically available to patients at home are used, the performance drops about 10 percent points comparing to the original model. Similar observation holds for the variable subset typically available to payers (Figure 1).Conclusion:This study shows that predictive models for flares have the potential to support physicians in making decisions immediately during the patient visit, even though laboratory values and respective activity scores are not yet available. In the future, machine learning applications may allow fast and reliable decisions on flare prediction in RA patients. These data can guide decisions about DMARD tapering at in real time during the physician-patient contact and allow to reduce costs not only by selective treatment tapering but also by sparing additional laboratory examinations.References:[1] Vodencarevic A. et al. Arthritis Rheumatol. 2019; 71[2] Haschka J et al. Ann Rheum Dis 2016; 75:45-51.[3] Tang J et al. CRC Press 2015; 498-500[4] Cawley GC et al. J Mach Learn Res 2010; 11:2079-2107Disclosure of Interests:Asmir Vodencarevic Shareholder of: Siemens Healthcare GmbH. Siemens Healthcare GmbH is a medical technology company (NOT a pharmaceutical company)., Employee of: Siemens Healthcare GmbH. Siemens Healthcare GmbH is a medical technology company (NOT a pharmaceutical company)., Koray Tascilar: None declared, Fabian Hartmann: None declared, Michaela Reiser: None declared, Sara Bayat Speakers bureau: Novartis, Johannes Knitza Grant/research support from: Research Grant: Novartis, Larissa Valor: None declared, Melanie Hagen: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, 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, Marcus Zimmermann-Rittereiser Shareholder of: Siemens Healthcare GmbH. Siemens Healthcare GmbH is a medical technology company (NOT a pharmaceutical company)., Employee of: Siemens Healthcare GmbH. Siemens Healthcare GmbH is a medical technology company (NOT a pharmaceutical company)., Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly

Background The efficacy of Golimumab treatment in psoriatic arthritis (PsA) patients has been widely documented. Objectives The aim of this study was to analyse the long-term retention rate of golimumab and to identify independent predictors of drug retention in patients with PsA including concomitant synthetic disease-modifying antirheumatic drugs (sDMARD) Methods Prospective monocentric cohort of PsA patients treated with golimumab according to clinical practice. Study was approved by local Ethics Committee. Demographic and clinical variables were analysed with Cox proportional hazard regression model. Results 48 patients were included, 20/48 (41.7%) oligoarticular, 19/48 (39.6%) polyarticular and 9/48 (18.7%) with peripheral and axial PsA. The baseline characteristics of the patients are shown in table 1. Follow-up time was 89.25 patients-year. Mean survival time was 40.3 months (95% CI: 32.0–48.5). Age, mean evolution time and previous biological use were significant in the univariate analysis. Concomitant sDMARD had no influence on golimumab retention rate (HR: 1.3; 95% CI: 0.5–3.2; p: 0.6). Figure 1. When golimumab was used as first or second biologic treatment, it had a better retention rate than when it was used as third or fourth, but did not reach statistical significance (HR: 2.3; IC 95%: 0.8–6.2; p=0.1). 18/48 patients (37.5%) withdrew golimumab treatment. 13/18 (72.2%) due to lack of efficacy, 1/18 (0.6%) due to adverse events and 4/18 (22.2%) due to other reasons. Conclusions Real-world Golimumab retention rate in patients with PsA was good and did not depend on concomitant treatment with sDMARD. When used as first or second biologic, Golimumab retention rate tended to be better. Disclosure of Interest None declared

Background Inflammatory myopathies (IIM) are a heterogeneous group of autoimmune rheumatic diseases characterized by muscle inflammation and progressive weakness. They include any kind of primary inflammatory muscle disease that is not otherwise better explained by metabolic, toxic, infectious, neurologic or inherited causes. The presence of autoantibodies (AA) in IIM is variable and they can recognize nuclear and cytoplasmic cellular components. Objectives To evaluate the AA profile in patients diagnosed with IIM. Methods We evaluated 479 patients that included 12 hospitals belonging to the IIM registry of the Rheumatology Society in Madrid (SORCOM-REMICAM) with diagnosis from January 1980 to December 2014. All patients were diagnosed of IIM according to Bohan and Peter criteria. The AAs evaluated were ANA (n=476), anti-Jo1 (n=457), anti-RNP (n=427), anti-MI2 (n=159) and ACA (n=293), according to the standard techniques in the respective laboratories. The presence of ANA was considered valid with at least two positive determinations. The AAs were compared according to the classification I) as dermatomyositis (primary and secondary dermatomiositis) (DM) and polymyositis (PM) including the rest of the patients. Also, IIM were classified (II) as primary polimiositis (PPM), primary dermatomyositis (PDM), overlap syndrome (OSd), juvenile myopathies (JM), cancer-associated myopathies (CAM), autoimmune necrotizing myopathy and inclusion body myositis (these were grouped as other myositis; OM). Results In the PM and DM groups 250 and 229 (52.2% and 47.8%) patients were included respectively. Positive ANA, anti-Jo1 and anti-RNP were higher in the PM than in the DM group (67, 22 and 19% vs. 56, 11 and 6%) (p=0.21, p=0.002, p=0.0001, respectively). The presence of anti-MI2 was higher in the DM group (p=0.024), according to the classification II, we found statistically significant differences in ANA, anti-Jo1, anti-RNP and anti-ACA. The OSd group had the highest proportion of ANA, anti-RNP and ACA positive AA and the JM group had the lowest frequency of Anti-Jo1 (see Table 1). Conclusions The AA associated with the IIM subtypes is consistent with published scientific evidence on other cohorts for ANA, anti-Jo1, anti-RNP and anti-MI2, in spite of the small sample size. The OSd group showed higher ANA and anti-RNP frequencies which might be explained by the coexistence of SLE and MCTD patients. It could be interesting to follow up those PPM patients with positive AA because they could be in the future diagnosed with a connective tissue disease. Carrying out longitudinal studies that include a greater proportion of patients may help to evaluate and predict the clinical course of IIM. References Bohan A, Peter JB. N Engl J Med 1975 Feb 13;292(7):344–7. Acknowledgements . Disclosure of Interest None declared

Background The major SARD have an increased mortality compared to the general population. It is well known that the main causes of death in Systemic Lupus Erythematosus (SLE) are infections (INF), cardiovascular events (CV), neoplasia (NEO) and disease activity. However, the compared mortality of Mixed Connective Tissue Disease (MCTD), Systemic Sclerosis (SSc), Poly/Dermatomyositis (PM/DM), overlap syndromes (OS), Sjogren9s syndrome (SS), Antiphospholipid syndrome (APS), systemic vasculitis (SV), and undifferentiated or incomplete Connective Tissue Disease (UCTD) is poorly described. Objectives To analyze the causes of death and the autoantibodies (AAB) profile among the SARD. Methods This was a single center, prospective and observational study. Mortality by all causes and relationship with AAB profile were analyzed in patients diagnosed of SLE, MCTD, SSc, PM/DM, OS (simultaneous or sequential criteria of 2 or more SARD), SS, APS, SV and UCTD or incomplete SARD (at least one clinical criterion of the classification criteria and a related antibody of any of the SARD). Data were obtained from the “Systemic Autoimmune Rheumatic Diseases Registry” of a tertiary referral hospital from 1986 to 2016. Patients with rheumatoid arthritis were excluded. The SARD registry counts with the institutional review board approval. Results 1750 patients were included, of whom 1453 (83%) were women. Five hundred fifty six SLE, 125 SSc, 111 PM/DM, 91 OS, 90 MCTD, 250 SS, 71 APS, 211 SV, 117 UCTD and 128 losses to follow-up, the global follow up rate was 92.7%. A global mortality of 350 (20%) cases was observed: 101 INF (28,8%), 89 CV (25,4%), 51 NEO (14,5%), 45 due to disease activity (12,8%), 41 other causes (11,7%) and 23 from unknown causes (6,5%). Table 1 shows detailed mortality causes compared by diseases. A higher mortality was associated (p Conclusions The main causes of death among SARD patients are CV (MCTD, SLE, and SSC), severe infections (OS, SV, and PM/DM), disease activity (APS) and neoplasia (SS). A higher mortality is observed among ANCA positive SV, anti-topoisomerase I positive SSC, MCTD, OS, anticardiolipin and myositis-specific positive patients. Disclosure of Interest None declared

Background The determination of fibromylagia (FM) in patients presenting diffuse, chronic arthritis is fraught. The Fibromyalgia Rapid Screening Tool (FiRST) is a validated questionnaire with high sensitivity and moderate specificity shown to be able to identify up to 89% of FM cases, even when accompanied by anxiety, depression or functional disability. Decisions to embark upon a course of full or tapered biological disease-modifying antirheumatic drugs (bDMARD) are influenced in part by patient self-assessment scores as well as concomitant pathologies. Objectives To evaluate the prevalence of FM using the FiRST questionnaire in bDMARD-treated chronic arthritis patients. Methods This cross-sectional study included 325 patients [178 (54,8%) females and 147 (45,2%) males] diagnosed with chronic arthritis and treated with bDMARD. Patients were consecutively recruited from the Biological Therapy Unit from January to March 2015 all having undergone full or tapered bDMARD for at least 1 year. Dosage tapering had been applied to patients considered to be in remission. All patients self-completed the FiRST questionnaire with a score>5/6 considered positive. Clinical assessment was carried out by one specialist only. Demographic, clinical and laboratory variables were recorded with pathology-specific indices used to assess disease status, i.e.DAS28-ESR, DAS28-CRP, SDAI, CDAI, BASDAI, BASFI, ASDAS-CRP. Patient pathologies were classified as peripheral arthritis (PerAR: RA, PsA, PerSpA) or axial spondyloarthropathy type (AxSpA). Results A total of 68/325 (21%) patients scored >5/6 in the FiRST. Disease duration and previous bDMARD usage were not significant regarding scores 5/6, respectively (p=NS). Fifteen per cent of patients with tapered bDMARD registered scores >5/6 against 85% of patients in full bDMARD dosage (p=0.001). There were a higher number of remission patients in the PerAR group as defined under DAS28-ESR, SDAI and CDAI [(96%, 94% and 94%) (p=0.01, p=0.04, p=0.032), respectively]. Association was found in the PerAR subgroups between tapered bDMARD and remission in RA patients only, as defined under DAS28-VSG, SDAI and CDAI (p=0.026, p=0.04, p=0.043, respectively). In the AxSpA tapered bDMARD subset, 86% of patients were considered to be in clinical remission as set out under BASDAI (p=0.019). Conclusions No difference was observed between the PerAR and AxSpA groups for FiRST>5/6. Fewer patients undergoing tapered bDMARD dosage recorded FiRST scores >5/6. Therefore, early identification of chronic arthritic patients presenting FiRST>5/6 may prove to be an important step in furthering understanding of clinical activity in diffuse arthritis as well as offering improved diagnostic and therapeutic outcomes to bDMARD-treated patients with possible concomitant FM. Disclosure of Interest None declared

Background Lung fibrosis (LF) is a type of interstitial disease that leads to lung scarring, respiratory failure and later on, death. There are 2 main types of LF: idiopathic and secondary; and the prognosis is very different. LF becomes relevant in connective tissue diseases (CTD) and some studies have suggested that there could be an association between anti-Ro/TRIM21 antibodies and the development of interstitial lung disease in these patients. Objectives The aim of this study was to assess if the presence of anti-Ro52/TRIM21 antibodies is an independent risk factor for developing CTD-associated LF. We also aimed to evaluate the initial manifestations of systemic diseases and clinical characteristics linked to certain antibodies. Methods It is a prospective, observational, longitudinal, single-center study conducted among unselected patients with CTD (rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM), overlap CTD syndrome (OCTD), MCTD, primary Sjogren9s sd (PSS), primary antiphospholipid sd, systemic vasculitis, and undifferentiated connective tissue disease). We analysed data from 1,432 caucasian patients included in the “Systemic Autoimmune Diseases (SAD) Registry” from 1988 to 2014. They were all checked at least biannually and blood samples were taken according to clinical practice. Exclusion criteria were LF as the initial manifestation of the SAD, LF already diagnosed at the first visit and also LF secondary to drugs or a specific environment. Results 10% of patients included in the study developed LF. The OR for LF in patients with anti-Ro52/TRIM21 antibodies was 1.757 (95%CI=1.1–2.7). The OR for LF increased with every year of age (OR=1.03, 95%CI=1.02–1.04). Only 9 out of 146 patients with LF were positive for Anti-La/SS-B antibodies, and the OR for males was 8.6 compared to women (95%CI=1.8–39.5). Patients with SSc and PM showed a higher OR for the development of LF (6.9 95%CI=4.6–10.4 and 2.0, 95% CI=1.2–2.8 respectively) compared to those diagnosed with other CTD. The time passed from the first symptoms to the diagnosis of LF was inversely related to the age of onset (r=-.230; p=0.013). The average time was 60 months for patients with anti-Ro52/TRIM21 antibodies (29 patients) and 138 months for patients without them. Conclusions Anti-Ro52/TRIM21 antibodies have been proved to be a risk factor for developing LF. The earlier the age of onset, the slower the progression to fibrosis. However, patients with anti-Ro52/TRIM21 antibodies tend to have a faster development, independent of the age of onset. Anti-La-SS-B antibodies seem to be a protective factor for the development of LF in both genders; but the association is stronger in women. Disclosure of Interest None declared

Background Mixed Connective Tissue Disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterized by clinical manifestations of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and polymyositis (PM) and the presence of anti-U1-RNP antibodies. Objectives To determine whether there are patients with symptoms of MCTD in the absence of anti-U1-RNP antibodies. Methods This was a monocentric, prospective, observational study of patients with SARD. All patients diagnosed of MCTD according to Kasukawa and/or Alarcόn-Segovia9s criteria, SLE, SSc, PM, overlap syndromes (simultaneous or sequential criteria of 2 or more SARD), Sjogren9s syndrome, Antiphospholipid syndrome, systemic vasculitis and undifferentiated or incomplete SARD (at least one clinical criterion of the classification criteria and a related antibody of any of the SARD) were included in the “Autoimmune Systemic Rheumatic Diseases Registry” of the Hospital General Universitario Gregorio Maranon Rheumatology Department from 1986 to 2012. The registry includes 2406 patients diagnosed with SARD. Patients with rheumatoid arthritis were excluded. Patients with clinical MCTD criteria were divided into seropositive (MCTD, with anti-U1RNP) and seronegative (possible MCTD, without anti-U1RNP). The registry counts with the local Institutional Ethics Board approval. Results A total of 692 patients were recruited, 608 women (87.9%). Seventy (70, 10.1%) patients were classified as seropositive and 75 (10.8%) as seronegative by Kasukawa9s criteria. Sixty-two (62, 8.9%) patients were classified as seropositive and 54 (7.8%) as seronegative according to Alarcόn-Segovia9s criteria. There were no significant differences in age at disease onset, age at diagnosis or disease duration (p>0.05) between seropositive and seronegative patients. Seropositive patients with Kasukawa9s criteria presented more frequently: lymphadenopathy, malar rash, leukopenia, Raynaud9s phenomenon, muscle weakness and increase of muscle enzymes (Table 1). By Alarcόn-Segovia9s criteria, patients who developed myositis were more frequent in the seropositive group (p=0.007, OR 3.25, 95% CI, 1.44–7.32). Conclusions Some patients with SARD manifestations fulfill MCTD clinical criteria, both Kasukawa9s and Alarcόn-Segovia9s, in the absence of anti-U1-RNP antibodies from the onset of the disease and throughout its evolution (seronegative MCTD). The frequency of seronegative MCTD was similar to the frequency of seropositive MCTD. Patients with seropositive MCTD presented more frequently manifestations of SLE (lymphadenopathy, malar rash and leukopenia) when using Kasukawa9s criteria and of PM when using both criteria. Disclosure of Interest None declared

Background Idiopathic inflammatory myopathies (IIM) comprise a heterogeneous group of autoimmune conditions. Joint involvement can be considered to be part of the IIM systemic manifestations, together with a possible gastrointestinal, cardiovascular and/ or pulmonary involvement. Although articular involvement in the IIM has been described as variable and non-specific with a chronic course it might be an early symptom of dermatomiositis in up to 30% of cases and in those patients with overlap syndromes. Objectives To evaluate and to identify joint manifestations in IIM patients. Methods We evaluated a cohort of 479 patients that included 12 hospitals in the Community of Madrid belonging to the IIM registry of the Society of Rheumatology of Madrid (SORCOM-REMICAM) with diagnosis from January 1980 to December 2014. All patients were diagnosed of IIM according to Bohan and Peter criteria (1). The presence of arthralgia and arthritis was considered. IIM were classified as dermatomyositis (primary and secondary dermatomiositis) (DM) and polymyositis (PM) including the rest of the patients (classification I). Also, IIM were classified (II) as primary polimiositis (PPM), primary dermatomyositis (PDM), overlap syndrome (OSd), juvenile myopathies (JM), cancer-associated myopathies (CAM), autoimmune necrotizing myopathy and inclusion body myositis (these were grouped as other myositis; OM). Results We found 70 (18%) patients with acute arthritis ( 6 weeks) and 245 (65%) patients without any joint manifestations. Using the Tanimoto et al. criteria (1), the presence of erosive arthritis was observed in 149/479 (38.3%) of the patients. When comparing the joint manifestations in the PM and DM groups (n=250, 52.2% vs. n=229, 47.8%) no statistically significant differences were observed. However, assessing joint manifestations according to classification II, we observed that the highest prevalence was found in the OSd group, followed by the PDM group (p=0.0001). The group with less joint manifestations was JM compared to OSd and PDM (Table 1. Conclusions The presence of joint manifestations associated with IIM in our cohort is higher compared to other studies described in the literature so far and emphasize the importance of an accurate joint examination in these patients. The OSd group showed more joint manifestations which might be explained by the coexistence of SLE and MCTD patients in this group. Currently, no association between the clinical subtypes of IIM, overall, these results are encouraging and suggest that joint assessment in follow up may be helpful in differentiating subtypes of IIM. References Bohan A, Peter JB. N Engl J Med 1975 Feb 13;292(7):344–7. Disclosure of Interest None declared

Background Assessment of nail involvement is currently made by clinical assessment using nail psoriasis severity index (NAPSI). Whilst clinical assessment can detect superficial nail changes, the matrix and the extensor tendon region are not accessible for clinical assessment. Musculoskeletal (MS) ultrasound (US) is playing an important role in the evaluation of psoriatic arthritis (PsA) patients. Recently, MSUS has been more used in the evaluation of nail involvement in psoriasis (Pso) and PsA patients. Objectives The primary objective of this observational, cross-sectional study was to assess the MSUS morphological and vascular abnormalities in nail in PsA and Pso patients compared with healthy controls. The secondary objective was to compare MSUS and clinical assessment of the nail in PsA and Pso patients. Methods We included patients with PsA (diagnosed according to CASPAR criteria) and patients with Pso without joint involvement (diagnosed by an experienced dermatologist according to clinical findings) and healthy controls. Clinical evaluation consisted in the evaluation of the NAPSI and PASI scores. The MSUS evaluation consisted in the evaluation of 10 hand nails. In B-mode (BM) we evaluated the followings: thickness of the nail bed from the distal phalanx bone surface to the ventral plate (PB) according to Worstman X et al.; thickness of the nail from dorsal to ventral plate (IP); dorsal and ventral plate morphology, echogenicity and integrity. Additionally, we performed a color Doppler (CD) evaluation for the presence of CD signal at the nail bed and matrix level. A score for BM and different scores for CD were calculated for each nail and sums of all nails for BM and CD scores were calculated for each patient. Results We evaluated 60 patients with PsA, 23 with Pso and 20 controls. 52.4% were female. The mean age (SD; range) was 50.2 (13.6; 23–83). The age was higher in patients (Pso and PsA) than in controls (p US measurements of IP and PB were significantly higher in patients than in controls in the majority of the nail (p Overall we found weak to moderate positive correlations between NAPSI and US scores for BM, both for matrix and bed. For most of the nails we found no correlation between NAPSI and CDUS scores; for the rest of the nails the correlation was weak, both positive and negative. References The MSUS measurements and scores showed to be higher in patients with PsA and Pso compared with controls, while CD scores showed no differences. Disclosure of Interest None declared

Background Suppurative Hidradenitis (SH) is an inflammatory skin disease which often responds poorly to treatment. It is a disorder of the apocrine glands (axillary, inguinal and anogenital regions) that can result in infection, inflamed nodules, cysts, abscesses and sinus tracts. There is a 1–4% incidence of SH in patients with spondyloarthropathies and inflammatory bowel disease, possibly due to innate immune system deregulation. The use of biological disease-modifying antirheumatic drugs (bDMARD), specifically tumor necrosis factor inhibitors, has been useful in cases when other therapies fail. Objectives To evaluate the prevalence of SH using the SH-questionnaire in bDMARD-treated chronic arthritis patients. Methods This cross-sectional study included 325 patients diagnosed with chronic arthritis. Patients were recruited consecutively from the Biological Therapy Unit of the Hospital General Universitario Gregorio Maranόn and evaluated from January to March of 2015. All patients had been undergoing full or tapered bDMARD treatment for at least 1 year and none had any history of SH. Those patients deemed to be in clinical remission were on tapered bDMARD dosage. All patients self-completed the validated SH-questionnaire (1) which was considered positive when one answer was affirmative and when lesions presented in >1 anatomical location. Patient pathologies were subclassified into 2 groups: i) peripheral arthritis (PerAR) which includes rheumatoid arthritis (RA), psoriatic arthritis (PsA) and peripheral spondyloarthropathies (PerSpA); ii) axial spondyloarthropathies (AxSpA). Clinical evaluation was performed by the same physician for all patients. Demographic, clinical and laboratory variables were recorded and disease status was assessed through the relevant clinical index, i.e.DAS28-ESR, DAS28-CRP, SDAI, CDAI, BASDAI, BASFI, ASDAS-CRP. Results SH-positive was observed in 25/325 (7.7% vs. 92.3%) patients. Of these 25 patients, 12 (48%) were female and 13 (52%) male. Mean age was 52 years (SD±12.9) and mean time since diagnosis was 14 years (SD±9.3). Twenty-four out of 25 patients were undergoing anti-TNF treatment (ETN=10, GOL=7, ADL=6, CTZ=1). Eighty-four per cent of patients were undergoing full bDMARD dosage with the remaining 16% on tapered. By subset pathology, 13 SH positives were PerAR type and 12 were AxSpA (5.8% vs. 11.8%, p=0.062). On analysis of PerAR subtypes, we found 6 patients had PsA and 5 RA. Evaluating clinical disease activity, we found 9/13 patients in the PerAR group to be in clinical remission according to DAS28-ESR and CDAI (p=0.02 for both). Additionally, we found only 4/12 patients in remission in the AxSpA group as defined under BASDAI, BASFI and ASDAS-CRP (p=0.006, p=0.005, p=0.004, respectively). Conclusions We found more SH-positives in the AxSpA than in the PerAR group, which is consistent with published data. A bDMARD tapered dosage was related to SH-positivity which might be linked to persistent and undetectable chronic inflammation. References Esmann S, et al. Br J Dermatol. 2010 Jul;163(1):102–6. Disclosure of Interest None declared

Objectives To compare power Doppler (PD) vs colour Doppler (CD) semiquantitative and quantitative scoring of synovial vascularization (RA) and to evaluate the relationship between semiquantitative and quantitative scores in patients with rheumatoid arthritis (RA). Methods One hundred RA patients underwent B-mode, PD, and CD assessments of 12 joints at two European centres. Each joint with synovial hypertrophy detected on B-mode was semiquantitatively scored (0–3) for PD (SPD score) and CD (SCD score) synovial signal. PD and CD synovial signal were also quantitatively scored (0–100%) (QPD and QCD scores, respectively) using a software for counting the colour fraction. Results We found SH in 184 joints. SPD and SCD agreed in 92.3% (95% CI: 88.4; 96.2%) of paired scores, with Kendall rank correlation coefficient tau-b=0.95. Significant differences between marginal distributions of SPD and SCD were not found (p=0.565). QPD and QCD scores were highly correlated (Pearson9s coefficient=0.70) but Blamd-Altman plot showed insufficient agreement, being the QCD scores systematically slightly higher than the QPD scores. The distribution of QPD and QCD values between SPD and SCD scores, respectively, showed significant differences between grade 0 and grade 1 (p Conclusions SPD and SCD scores were concordant and QPD and QCD scores highly correlated although were not concordant. There was consistency between SPD and SCD moderate and severe scores and QPD and QCD scores. There was an overlapping between SPD and SCD mild and moderate scores regarding QPD and QCD scores. Disclosure of Interest None declared

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin characterized by a hypercoagulable state and a high mortality rate. Mechanisms that cause the accelerated deterioration of cardiovascular health in SLE are unknown. Objectives: to characterize the prothrombotic state in SLE patients by global coagulation assays and the contribution of platelets, endothelial damage, microparticles and neutrophil extracellular traps (NETs) in their prothombotic profile. Material and methods: 72 patients and 90 healthy controls were recruited. Patients were classified according to clinical characteristics in: 32 with lupus (SLE group), 29 with SLE and antiphospholipid antibodies (aFL, SLE+aFL group) and 12 who met the criteria for SLE and antiphospholipid syndrome (APS, SLE+APS group). Experimental protocol was approved by La Paz University Hospital Ethics Committee. Venous blood collected in BD sodium citrate tubes (3.2%) was centrifuged at 150 g for 20 min at 23ºC to obtain platelet-rich plasma (PRP). PPP was obtained by centrifugation at 1500 g for 15 min at 23ºC. To obtain neutrophils, whole blood was centrifuged to 1600 rpm 25 min using a Ficoll gradient and red cells were lysed. Rotational thromboelastometry (ROTEM®) was performed in naTEM condition. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds]); alpha angle (tangent to the curve at 2-mm amplitude [in degrees]), Ax (clot firmness at time x, [in mm]) and maximum clot firmness (MCF, [in mm]) were recorded. Procoagulant activity associated to microparticle's content of tissue factor was determined in PPP by Calibrated Automated Thrombogram (CAT) using MP-reagent (4 mM phospholipids, Diagnostica Stago, Spain). We evaluated the endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced) and the time to the peak. Thrombin generation associated to NETs was also measured by CAT. Neutrophils from healthy controls or from LES patients were stimulated with 100 nM PMA in RPMI medium during 45 min at 37º and then cocultivated with PRP adjusted to 105 platelets/µL. NETs formation was verified by fluorescent microscopy performed with DAPI and an anti-myeloperoxidase antibody. Plasma levels of LDL-ox, E-Selectin and PAI-1 were determined by Elisa (R&D Systems, MN, USA and Affymetrix eBioscience, Vienna, Austria, respectively). Platelet activation was analysed by flow cytometry (FCM, FACScan, BD Biosciences). Fibrinogen receptor activation was evaluated through PAC1-FITC binding and release of granule's content was assessed with monoclonal antibodies (mAbs) anti-CD63 and anti P-selectin in quiescent and 100 µM TRAP and 10 µM ADP stimulated platelets. Data were analysed with Graphpad prism and p ≤0.05 was stablished as statistical significance. Results: PAI-1 plasma level was increased in all patient's groups, whereas LDL-ox and E-selectin showed no differences with control cohort (Fig.1). ROTEM demonstrated a procoagulant profile in SLE and SLE+aPL but not in SLE+APS group (Fig. 2). PAI-1 levels correlated with several ROTEM parameters (Table 1). SLE patients and SLE+aFL showed a basal platelet activation. Moreover, SLE group exposed more P-selectin and CD63 than controls (Fig.3). Regarding thrombin generation associated to tissue-factor content of microparticles, no differences were observed between SLE patients and healthy controls. On the other hand, SLE patients had an increased peak of thrombin generation related to NETs formation (control group: 170.3± 58.0, SLE patients: 230.6±39.3, p=0.019). Conclusions: ROTEM® detected a hypercoagulable state in SLE and SLE+aPL patients. The hypercoagulable state might be linked to increased PAI-1 plasma levels and basal platelet activation in SLE and SLE+aPL groups. Moreover, neutrophils from SLE patients seemed to present a basal activation that induced a NETs-related procoagulant state in these patients. SLE+APS patients did not show a hypercoagulable state perhaps because of the presence of lupus anticoagulant and/or to therapeutic treatment of these patients. This work was supported by grants from the FIS-FONDOS FEDER (PI15/01457, NB). NVB holds a Miguel Servet tenure track grant from FIS-FONDOS FEDER (CP14/00024). Disclosures Fernandez-Bello: Novartis, Pfizer, ROCHE, Stago: Speakers Bureau. Robles:ABBVIE, SANDOZ FARMACEUTICA: Speakers Bureau. Álvarez Roman:Sobi: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau. Canales:Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Speakers Bureau; Sandoz: Honoraria; iQone: Honoraria; Takeda: Speakers Bureau; SOBI: Research Funding; Karyopharm: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau. Jimenez-Yuste:Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, Shire: Consultancy, Honoraria, Other: reimbursement for attending symposia/congresses , Research Funding, Speakers Bureau. Butta:Novartis: Consultancy; Roche, Pfizer: Speakers Bureau.

Introduction: Mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) appear to be multifactorial: autoantibodies, autoreactive CD8+ cytotoxic T cells, enhanced apoptosis and loss of sialic acid which mediates platelet clearance through the Ashwell-Morell receptors present in hepatocytes. Differential involvement of each of them might condition the ability of patients with ITP to respond to treatments. We aimed to examine platelet features and the immunological state of patients with ITP who do not respond to any treatment to detect the unique characteristics of this group. Methods: This was an observational, prospective and transversal study. Patients with chronic primary ITP were included: 28 ITP patients without treatment for at least 6 months (UT-ITP); 36 responders to agonists of thrombopoietin receptors (TPO-RA); and 14 ITP patients who did not respond to first- and second-line treatments (NR-ITP). A healthy control group (n=104) was also included in the study. Active caspase-3, -7, -8 or -9 were determined by flow cytometry using CaspaTag kits (Millipore, Madrid, Spain) in PRP diluted with HEPES-buffer containing 2 mM Ca2+ and 2 mM Gly-Pro-Arg-Pro (Sigma-Aldrich, Madrid, Spain) to prevent fibrin formation . Platelet surface glycan exposure was analysed by determining the binding of lectins by flow cytometry. To do so, washed platelets were incubated with 1 μg/ml Alexa fluor 488-conjugated wheat germ agglutinin lectin (WGA, Invitrogen, Spain) or with 1 μg/ml FITC-conjugated Ricinus communis agglutinin (RCA, Vector Labs, UK). WGA binds to sialic acid and N-acetylglucosaminyl residues, and RCA is a galactose-specific legume lectin which binding serves as an indirect measurement of the loss of sialic acid. Peripheral blood mononuclear cells (PBMCs) subsets were analysed by flow cytometry using specific antibodies. Experimental data was analysed using SPSS 9.0 software (SPSS Inc., Chicago, IL). Results: Platelets from TPO-RA treated and from NR-ITP patients had increased caspase-3, -7, -8 and -9 activities (Figure 1A). Platelets from NR-ITP patients exposed less sialic acid and more N-acetylglucosaminyl residues than the other groups (Figure 1B). Binding of WGA and RCA correlated with caspase activities (Table 1). Distribution of lymphocytes, monocytes and natural killer cells is shown in Table 1. NR-ITP patients had an increased proportion of B lymphocyte (LB), maybe due to a significant rise in the fraction of naive LB cells, and a diminution in LTreg subset. Whereas classical monocytes was increased, nonclassical monocyte fraction was decreased in the UT-ITP and NR-ITP groups. NR-ITP patients also presented an increased CD16+CD56bright cells fraction and a diminished NK CD16+CD56dim subset. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls (monocyte and NK cells subset distribution and LTreg count similar to control group). It is of interest to note the relationship between loss of sialic acid from platelet surface glycans and Tregs count: the most reduced surface exposure of sialic acid, the less Treg count (Figure 2). Conclusions: Platelets from NR-ITP patients had more signs of apoptosis and a different composition of surface glycans, accompanied by a diminished LTreg population, a higher LB naïve percentage, and an increased CD16+CD56bright cells fraction in circulation, indicating a severe deregulation of the immune system. Since an inverse correlation was observed between loss of sialic acid and LTreg count, a potential relationship between glycan composition on the platelet surface and immune response is suggested, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP. On the other hand, TPO-RA appears to have a beneficial effect on immune response. Nevertheless, one of the limitations of our study was that patients were recruited once the response to TPO-RA was achieved; therefore, a longitudinal study would provide more information regarding TPO-RA effects. This work was supported by grants from the FIS-FONDOS FEDER (PI15/01457, NB). NVB holds a Miguel Servet tenure track grant from FIS-FONDOS FEDER (CP14/00024). Disclosures Álvarez Roman: Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau. Fernandez-Bello:Novartis, Pfizer, ROCHE, Stago: Speakers Bureau. Martín:SOBI: Research Funding; Novartis, Pfizer, ROCHE, Novo Nordisk: Speakers Bureau. Rivas Pollmar:Novartis, Pfizer, ROCHE, Novo Nordisk: Speakers Bureau; SOBI: Research Funding. Canales:Novartis: Honoraria; Takeda: Speakers Bureau; iQone: Honoraria; Sandoz: Honoraria; Celgene: Honoraria; SOBI: Research Funding; Karyopharm: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Gilead: Honoraria; Janssen: Honoraria, Speakers Bureau. Jimenez-Yuste:Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, Shire: Consultancy, Honoraria, Other: reimbursement for attending symposia/congresses , Research Funding, Speakers Bureau. Butta:Novartis: Consultancy; Roche, Pfizer: Speakers Bureau.

Heart diseases are one of the most common ailments that subtly kill its victim within seconds. The lack of knowledge about one's heart rate is one of the common reasons why it successfully penetrates the victim's heart at stealth. Portable monitoring device became a trend in the field of medicine for various benefits and ease for the user; it avoids the hassle in going to hospitals, coping up with check-up schedules, and paying huge amount of money just to have a close monitoring of one's heart activity. The portable heart rate monitoring device was created to give the patient the ease in monitoring their heart rate with the use of their smartphones, which are connected via live Bluetooth connection, using Bluetooth Shield 4.0. The monitoring sessions' output is accurately and reliably aligns with the heart rate monitoring devices used in hospitals, which are proven through a series of (1) accuracy test, (2])reliability test, and for the SMS feature, (3)the accuracy of SMS notification upon reaching the threshold, and (4) the Bluetooth range between the device and the smartphone. The sessions can be stored and retrieved from the memory of the smartphone itself. It can also be used to closely monitor the heart rate at a real time basis on a certain period of time. The device can be used within 10 m. radius away from the smartphone and can utilize the SMS notification feature using the regular load of the phone's SIM card.

Summary Development of polyfunctional T lymphocyte responses is critical in the immunological response against HIV-1. Fifty-four HIV-1 infected patients receiving antiretroviral treatment (ART) and immunization with an HIV-1 immunogen or placebo, periodically every 3 months throughout a period of 36 months, were evaluated for the purposes of analysing the development of HIV-1-specific CD4 + and CD8 + responses. A significant increase of proliferating and IFN-γ producing CD8 + HIV-1-specific T cells, of HIV-1-specific precursor frequencies for CD8 + and for CD4 + T cells and of Gag/pol-specific memory CTL precursors (CTLp) was observed in the immunogen group in comparison to placebo. IL-2 intracellular expression and IFN-γ and TNF-α co-expression in HIV-1-specific CD8 + T cells were also substantially increased in the immunized group. A negative correlation between viral load and CD3 + CD4 + CFSE low HIV-1-specific lymphoproliferative response and frequency of Gag/pol-specific CTLp was solely observed in the HIV-1 immunogen group. Long-term immunization in patients receiving ART helps to develop HIV-1-specific polyfunctional T cell responses.

Background: Rapid screening for the detection of HLA-B*57:01 in the prevention of abacavir hypersensitivity in HIV-1-infected patients is a hallmark for clinical services. Objective: The aim of this work was to analyze the utility of flow cytometry with a new FITC-conjugated B-17 monoclonal antibody (mAb3E12) for HLA-B*57:01 screening in a Spanish cohort of 577 HIV-1+ individuals. Methods: Cryopreserved peripheral blood mononuclear cell samples from HIV-1+ individuals were analyzed by flow cytometry with the mAb 3E12 that recognizes both HLA-B*57 and HLA-B*58 alleles (members of the group specificity, HLA-B17). Patients' DNA samples had been previously typed for HLA-B*57:01 with PCR-SSO or PCR-SSP and additional DNA sequencing (EPI Study). The results obtained by flow cytometry were compared with the results obtained by the DNA-PCR techniques. Results: By flow cytometry, 46 samples (7.97%) were positive for HLA-B17, 530 (91.86%) were negative, and 1 (0.17%) was undetermined. All samples found negative by flow cytometry were negative for HLA-B*57:01 by DNA-PCR. Of the HLA-B17 positive samples, 31 (67.4%) were positive for HLA-B*57:01, 2 (3.25%) were positive for HLA-B*57:03, 11 (26.1%) were positive for HLA-B*58, and 2 (3.25%) were negative for both HLA-B*57 and HLA-B*58 antigens. The undetermined sample was negative for HLA-B*57 and HLA-B*58 alleles by DNA-PCR. Conclusions: This study shows that flow cytometry with mAb3E12 is a highly sensitive method (no false negatives) to implement prior to DNA-PCR analysis for rapid screening of HLA-B*57:01. Additional confirmation by molecular HLA typing method would be required in less than 10% of the cohort of HIV-1-infected individuals.

In this paper a finite element formulation in terms of the magnetic field is presented for the analysis of waveguides with bianisotropic media. Such a formulation can deal with lossy inhomogeneous materials characterized by simultaneous permittivity, permeability, and cross-coupling (as in optical activity) arbitrary full tensors. The analysis takes into account arbitrary cross sections, and results in spurious-mode suppression, complex-mode computation, and the possibility of alternatively specifying the frequency or the complex propagation constant as an input parameter. In this way, many novel classes of waveguides with promising applications, such as chirowaveguides and chiroferrite-waveguides, can be analyzed. The formulation leads to a quadratic sparse eigenvalue problem which is transformed into a sparse generalized eigenvalue problem. This eigensystem is solved by the subspace method, the sparsity of the matrices being fully utilized. The proposed method has been validated by analyzing waveguides with biisotropic and bianisotropic materials. The agreement with previously published data is found to be excellent.

Background Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody. Several studies have proved its safety when used in different autoimmune chronic rheumatic diseases (ACRD). However, the real conditions of daily practice are not comparable to the ideal frame of a clinical trial. Objectives The aim of this study is to describe the profile of safety of RTX in patients with ACRD 12 and 24 months after the administration of the first cycle. Methods It is an observational retrospective study of patients diagnosed with ACRD who received treatment with RTX. Data were collected on demographic, clinical and biochemical profiles right before the first infusion, 12 and 24 months later. Other parameters were concomitant medication, prednisone dose, previous biologic treatment, accumulated RTX dose, infusion and anaphylactic reactions, infections, tumor relapses.Comparison was done using Wilcoxon non parametric test. Results Data were collected from 50 patients that received RTX. 24 months after treatment no major cytopenias or hypogammaglobulinemia were found. Hepatic and lipid profile did not show any alterations and complement levels did not experiment relevant changes. The average dose of prednisone was reduced significantly 1 year after the treatment. A decline in levels of acute phase reactants and antibodies was observed. This effect was maintained in every parameter with the exception of the rheumatoid factor; which continued presenting a downwards trend after 24 months. Concerning the infections, 3 patients were hospitalised (because of severe infections): two of them suffered from pneumonia and the other one required a surgical intervention in order to replace an infected prosthetic knee. 14 mild infections were registered: 8 mucocutaneous, 2 gastrointestinal, 2 respiratory and 2 genitourinary. There were no cases of primoinfection, reactivation of hepatic viruses or mycobacteria. No tumoral relapses, new diagnosis of tumors or demyelinising diseases were observed. 5 patients experimented mild infusion reactions but none of them had an anaphylactic reaction or died. Conclusions RTX has reduced the average maintenance dose of prednisone and also lowered the levels of serum immunoglobulins (including antibodies) without inducing hypogammaglobulinemia. It has proved to be a relatively safe treatment that does not cause hematic, hepatic toxicity or deep immunosuppresion after 12 and 24 months of follow up in patients with ACRD. Further studies are needed in order to evaluate long term safety of RTX. References Becerra E et al; Long-term Safety of Rituximab in Patients With Rheumatoid Arthritis. Int J Clin Rheumatol. 2012;7(4):383–390. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a debilitating disease and can affect both quality of life (QOL) and work productivity (WP) [1]. Ultrasound (US) is an important imaging technique increasingly used as a reliable tool in evaluating and monitoring RA patients [2]. US-detected subclinical synovitis (SS) has been detected in patients in clinical remission [3]. Objectives To investigate the relation between US-detected synovitis, clinically detected synovitis and US-detected SS and QOL and WP. Methods RA patients, aged between 18 and 59 years, with stable paid employment, were recruited. Clinical aseessment included 42 tender joint count (TJC) and 40 swollen joint count (SJC), Disease Activity Score (DAS) 28 and Health Assessment Questionnaire (HAQ). US assessment included 42 joints. At the joint level subclinical B mode synovitis (SSB) was defined as: absence of tenderness and swelling and presence of B mode score for synovitis ≥1 with or without power Doppler (PD) signal. Subclinical PD synovitis (PSS) was defined as absence of tenderness and swelling and presence of a PD score for synovitis ≥0. Global BM and PD scores for synovitis were assessed using the following scores: TS_B = total score of B-mode synovitis, TS_D = total score of PD synovitis, JS_B = count of joints with B-mode synovitis, JS_D =count of joints with PD synovitis, TSS_B = total score of SSB, TSS_D = total score of PSS, JSS_B = count of joints with SSB, JSS_D = count of joints with PSS. QOL [3] was described using 2 main domains: PCS (physical health) and MCS (mental health). WP was assessd using WPAI (work productivity and activity impairment) questionnaire [4]. Results 104 patients, with a mean age of 49±8 years and a mean disease duration of 141±103 months were included. At the assessment point, most of the patients had long-standing, low activity disease and a low functional impairment, as assessed by the DAS28-ESR and the HAQ, respectively. With the exception of TSS_B, most of the parameters that significantly correlated with QOL and WP were clinical variables. However, these correlations were weak (r ≤0,39), being the highest with TJC. Conclusions Neither clinical and US detected synovitis nor US detected SS showed a consistent relation with QOL and WP in our population of RA patients. TJC seems to be the clinical parameter that better correlates with QOL and WP. References Chorus AMJ, Miedema HS, Boonen A, van der Linden SJ. Quality of life and work in patients with rheumatoid arthritis and ankylosing spondylitis of working age. Ann Rheum Dis 2003;62:1178–1184 Micu MC, Fodor D. Concepts in monitoring the treatment in rheumatoid arthritis- the role of musculoskeletal ultrasound. Part I: synovitis. Med Ultrason. 2015 Sep;17(3):367–76. Gartner M, Alasti F, Supp G, Mandl P, Smolen JS, Aletaha D. Persistence of subclinical sonographic joint activity in rheumatoid arthritis in sustained clinical remission. Ann Rheum Dis. 2015 Nov;74(11):2050–3. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics 1993; 4(5):353–65 Disclosure of Interest None declared

Background B-cell depletion therapy decreases autoantibodies formation as rheumatoid factor and anti–citrullinated protein antibodies (ACPA). Other therapeutic targets (TT) such as anti-TNF (tumor necrosis factor), anti-IL-6R (interleukin-6 receptor) and anti-CTL4A (cytotoxic T-lymphocyte antigen-4) modulate the B-cells proliferation/maturation and indirectly the production of autoantibodies. ACPA titers provide us information about disease activity and may be critical for inducing clinical remission in rheumatoid arthritis (RA) patients. Objectives To evaluate the impact of the therapeutic targets: anti-TNF; anti-IL6R and anti-CTLA4 on ACPA titers in RA patients. Methods In this longitudinal study we selected ACPA positive patients naive to BT (N=27). All patients were assessed at baseline and after 4, 8, 12, 24 and 36 months (m) of treatment initiation. Disease activity was assessed by the 28 joint count-disease activity score (DAS28) according to C-Reactive Protein (CRP). ACPA isotypes (IgG, IgA and IgM) were determined by ELISA (CCP2-plates, Eurodiagnostica,SE). Anti-human antibodies isotype specific were used (Binding Site, UK). Statistical analysis was performed according to TT (anti-TNF, anti-IL6R and anti-CTLA4) and anti-TNF therapies (IFX, ADA, ETN). Results We found a significant DAS28-CRP decrease in: anti-IL6R (p=0.017, p=0.018, p=0.018, p=0.028, p=0.028) and anti-TNF (p=0.002, p=0.002, p=0.003, p=0.004, p=0.007) groups at 4, 8, 12, 24 and 36m. Evaluating the anti-TNF treatments, we found a significant decrease on DAS28 in ADL at 4 (p=0.046) and ETN groups at 4, 8, 12 and 24m of treatment (p=0.043, p=0.043, p=0.043, p=0.043). Comparing TT, the most outstanding reduction of DAS28 was found in anti-IL6R group compared to anti-CTLA4 group (p=0.017) at 8m, probably due to a greater reduction of CRP in anti-IL6R group (p=0.018). Regarding ACPA isotypes, we only found a significant decrease in IgA-ACPA titers in anti-IL6R group at 4, 8 and 12m of treatment (p=0.012, p=0.036, p=0.046). No changes were found neither in other TT nor in anti-TNF therapies. Comparing TT, we found lower IgG-ACPA titers in anti-CTLA4 group compared to anti-IL6-R group (50.25,98.2U/ml) at 4m. The highest IgG-ACPA titers were found in anti-IL6R (228.7 U/ml) than anti-TNF (53.7U/ml) and anti-CTLA4 groups (71.7U/ml) (p=0.048, p=0.024) at 24m. For IgM-ACPA, the lowest titers were found in anti-IL6R than anti-CTLA4 at 4 and 12m (4m: 2.988 y 3.093OD;12m: 3.004 y 3.116OD) (p=0.012, p=0.017, p=0.017). Conclusions Patients treated with anti-IL6R and anti-TNF had the most outstanding reduction of DAS28 at the first 8m of treatment. Regarding ACPA isotypes, IgM-ACPA levels were higher in anti-CTLA4 than anti-IL6R probably due to inhibition of B cells class-switching by anti-IL6R therapy. Those patients treated with anti-IL6R presented a progressive decrease of IgA-ACPA and total IgA, as well as, a higher IgG-ACPA titer at 24m. These results showed that both therapies modulate the B cell maturation/differentiation and ACPA production by different immune-regulation pathways, as well as, the cell-cell interaction process. Our data suggests that B-cells and ACPA isotypes monitoring may be useful to further understand their role in the RA pathogenesis and its association with clinical response to BT. Disclosure of Interest None declared

This paper presents a new finite element formulation for solving arbitrarily shaped waveguides including lossy inhomogeneous anisotropic media. The materials are characterized by simultaneous [/spl epsi/] and [/spl mu/] full tensors. Complex-mode computation, spurious-mode suppression and the possibility of specifying the frequency as an input parameter are also achieved. The formulation leads to a quadratic eigenvalue problem of dimension N which is transformed into an efficient 2N-dimensional generalized eigensystem with sparse complex matrices. This eigensystem is solved by the subspace method, taking full advantage of the sparsity of the matrices. Permittivity and permeability tensors with some null terms allow an additional reduction from the N-dimensional quadratic eigenvalue problem to a N-dimensional sparse complex generalized eigensystem. The proposed method has been validated by analyzing different lossy, inhomogeneous and anisotropic waveguides. Results show good agreement with previously published data. >

Background Psoriatic arthritis (PsA) is an inflammatory spondyloarthritis associated with psoriasis. Over the recent years the treatment of PsA has changed dramatically with the use of synthetic (s) disease modified anti-rheumatic drugs (DMARDs) as well as biologic (b) DMARDs, particularly tumor necrosis factor inhibitors. The goal of all these therapies is to achieve remission or minimal disease activity (MDA) [1]. Once remission is achieved and sustained the question is whether the treatment should be continued at full dosage, at a tapered dosage or should be discontinued. For PsA there are no recommendations for dosage tapering or discontinuation of biologic therapy and literature data regarding maintained clinical remission is conflicting. B-mode (BM) musculoskeletal (MS) ultrasound (US) has been widely shown to be more sensitive than clinical assessment in detecting joint synovitis and enthesitis [2,3] and Doppler technique is able to identify inflammatory activity [3,4]. Objectives To describe and compare clinical and MSUS features between PsA patients treated with full and tapered dosage of bDMARDs. The secondary objective was to compare clinical and MSUS features between PsA patients treated with bDMARDs with and without concomitant sDMARDs. Methods We evaluated 102 patients with PsA treated with bDMARDs. The bDMARD dosage tapering had been made in patients with a maintained remission or MDA according to their attending rheumatologist and with the patient acceptance. The bDMARDs tapering consisted of the followings: increase the interval between doses for subcutaneous bDMARDs or reduction of the dose for intravenous bDMARDs. The clinical evaluation consisted of a dermatologic and rheumatologic assessment of disease activity. The presence of BM and colour Doppler (CD) synovitis, tenosynovitis, enthesopathy and paratenonitis was investigated by a rheumatologist blinded to drug dosage, clinical assessments and laboratory results. Results Seventy four (72.5%) patients received full dosage of bDMARDs and 28 (27.5%) received tapered dosage. The duration with biologic therapy and with current biologic therapy were significantly higher in patients with tapered dosages (p=0.008 and p=0.001, respectively). We found no significant differences between clinical, laboratory and US variables, both for BM and CD between patients with full and tapered dosage and between patients with and without concomitant sDMARD. Conclusions Clinical assessment, MSUS variables, and MDA status are similar in patients receiving full and tapered dosage of bDMARDs. References Gossec L et al. Ann Rheum Dis. 2012 Jan;71(1):4-12 Balint PV et al. Ann Rheum Dis 2002;61:905-10 D9Agostino MA et al. Arthritis Rheum 2003;48:523-33 Naredo E et al. Arthritis Rheum 2008;58:2248-56 Disclosure of Interest None declared

Background A high prevalence of foot pain (70-90%) has been widely described in rheumatoid arthritis (RA) (1-4). Foot inflammation in RA usually starts in the metarsophalangeal (MTP) joints, extends to other joints with consequent pain, deformities and functional impairment (5, 6). The foot disorders and complaints it might have their origins in inflammatory disease activity or biomechanical abnormalities. Objectives The objective of this cross-sectional prospective study was to establish what extend foot complaints in RA patients in remission or low disease activity may originate in subclinical inflammatory disease activity as opposed to podiatric biomechanical abnormalities. Methods We recruited 136 patients with foot complaints. Sixty-two were bDMARD-treated RA patients presenting DAS-determined remission or low disease activity while the remaining 74 were gender matched controls without rheumatic or muskoskeletal disorders. In an effort to identify the root cause of pain, we subjected both groups to a comprehensive podiatric and biomechanical assessment followed by an ultrasound (US) scan. Results Most RA patients and controls were female (77.4% and 83.8%, respectively). There was no statistical difference in the proportion of obese subjects in either group (p=0.792). Inappropriate shoes were used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia, particularly heel pain, was more frequent in the control group, with associated talalgia and metatarsalgia being more prevalent in the RA group (p Conclusions RA foot pathologies often seem to be linked to disease activity and ultrasound can be useful to help the clinician differentiate disease-related foot pain from other possible biomechanical causes. References Hooper L, et al. Arthritis Care Res.2012;64(8):1116-24. Rome K, et al. J Foot Ankle Res.2009;2:16. Rao S, Best Pract Res Clin Rheumatol 2012;26(3):345-68. Fuchs HA, et al. Arthritis Rheumatol.1989;32(5):531-7. van der Leeden M, et al. Rheumatology.2006;45(4):465-9. van der Leeden M, et al. Arthritis Res Ther.2010;12(1):R3. Disclosure of Interest None declared

Background Several studies have shown the relationship between anti-SSA-Ro/SSB-La antibodies and Systemic Lupus Erythematosus (SLE), Sjogren Syndrome (SS) and other autoimmune diseases in adult population. However, the expression of these autoantibodies and clinical correlation in juvenile patients is poorly described. Objectives To characterize the clinical and serological profile and primary rheumatic diseases in pediatric patients with positive anti-SSA-Ro and/or anti-SSB-La antibodies. Methods The data was obtained from a long term prospective cohort of patients under age 18 diagnosed with rheumatic diseases in a tertiary hospital in Spain. Demographic, clinical, and laboratory data were collected from 1986 to 2010. Patients were divided into 2 groups: anti-SSA-Ro/SSB-La positive and anti-SSA-Ro/SSB-La negative. Results A total of 187 patients were tested for anti Extractable Nuclear Antigens (ENA), with a following mean time of 11 years. Mean age at disease onset was 12.6 years and 77% were female. Fifty-four (28.9%) anti-SSA-Ro/SSB-La positive subjects were compared against 133 (71.1%) anti-SSA-Ro/SSB-La negative subjects. Among positive cases, 13 (24.1%) patients were double-positive for anti-SSA-Ro and anti-SSB-La, 51 (94.4%) were positive for anti-SSA-Ro and 3 (5.5%) were single-positive for anti-SSB-La. The anti-SSA-Ro/SSB-La antibodies were found less frequently (p=0.003) in the overlapping syndromes, and more frequently in SLE (p=0.007). In addition rheumatoid factor (p Conclusions Similarly to adults, we observed a relationship between anti-SSA-Ro/SSB-La antibodies and SLE in pediatric patients. However a low proportion of childhood primary SS exists in our anti-SSA-Ro/SSB-La positive cases. This could be explained by underdiagnoses related to the atypical clinical presentation of SS in pediatric population. Single-positive anti-SSB-La patients are uncommon, the clinical significance of this serological result remains uncertain in children. References Rheumatol Int (2014) 34:1123–1127. Disclosure of Interest None declared

In this paper, an efficient finite-clement formulation is presented for the analysis of the propagation characteristics in arbitrarily shaped lossy inhomogeneous waveguides loaded with chiral media. It is a simplified form of the one proposed for the bi-anisotropic media. In this formulation, showing no spurious modes, the frequency or the propagation constants may be treated as eigenvalues of a resulting sparse quadratic eigenproblem. However, in order to handle losses easily and to facilitate computation of complex modes, the frequency is specified as an input parameter and the eigensystem is solved for the complex propagation constant as the eigenvalue. This sparse eigensystem is further transformed into a generalized one, thus maintaining the sparse properties of the matrices. New numerical finite-element results are presented.

The human immunodeficiency virus-1 (HIV-1) preferentially infects CD4+ cells, leading to their destruction. In contrast to other viral infections, the immune system is unable to keep the HIV infection under permanent control in most cases. This failure ultimatively results in immunodeficiency with occurrence of AIDS-defining diseases. In recent years, highly active antiretroviral therapy (HAART) has become available, and the number of AIDS cases and deaths have decreased dramatically. However, limitations of HAART become more apparent, demanding greater emphasis on search for alternative approaches. Stimulation and modulation of the immune response to HIV are new and promising strategies. A prerequisite, however, is the knowledge about immunologic defense mechanisms against HIV. In this article, the major factors of innate and acquired immune responses to HIV are described.

A generalized scattering matrix of a circular waveguide with several posts inserted has been derived. The number of posts can be selected from one to eight and placed at 45° angles on the waveguide perimeter. Computation is based on an automated finite-element-mode-matching method that only requires the main geometrical dimensions as input data. A structure containing three screws inserted in a dualmode cylindrical cavity, iris coupled to input and output rectangular waveguides, has been analyzed. Excellent agreement with measured data has been found. © 1994 John Wiley & Sons, Inc.