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Psoriatic arthritis (PsA) is a chronic, progressive disease that places a significant burden on patients and healthcare systems. The SUSTAIN study collected real-world evidence on long-term effectiveness, impact on quality of life, and safety of ustekinumab treatment for PsA.SUSTAIN was a prospective, non-interventional study conducted in Germany. Patients with active PsA received ustekinumab for 160 weeks in routine clinical care, with assessments at baseline, week 4, and every 12 weeks thereafter. This analysis focuses on patients who remained in SUSTAIN until week 160.Of 337 patients enrolled, 129 were documented at week 160, of which 123 (95.3%) had received previous PsA medication, including biologics. Decreases from baseline to week 4 were observed for tender joint count (TJC, 8.0 to 5.8) and swollen joint count (SJC, 4.5 to 3.1); these decreases continued to week 28 and were maintained to week 160 (1.0 and 0.4, respectively). Similarly, skin assessments in patients with PsA and psoriasis revealed improvement at week 4, which continued to week 28, with a sustained effect until week 160. Similar patterns of response were observed for patient-assessed pain, sleep quality, and health scores. Improvements in TJC, SJC, Psoriasis Area and Severity Index, and affected body surface area were observed irrespective of the number of prior biologic therapies used. Minimal disease activity was achieved by 36 (31.9%) patients at week 28, and by 38 (33.6%) at week 52. Ustekinumab-related adverse events (AEs) and serious AEs were reported in 61 (47.3%) and 4 (3.1%) patients, respectively. At week 160, 100% of patients assessed ustekinumab tolerability as good or very good.In a real-world setting, patients with active PsA who received ustekinumab until 160 weeks (3 years), including those who received prior biologic therapies, had a rapid onset of effect and sustained response to treatment, with high tolerability.PEI NIS No. 290.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.

Summary Background Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. Methods The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5–15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints–erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4–6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov , NCT02573012 . Findings Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35–0·73) with tapered prednisone and −0·08 (–0·27 to 0·12) with continued prednisone (difference 0·61 [0·35–0·88]; p Interpretation In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Funding F Hoffmann-La Roche.

Research indicates that rheumatic disorders are accompanied by decreased chemosensory function. The present study aimed to specifically evaluate this issue in patients with rheumatoid arthritis (RA). 212 RA patients (43 men, 169 women, mean age 59 ± 13.3 years), and 30 healthy controls (10 men, 20 women, mean age 40 ± 15.3 years), were included in this study. Chemosensory measurements consisted of olfactory testing using the “Sniffin’ Sticks” test battery (with odor thresholds, odor discrimination and odor identification; OT, OD, OI) and gustatory testing on a suprathreshold and a quasi-threshold level using “taste sprays” and “taste strips”, respectively. In addition, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and RA autoantibodies (anti-cyclic citrullinated peptides, RA factors) were evaluated. Olfactory measurements showed 4% of the RA patients functionally anosmic and 40% hyposmic. RA patients scored significantly lower in suprathreshold olfactory tests (OD, OI) compared to controls (OI: 12.5 ± 2.5 vs. 14.1 ± 1.3; OD: 11.3 ± 2.7 vs. 12.9 ± 1.7). In addition, RA patient had decreased taste function compared to healthy individuals (10.4 ± 2.6 vs. 11.7 ± 1.7). Chemosensory function did not correlate with parameters related to the severity of disease. Chemosensory function (taste, OD and OI) appears to be decreased in RA patients. In contrast, OT was not affected. Changes in chemosensory function seem to be independent of disease parameters such as duration of disease or disease activity.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.Bei einer systemischen Erkrankung ist systemisches Denken erforderlich. In diesem Leitbild definieren wir Rheumatologie, beschreiben die Rolle der Deutschen Gesellschaft für Rheumatologie und umschreiben den rheumatologischen „Geist“, der uns für und in unserem Fach antreibt. Rheumatologen widmen sich der Verbesserung der Lebensqualität ihrer Patienten im akuten, chronischen und Rehabilitationsstadium auf Basis der aktuellen Datenlage und einer tragfähigen Arzt-Patienten-Beziehung. Wir denken, handeln und interagieren systemisch, wissenschaftlich, konsequent, transparent, verlässlich, integrativ, innovativ und begeistert.

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

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

Research indicates that rheumatic disorders are accompanied by decreased chemosensory function. The present study aimed to specifically evaluate this issue in patients with rheumatoid arthritis (RA).212 RA patients (43 men, 169 women, mean age 59 ± 13.3 years), and 30 healthy controls (10 men, 20 women, mean age 40 ± 15.3 years), were included in this study. Chemosensory measurements consisted of olfactory testing using the "Sniffin' Sticks" test battery (with odor thresholds, odor discrimination and odor identification; OT, OD, OI) and gustatory testing on a suprathreshold and a quasi-threshold level using "taste sprays" and "taste strips", respectively. In addition, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and RA autoantibodies (anti-cyclic citrullinated peptides, RA factors) were evaluated.Olfactory measurements showed 4% of the RA patients functionally anosmic and 40% hyposmic. RA patients scored significantly lower in suprathreshold olfactory tests (OD, OI) compared to controls (OI: 12.5 ± 2.5 vs. 14.1 ± 1.3; OD: 11.3 ± 2.7 vs. 12.9 ± 1.7). In addition, RA patient had decreased taste function compared to healthy individuals (10.4 ± 2.6 vs. 11.7 ± 1.7). Chemosensory function did not correlate with parameters related to the severity of disease.Chemosensory function (taste, OD and OI) appears to be decreased in RA patients. In contrast, OT was not affected. Changes in chemosensory function seem to be independent of disease parameters such as duration of disease or disease activity.

Background The detection of joint swelling caused by synovitis is important for the diagnosis of inflammatory arthritis. Ultrasound (US) and MRI have proven to be more sensitive and reliable than physical examination, but they are time-consuming and expensive. The automated breast volume scanner was developed to acquire serial B-mode pictures of the female breast and these can be analyzed in all three dimensions. Objectives To analyze the value of automated B-mode ultrasound employing the ABVS system in detecting synovitis of the finger joints compared to manual ultrasound (mUS) and physical examination, using MRI as the gold standard. Methods 19 consecutive patients suffering from active rheumatoid (n=15) or psoriatic (n=4) arthritis were included. Automated and mUS were conducted with a linear array (ACUSON S2000™, 11 MHz). Multiplanar reconstruction enabled examination of the images for the presence of synovitis. Results 90% of the hand joints were assessable by automated ultrasound. Automated US detected 12.0, mUS 14.2, MRI 13.4, and clinical examination 4.1 positive joints – i. e. joints with synovitis - on average per patient. The inter-observer reliability of both assessors for automated and mUS, MRI, and physical examination, was 66.9%, 72.7%, 95.1%, and 88.9%, respectively. 84.3% of the joints classified as positive on MRI were confirmed by automated ultrasound, 85.5% on mUS, and 36.0 on physical examination. This translated into a sensitivity of 83.5%, 85.5%, and 36.0% for the three methods, respectively. Conclusion: Automated ultrasound is a promising ultrasound method for assessing small joints in patients with inflammatory arthritis.

Background:Inflammatory rheumatic disorders are very complex and require high medical resources. However, there is a shortage of care for these patients, which results in suboptimal reach of therapy objectives. Nevertheless, these very objectives need to be pursued quickly to prevent permanent joint damage. In order to ensure adequate care, multidisciplinary teams which include clinical nurse specialists are required. These clinical nurse specialists play an important role in improving standard-of-care in addition to the rheumatologist. The current standard of care ensures that essential medical provision remains intact, however, psychological, social, rehabilitative and educational needs are often skipped due to time constraints. While studies from e.g. the UK and Denmark have already supported the non-inferiority of nurse-led care (NLC)1, no such studies have yet been published in Germany.Objectives:To demonstrate the non-inferiority of NLC to the current standard-of-care, rheumatologist-led care (RLC), for patients with seropositive rheumatoid arthritis (RA) with induction, escalation or change of therapy regarding disease activity as well as different patient reported outcomes (PROs).Methods:This trial was conducted as a prospective multi-centered RCT with a non-inferiority design over the course of 12 months. Based on power calculations, 236 adults with RA were included in the study and randomized to either NLC or RLC. The primary outcome measure is disease activity (DAS28), assessed at baseline (T0), 6 weeks (T1), 3,6, 9, and 12 months (T3, T6, T9, T12). Secondary measures are health related quality of life (RAID), functionality (FFbH) and depression (PHQ9).Results:There are no significant differences between intervention group (IG) (n=117) and control group (CG) (n=119) at baseline. The mean age of the IG is 58.80 years (SD=12.09) and of the CG 58.34 years (SD=11.72). 72.4% of the IG and 78.1% of the CG are female. The mean duration of symptoms was 147 months (SD=144.63) for the IG and 116 months (108.89) for the CG. The mean DAS28 for the IG is 4.36 (SD=1.24) and 4.51 (SD=1.24) for the CG.A mixed one-way repeated measures ANOVA showed that the DAS28 improves significantly over time, Huyn-FeldtF(4.42, 751.72) = 105.701,p< .001, partialη2= 0.383, but the interaction of the DAS28 and the randomization is not significant, Huyn-FeldtF(4.42, 751.72) = 1.464,p= 0.260, partialη2= 0.009. No main effect for randomization was found, meaning that the IG and CG did not differ significantly,F(1, 170) = 1.005,p= 0.317, partialη2= 0.006.The Mann-Whitney-Test showed that the change of the secondary outcomes does not depend on the randomization FFbHU= 4978.50,Z= -.755,p=.450. RAIDU= 5121.00,Z= -.539,p=.590. PHQ9U= 4800.50,Z= -1.281,p=.200. The secondary outcomes improve significantly over time, as shown by a Wilcoxon Signed Rank test for the FFbHZ= -5.589,p< .001, the RAIdZ= -9.884,p< .001 and the PHQ9Z= -7.960,p< .001.Conclusion:The results support the non-inferiority of NLC in the management of RA regarding the primary and secondary outcome measures and provide first evidence that NLC could improve care and help carry the doctors’ workflow.Figure 1.Figure 2.References:[1]de Thurah A, Esbensen BA, Roelsgaard IK, et al. Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis: a systematic review and meta-analysis. RMD Open 2017;3:e000481.Disclosure of Interests:Juliana R Hoeper: None declared, Georg Gauler Consultant of: Abbvie, Lilly, MSD, Speakers bureau: Abbvie, Celgene, Novartis, Sanofi,, Dirk Meyer-Olson Grant/research support from: Novartis, Sandoz Hexal, Consultant of: Abbvie, Amgen, Bristol Myers Squibb, Chugai, Lilly, Mylan, Novartis, Sandoz Hexal, Sanofi, Speakers bureau: Abbvie, Bristol Myers Squibb, Chugai, Lilly, Novartis, Pfizer, Sandoz Hexal, Sanofi, Karin Rockwitz Consultant of: Janssen Cilag, Speakers bureau: Janssen Cilag, Patricia Steffens-Korbanka Consultant of: Abbvie, Chugai, Novartis, Sanofi, Mylan, Lilly, Speakers bureau: Abbvie, Chugai, Novartis, Sanofi, Lilly, Carsten Stille: None declared, Jochen Walter Consultant of: Pfizer, Speakers bureau: AbbVie, Frauenhofer Institut, Gilead, Janssen-Cilag, Medac, Novartis, Pfizer, Martin Welcker Grant/research support from: Abbvie, Novartis, UCB, Hexal, BMS, Lilly, Roche, Celgene, Sanofi, Consultant of: Abbvie, Actelion, Aescu, Amgen, Celgene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Speakers bureau: Abbvie, Aescu, Amgen, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB, Joerg Wendler Consultant of: Janssen, AbbVie, Sanofi, Speakers bureau: Roche, Chugai, Janssen, AbbVie, Novartis, Jan Zeidler: None declared, Kirsten Hoeper Consultant of: AbbVie, Celgene,, Speakers bureau: Abbvie, Chugai, Novartis, Lilly, Celgene, Sandoz Hexal

ObjectiveTo determine the non-inferiority of nurse-led care (NLC) in patients with anticitrullinated protein antibody (ACPA)-positive and/or rheumatoid factor (RF)-positive rheumatoid arthritis (RA) with active disease who are starting disease-modifying antirheumatic drug therapy, following treat-to-target (T2T) recommendations.MethodsA multicentre, pragmatic randomised controlled trial was conducted to assess clinical effectiveness, anxiety, depression and patient satisfaction following a non-inferiority design. The participants were 224 adults with ACPA/RF-positive RA who were randomly assigned to either NLC or rheumatologist-led care (RLC). The primary outcome was the Disease Activity Score in 28 Joints measured with C reactive protein (DAS28-CRP) assessed at baseline and after 3, 6, 9 and 12 months. A DAS28-CRP difference of 0.6 was set as the non-inferiority margin. Mean differences between the groups were assessed following per-protocol and intention-to-treat strategies.ResultsDemographic data and baseline characteristics of patients in the NLC group (n=111) were comparable to those of patients in the RLC group (n=113). The improvement in disease activity (change in DAS28-CRP, primary outcome) over the course of 12 months was significant in both groups (pConclusionThis study supported the non-inferiority of NLC in managing T2T and follow-up care of patients with RA with moderate to high disease activity and poor prognostic factors in addition to RLC.Trial registration numberDRKS00013055.

Background:Blended learning is an increasingly popular learning supplement for traditional classroom-based courses in medical education. Once implemented, many factors influence its success. This was demonstrated by Shivetts et al., who concluded that student motivation plays a major role. In particular, if a learner is not self-motivated, e-learning may not represent the best learning environment.1However, gamification methods are known to enhance motivation in medical education and, if used correctly, can overcome this deficit.2For this purpose, a quiz duel was created and used as a blended learning approach for health professional training in rheumatology. We hypothesize that the use of the quiz duel gamification technique improves learners’ motivation to successfully complete their blended learning course.Objectives:To investigate the potential of gamification methods in motivating health professionals to answer multiple choice questions (MCQs) in a pilot blended learning scenario.Methods:Four hundred and sixty MCQs were developed in accordance with the learning objectives of a certified training course and integrated into a learning management system (LMS). As a gamification technique, a duel mode was created. Course participants had access via an individual user account and used personal smartphones. After each answer was provided, the learners received corrective and explanatory feedback, as well as information on how the duel opponent answered. Incorrectly answered MCQs were repeated in further duels.Information on the number of MCQs answered (1), days learned (2), and learning time spent (3) was collected and analyzed. Each day on which at least one MCQ was answered counted as a learning day per user. The learning time was calculated with 1.5 min per MCQ answered. Analysis was performed over a 15-week period (08/19–12/19).The training event (“RFAplus”) was organized by the Rheumatologische Fortbildungsakademie GmbH and took place on three weekends in intervals of four weeks in Germany. The LMS used was Humeo (Humeo GmbH). All users agreed to the terms and conditions of use and data protection before participating in the blended learning intervention.Results:Nineteen female health professionals in rheumatology participated in the study. The mean age of participants was 43.5 years (range, 21–60 years). The 460 MCQs were answered 20,397 times, with 1039 MCQs per user (range, 247-1839 MCQs) during the 15-week period (105 days). Each MCQ was answered 2.33 times. In total, there were 1167 learning days, with 60.8 days per user (range, 15-95 days). The users spent 30,596 min (509.9 h) answering the MCQs, resulting in 1,610 min (or 26.8 h) per user. Furthermore, each user answered 17.5 MCQs and spent an average of 26 min per learning day.Conclusion:Blended learning is an interactive method to potentially extend learning time over several weeks. However, the success of this technique lies in motivating the participants to continue learning after the event. A quiz duel as a gamification technique proved to be effective in motivating participants to learn daily. In our study, learners spent an average of 27 h, i.e., almost half of the total attendance time of 60 h, learning. Correspondingly, this technique could also replace parts of lengthy face-to-face courses in an attempt to save costs in the future. Information drawn from the MCQs could potentially serve as promising learning analytics.References:[1]Shivetts, C. E-Learning and Blended Learning: The Importance of the Learner A Research Literature Review.Int. J. E-Learn.10, 331–337 (2011).[2]Pesare, E., Roselli, T., Corriero, N. & Rossano, V. Game-based learning and Gamification to promote engagement and motivation in medical learning contexts.Smart Learn. Environ.3, 5 (2016).Disclosure of Interests:Ruben Sengewein: None declared, Patricia Steffens-Korbanka Consultant of: Abbvie, Chugai, Novartis, Sanofi, Mylan, Lilly, Speakers bureau: Abbvie, Chugai, Novartis, Sanofi, Lilly, Joerg Wendler Consultant of: Janssen, AbbVie, Sanofi, Speakers bureau: Roche, Chugai, Janssen, AbbVie, Novartis, Max Kieslich: None declared, Erik Schmok: None declared, Georg Gauler Consultant of: Abbvie, Lilly, MSD, Speakers bureau: Abbvie, Celgene, Novartis, Sanofi

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

Background Tumor necrosis factor inhibitors (TNFi) are the most frequently used bDMARDs in RA patients. TNFi induces remission in a substantial numbers of patients. Once remission, particularly sustained remission is achieved the question arises whether TNFi can be successfully tapered. To date biomarkers, which can help to predict if TNFi can be tapered or stopped, remain to be developed. Objectives To test whether residual subclinical inflammation assessed by multi-biomarker disease activity (MBDA) predicts the risk of disease relapse after tapering or stopping TNFi treatment in RA patients in sustained remission. Methods Sub-analysis of TNFi treated patients of the RETRO study, a randomized-controlled study in RA patients in sustained (>6 month) DAS28 remission comparing 3 different DMARD treatment strategies (continuation of full dose, 50% dose tapering, stopping after 50% dose tapering). Patients were followed over one year for the occurrence of relapses as defined by leaving DAS28-ESR remission (>2.6 units) (1). Vectra-DA tests were done in the baseline samples of all patients included into the RETRO study. MBDA score was calculated according to previously defined algorithms with low MDBA score defined as Results Of the 151 patients included in the RETRO study, 42 received TNFi treatment (mean age: 56 ys, 25 (60%) females, 78% concomitant csDMARDs; 69% ACPA/RF positive. Baseline demographic and disease specific characteristics of these patients were comparable to the non-TNFi treated patients of the RETRO study. 26/42 patients (62%) had low MBDA scores at baseline, while 16/42 (38%) had moderate/high scores. Relapse rates were significantly (chi square p=0.016) lower in RA patients with low MBDA scores (N=8 of 26; 31%) than in those with moderate/high scores (N=11 of 16; 69%) (Figure; left graph). When separately analyzing only patients tapering TNFi (N=29), relapse rates were moderate in RA patients with low MBDA scores (N=6 of 16; 37%) but high in those with moderate/high scores (N=10 of 13; 77%) (chi square p=0.015) (Figure; right graph). Conclusions These data show that the majority of RA patients in sustained clinical remission with low MBDA scores can successfully taper TNFi. In contrast tapering cannot be recommended in patients with moderate to high MBDA scores, as relapse rates are high in these patients. References Haschka J et al. Ann Rheum Dis 2016,75;45–51. Curtis JR et al. Arthritis Care Res 2012;64:1794–803. Disclosure of Interest None declared

Background Achieving remission is the ultimate treatment goal in patients with rheumatoid arthritis (RA). With the development and wider use of highly effective disease modifying anti-rheumatic drugs (DMARD) about half of RA patients reach the disease remission state (1), raising the question about tapering or stopping anti-rheumatic treatment and appropriate predictors (2). Objectives To analyse the effect of a risk-stratified DMARD tapering algorithm based on multiple-biomarker disease activity (MBDA) score and anti-citrullinated protein (ACPA) status for successful DMARD tapering and treatment cost reduction in RA patients in sustained remission enrolled in the prospective randomized controlled RETRO study (3,4). Methods MBDA scores and ACPA status were determined in the baseline samples of 146 patients in sustained remission. Patients either continued DMARDs (arm1), tapered dose by 50% (arm 2) or stopped DMARDs after tapering (arm 3) for one year according to the RETRO study protocol. Direct treatment costs (including testing costs at baseline) were evaluated every three months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates. Results RA patients with a low MBDA score ( Conclusions Combining MBDA score and ACPA status allows risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD. Given that previous data of the RETRO have shown that patients relapsing after tapering their DMARDs respond well to their reintroduction, a stratified tapering and stopping of DMARDs is not only a cost economic but also clinically feasible strategy. References Aga AB et al. Ann Rheum Dis. 2013;74:381–8. Schett G et al. Ann Rheum Dis. 2016 Aug;75(8):1428–373. Haschka J et al, Ann Rheum Dis. 2016;75:45–51. Rech J et al, Ann Rheum Dis. 2015; Oct. 19. Disclosure of Interest None declared

ObjectivesTo investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease.MethodsIn this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation.ResultsIn 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age 2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy.ConclusionsMild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms.Clinical trial registration numberThis study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483).

Self-reports of fibromyalgia (FM) patients about an enhanced olfactory acuity have been used to characterize them as persons with a general increased sensitivity to sensory input consistent with a central sensitization. However, as reduced activations in some brain areas also seem to accompany FM, a multisensory hypersensitivity is not a necessary consequence.FM patients meeting ARA (American Rheumatism Association) criteria (16 women and one man, aged 23-56 years, spontaneous pain 32-91 mm visual analog scale [VAS], 14-18 tender points with a pressure pain threshold of 1.5±0.7 kg/cm(2)) received an olfactory test (Sniffn' Sticks) to assess their odor thresholds to n-butanol and their ability to discriminate and identify odors. Healthy controls were 14 age-matched women and one man.Patients had poorer odor identification than controls (14.6±1.3 vs. 15.5±0.6; p0.05) but did not differ in odor thresholds or odor discrimination. This test result contrasted with the patients' self-ratings of their olfactory sensitivity as higher than average.The perception of FM patients as being multisensory hypersensitive is not supported by present results. In contrast to the subjects' self-ratings, measurements of olfactory function showed a slightly reduced odor identification, with a by-and-large normal performance.

Objective Single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor gene TNF at positions −238 and −308 have been associated with psoriasis vulgaris and psoriatic arthritis (PsA). The strong linkage disequilibrium (LD) at chromosome region 6p21, a region known to harbor risk factors for psoriasis susceptibility (PSORS1) other than just SNPs of the TNF gene, renders the interpretation of these findings difficult. The aim of this study was to analyze several SNPs of the TNF gene and its neighboring LTA gene for independent and dependent carriage of the PSORS1 risk allele. Methods SNPs in the promoter of the TNF (−238G/A, −308G/A, −857C/T, and −1031T/C), LTA (+252A/G), TNLFRSF1A (+36A/G), and TNLFRSF1B (+676T/G) genes were genotyped in 375 psoriasis patients, 375 PsA patients, and 376 controls. The Trp- Trp-Cys-Cys haplotype of the CCHCR1 gene (CCHCR1*WWCC) was used as an estimate of the risk allele PSORS1. Results Whereas we were able to confirm the previously described strong association of allele TNF*-238A with psoriasis, our study revealed that this association was completely dependent on carriage of the PSORS1 risk allele. For PsA, but not psoriasis vulgaris without joint involvement, a strong association with the allele TNF*-857T (odds ratio 1.956 [95% confidence interval 1.334–2.881]; corrected P = 0.0025) was also detected in patients negative for the PSORS1 risk allele. Conclusion Our results indicate that there are genetic differences between psoriasis vulgaris patients with and without joint manifestations. While the previously reported association between TNF*-238A and psoriasis seems to primarily reflect LD with PSORS1, TNF*-857T may represent a risk factor for PsA that is independent of the PSORS1 allele.

Objectives: To investigate remission rates in rheumatoid arthritis patients exposed to tocilizumab treatment in real life clinical practice and to test whether concomitant conventional and previous biological disease modifying anti-rheumatic drugs treatment affects the efficacy of tocilizumab to reach remission. Methods: Between January 2009 and December 2012 disease activity was analyzed in 272 rheumatoid arthritis patients exposed to tocilizumab at the onset of treatment and sequentially thereafter, i.e. every four weeks at the time of infusion. Aside from demographic and disease-specific variables, previous and concomitant conventional and biologic disease modifying anti-rheumatic drugs therapy was documented in all patients. Multivariate logistic regression analyses were conducted to identify factors influencing Disease Activity Score 28 remission and attrition to tocilizumab treatment. Results: 219 (80.5%) of all patients were female. Mean Age was 55.48 ± 13.23 years and our patients had mean disease duration of 12.48 ± 9.30 years. Disease Activity Score 28 significantly decreased from 5.00 ± 1.52 at baseline to 3.09 ± 1.49 at the latest infusion. Mean treatment period was 58.28 ± 43.95 weeks. A total of 101 patients (42.8%) achieved Disease Activity Score 28 remission, which was significantly associated to the length of tocilizumab exposure. Achievement of Disease Activity Score 28 remission was independent from the concomitant use of conventional disease modifying anti-rheumatic drugs. Previous exposure to tumour necrosis factor inhibitors but not rituximab significantly reduced the likelihood to achieve Disease Activity Score 28 remission. Two logistic regression analyses revealed baseline disease activity and duration of tocilizumab therapy as independent factors for Disease Activity Score 28 remission, whereas age and concomitant methotrexate therapy were linked to attrition to tocilizumab treatment. Conclusion: Remission rates found in this observational study are comparable to those of randomized controlled trials and those of big post-marketing surveillance studies. Remission rates of rheumatoid arthritis patients treated with tocilizumab in clinical practice are not influenced by concomitant disease modifying anti-rheumatic drugs use. Previous exposure to tumour necrosis factor inhibitors but not to rituximab decreases the chance to reach remission with tocilizumab.

Objective To examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, or radiographic progression in, rheumatoid arthritis (RA). Methods The contribution of 2 SNPs (I50V and Q551R) in the coding region of IL4R to RA susceptibility was analyzed by allele-specific polymerase chain reaction in a case–control study of 471 RA patients and 371 healthy controls. Patients with available radiographs of the hands and feet obtained 2 years after disease onset (n = 302) were stratified retrospectively according to radiologic outcome into an erosive and a nonerosive group to evaluate the association between IL4R SNPs and disease progression. Results No differences in the genotype and allele frequencies of the I50V or Q551R SNPs were identified between the RA patients and healthy controls. In contrast, significant differences in the distribution of I50V IL4R SNP genotypes between patients with erosive and nonerosive disease were observed (χ2 = 15.68, P = 0.0004). Bone erosions at 2 years after disease onset were present in 68.1% of patients homozygous for the V50 allele compared with 37.0% of patients homozygous for the I50 allele (odds ratio 3.86, P < 0.0001). This association was independent of individual factors previously associated with severe disease, such as rheumatoid factor or the HLA–DR shared epitope. On a cellular level, the V50 allele conferred significantly reduced responsiveness to interleukin-4, providing a possible mechanism for the association of the I50V IL4R polymorphism with early erosions in RA. Conclusion Our data identify the I50V IL4R SNP as a novel genetic marker in RA, showing high predictive value for early joint destruction.

To determine whether the three common independent sequence variants of the putative pleiotropic non-MHC autoimmune gene CARD15 influence disease susceptibility in large German cohorts of patients with psoriatic arthritis and psoriasis vulgaris, before and after stratification to HLA-C.DNA was obtained from 375 patients with psoriatic arthritis, 281 patients with psoriasis vulgaris without joint involvement, and 376 controls. The three variants of the CARD15 gene (R702W, G908R, leu1007fsinsC), and two single nucleotide polymorphisms of the HCR gene (HCR-325, HCR-2327) for HLA-C stratification were genotyped using allelic discrimination Taqman assays.No significant differences in genotype frequencies were observed between controls and either the psoriatic arthritis or the psoriasis vulgaris patient population, even after stratification to HLA-C in both patient cohorts, or to the type of joint involvement within the psoriatic arthritis group.The lack of genetic association between the most common Crohn's disease alleles of the CARD15 gene and psoriatic joint disease on large cohorts of white patients does not support a recently claimed role for CARD15 as the first non-MHC susceptibility gene in the pathogenesis of psoriatic arthritis, but confirms and extends previous studies in the case of psoriasis vulgaris.

A DNA variant, rs734232, altering a RUNX1 binding site was recently reported as susceptibility allele at PSORS2 (17q25) in cohorts of psoriasis patients from the US. A testing of this variant in psoriasis patients from Germany did not confirm this association in 300 trios nor in two case-control studies with 281 patients with psoriasis vulgaris and 375 patients with psoriatic arthritis, respectively. These results fail to support rs734232 as a psoriasis susceptibility factor in German psoriasis patients.

Pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) is unresolved. Dysregulation of programmed cell death is discussed as a pathogenetic factor. We have previously shown that increased in vitro apoptosis of cultured peripheral blood mononuclear cells (PBMC) is nonspecific for SLE. Importantly, however, in recent experiments with SLE PBMC from patients with infections and fever in vitro apoptosis was strongly accelerated. We therefore hypothesized that regulation of apoptosis might be disturbed in activated SLE lymphocytes. Thus, we generated phytohemagglutinine (PHA)/IL-2 stimulated lymphoblasts in vitro. These lymphoblasts readily undergo apoptosis after culture in cytokine-free medium, and can be rescued by addition of gammac-chain cytokines IL-2, -4, -7, or -15. In lymphoblasts from 60 SLE patients tested in comparison to lymphoblasts from normal donors cultured in parallel, we found significant hyporesponsiveness to gammac-chain cytokines in SLE cells. Minor differences were also seen in lymphoblasts from patients with other systemic autoimmunopathies (mixed connective tissue disease, vasculitis, n=49)and in lymphoblasts from patients with other autoimmune diseases (mainly rheumatoid or reactive arthritis, myositis, n=44). In patients with high erythrocyte sedimentation rate (> 25 mm/h), TNF-alpha (> 6.5 pg/ml) or IL-12 (> 4.7 pg/ml) serum levels or detectable IFN-gamma concentrations hyporesponsiveness to gammac-chain cytokines was even more pronounced in SLE lymphoblasts, but not in lymphoblasts from the other groups. Moreover, increased apoptosis was seen in lymphoblasts from SLE patients with decreased complement (C)4 or elevated dsDNA antibody levels. In conclusion, these data suggest that in SLE patients with increased inflammatory activity and/or Th1 dominance signaling through gammac-chain cytokine receptors is deteriorated, leading to facilitated apoptosis of activated lymphocytes and enlarged onflow of apoptotic material.

The aim of the study was to investigate whether there are changes of the nociceptive system in patients with chronic inflammatory joint pain. A pain model was used which is based on the recording of cortical chemo-somatosensory event-related potentials (CSSERP) after nociceptive stimulation of the nasal mucosa with gaseous carbon dioxide (CO(2)). Twenty-five patients with rheumatoid arthritis (RA) were compared to healthy controls matched for age and gender. Responses to both different intensities of painful stimuli and constant intensities of series of 4 stimuli were analysed. When testing increasing CO(2) concentrations ratings and CSSERP amplitudes increased for both patients and controls. However, when repetitive stimulation was performed with an interval of 2s CSSERP amplitudes N1 were significantly greater in RA patients. It is hypothesized that chronic inflammatory joint pain changes nociceptive processing in terms of generalized changes of the nociceptive system which may amplify chronic pain.

Introduction Psoriasis susceptibility locus 4 (PSORS4) is a susceptibility locus for psoriasis vulgaris (PsV), a common inflammatory, hyperproliferative skin disorder. Recently, a deletion of 2 late cornified envelope ( LCE ) genes within epidermal differentiation complex on chromosome 1 was shown to be enriched in 1426 patients with PsV, suggesting compromised barrier function in deletion carriers. This genetic association was subsequently confirmed in a German cohort. Methods In order to investigate whether this variant also predisposes to psoriatic arthritis (PsA), this deletion and 3 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with it were genotyped in a case-control cohort of 650 patients and 937 control individuals of German origin. Results LCE deletion frequency did not significantly differ between patients with PsA and controls (65.0% vs 65.5%). Similarly, no evidence for association to the three SNPs was observed. Discussion This is the first non-human leucocyte antigen (HLA) risk factor predisposing only to skin type of psoriasis, supporting the concept of partially overlapping but different aetiological factors underlying skin and joint manifestations.

OBJECTIVE: To investigate whether MHC class II expression on myeloid cells of patients with treatment-naive early rheumatoid arthritis (RA) correlates with disease progression. METHODS: Monocytes were isolated by negative selection from the peripheral blood of 15 patients with early RA (disease duration < or =12 months), differentiated to macrophages and analysed for MHC class II expression by flowcytometry. The phenotypical data were correlated with clinical disease progression for up to 45 months. RESULTS: Before treatment was initiated, in vitro differentiated macrophages of 10/15 early RA patients expressed MHC class II comparable with macrophages from healthy controls. In sharp contrast, macrophages of the remaining five patients expressed significantly fewer MHC class II molecules. In contrast to patients with normal levels of myeloid cell MHC class II expression, who developed a smouldering, non-progressive disease, patients with decreased expression of MHC class II on macrophages early in their disease developed a continuously active disease as demonstrated by persistently increased disease activity scores (chi(2) = 4.54, P < 0.02) and progressive bone destructions (chi(2) = 5.66, P < 0.02) despite aggressive therapy. CONCLUSION: The level of myeloid cell MHC class II expression in recent onset RA allows a reliable distinction between patients who develop active and destructive RA and patients with a smouldering, slowly progressive disease.

The study aimed to investigate the relation of both negative mucosal potentials (NMP) obtained from respiratory epithelium, and pain ratings to repetitive stimulation with CO2 (21 subjects). Trains of four stimuli of identical intensity (70% v/v) were applied at a constant interseries interval (approximately 60 s) but different interstimulus intervals (ISI) of 2 s or 6 s. At an ISI of 6 s, ratings decreased while they increased at an interval of 2 s (P < 0.01). This change was accompanied by the buildup of burning pain probably relating to the ‘wind-up’ of spinal neurons. In contrast, the decrease of NMP amplitudes was stronger the shorter the ISI (P < 0.01). These findings are in line with the view that the NMP reflects activation of epithelial nociceptors (C-fibers and/or Aδ-fibers).

Background Achieving remission is the most important treatment goal in patients with rheumatoid arthritis (RA). With the development and wider use of highly effective disease modifying anti-rheumatic drugs (DMARD) about half of RA patients reach a state of disease remission, raising the question about tapering or stopping anti-rheumatic treatment. Objectives To assess the effect of a controlled DMARD tapering regimen on treatment costs and work productivity in RA patients in remission Methods 101 RA patients in sustained remission (DAS28 Results In RA patients treated with conventional DMARDs, baseline quarterly treatment costs of 154€ remained stable in arm 1 (156€), while decreasing to 81€ in arm 2 and 75€ in arm 3. In patients treated with biologic DMARDs quarterly treatment costs were 5708€ at baseline. They remained stable in arm1 (5533€) and decreased to 2855€ in arm 2 and 2668€ in arm 3. Overall DMARD costs were reduced by 327.292€ within one year, while outcome was very good with patients either remaining in remission or immediately regaining remission when exposed to original DMARD regimen after relapse. Conclusions Controlled tapering of DMARD treatment leads to effective reduction of treatment costs in RA patients in sustained remission. References ) Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study.Haschka J, Englbrecht M, Hueber AJ, Manger B, Kleyer A, Reiser M, Finzel S, Tony HP, Kleinert S, Feuchtenberger M, Fleck M, Manger K, Ochs W, Schmitt-Haendle M, Wendler J, Schuch F, Ronneberger M, Lorenz HM, Nuesslein H, Alten R, Demary W, Henes J, Schett G, Rech J. Ann Rheum Dis. 2016 Jan;75(1):45–51. doi: 10.1136/annrheumdis-2014-206439. Epub 2015 Feb 6. Disclosure of Interest None declared

Background Autoimmunity is still present in rheumatoid arthritis patients in sustained disease remission. In the absence of inflammation the pattern of autoimmunity against post-translationally modified proteins could potentially impact the course of disease of rheumatoid arthritis patients, espepcially their risk to experience relapse of disease when disease modifying anti-rheumatic drugs (DMARDs) are tapered or stopped Objectives To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in rheumatoid arthritis (RA) patients in sustained remission and to test whether its composition influences the risk for disease relapse when tapering DMARD therapy. Methods Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0–1/10, 2–5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0 to 3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. Results Patient varied in their anti-modified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed sub-specificities. Relapse risk significantly (p=0.011) increased from 18% (0–1/10 reactivities) to 34% (2–5/10) and 55% (>5/10). With respect to specificity groups (0 to 3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. Conclusions The data suggest that the pattern of anti-modified protein antibody response determines the risk of disease relapse in RA patients tapering DMARD therapy. Disclosure of Interest C. Figueiredo: None declared, H. Bang Employee of: Organtec Diagnostica, J. Cobra: None declared, M. Englbrecht: None declared, A. Hueber: None declared, J. Haschka: None declared, B. Manger: None declared, A. Kleyer: None declared, M. Reiser: None declared, S. Finzel: None declared, H.-P. Tony: None declared, S. Kleinert: None declared, J. Wendler: None declared, F. Schuch: None declared, M. Ronneberger: None declared, M. Feuchtenberger: None declared, M. Fleck: None declared, K. Manger: None declared, W. Ochs: None declared, M. Schmitt-Haendle: None declared, H.-M. Lorenz: None declared, H. Nuesslein: None declared, R. Alten: None declared, J. Henes: None declared, K. Krueger: None declared, J. Rech: None declared, G. Schett: None declared

Background Depression is a frequent if not the most frequent comorbidity in patients with rheumatoid arthritis (RA) [1]. Objectives To investigate the prevalence of depressive symptoms in RA patients in a standardized manner in the clinical setting using two previously validated questionnaires and to test for clinical characteristics associated with depressive symptomatology. Methods To assess depressive symptoms the validated 9 item version of the patient health questionnaire (PHQ-9) and the Beck-Depression Inventory II (BDI-II) were used. In addition, demographic background, RA disease activity according to DAS28, RA disease symptoms according to the RAID questionnaire, comorbidities and anti-rheumatic as well as anti-depressive treatment were recorded. Cut-off values for depressive symptomatology were PHQ-9≥5 or BDI-II≥14 (ie mild depressive symptoms or worse). Numbers for frequency of depressive symptomatology were derived by frequency analysis while factors independently associated to depressive symptomatology were investigated by odds ratios and 95% confidence intervals using multiple logistic regression analyses. IRB approval was obtained and all patients completed an informed-consent form prior to participation. Results In 1004 RA-patients (75.1% female, mean age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28(ESR): 2.5±1.2) the prevalence of depressive symptoms was 55.4% according to predefined cut-offs (more restrictive cut-offs indicating moderate depressive symptoms at least, i.e. PHQ-9 ≥10 or BDI-II ≥20 still classified 22.8% of our patients as being depressed). Characteristics independently associated with depressive symptomatology were: age >60 years (OR=0.62 (95%CI: 0.46, 0.83)), DAS28(ESR) ≥3.2 (OR=1.52 (95%CI: 1.03, 2.27)), RAID score >5 (OR=8.28 (95%CI: 5.36, 12.80)) and presence of chronic pain (OR=2.55 (95%CI: 1.42, 4.57)). Only 11.7% of patients classified as having depressive symptoms received anti-depressive drug therapy. Conclusions More than half of RA patients showed symptoms of depression, which were associated with age, RA disease activity, a high impact of RA symptoms on the life of patients and the presence of chronic pain. However, only a small number of RA patients were receiving appropriate anti-depressive therapy. These findings strongly suggest the need for better assessment of depression in routine rheumatologic care. References Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2013. Disclosure of Interest M. Englbrecht Grant/research support from: Research grant for VADERA: Chugai Pharma Europe Ltd. and Roche Pharma AG, R. Alten Grant/research support from: Roche, Chugai, Speakers bureau: Roche, Chugai, M. Aringer Consultant for: Roche, Chugai, Speakers bureau: Roche, Chugai, C. Baerwald: None declared, H. Burkhardt Grant/research support from: Roche, Chugai, Consultant for: Roche, Chugai, N. Eby Consultant for: Fees from Roche Pharma AG for statistical analysis and manuscript preparation during the conduct of the study, J.-P. Flacke Employee of: Roche Pharma AG, G. Fliedner Consultant for: Roche, Chugai, Paid instructor for: Roche, Chugai, B. Gauger Employee of: Roche Pharma AG, U. Henkemeier: None declared, M. Hofmann Employee of: Chugai Pharma Europe Ltd., S. Kleinert Speakers bureau: Abbvie, Chugai, Pfizer, Roche, UCB, Medac, C. Kneitz Grant/research support from: Pfizer, Consultant for: AbbVie, Janssen, Pfizer, Berlin Chemie, Chugai, Roche, Speakers bureau: AbbVie, Janssen, Pfizer, Berlin Chemie, Chugai,Celgenge, Novartis, Roche, MSD, UCB, K. Kruger Employee of: Chugai Pharma Europe Ltd., R. Luthje: None declared, C. Pohl: None declared, G. Schett Grant/research support from: Research grant for VADERA: Chugai Pharma Europe Ltd. and Roche Pharma AG, M. Schmalzing Consultant for: Chugai, Novartis, Roche, Speakers bureau: AbbVie, Actelion, BMS, Chugai, Genzyme, Janssen-Cilag, Novartis, Pfizer, Roche, UCB, A.-K. Tausche: None declared, H. P. Tony Grant/research support from: Roche Pharma AG, Consultant for: Abbvie, BMS, Chugai, Janssen, Lilly, Novartis, Roche, UCB, Speakers bureau: Abbvie, BMS, Chugai, Janssen, Lilly, Novartis, Roche, UCB, J. Wendler Consultant for: Roche, Chugai, Speakers bureau: Roche, Chugai

Background Early stages of rheumatic diseases (0–12 weeks) including rheumatoid arthritis (RA) are still difficult to diagnose. For this reason, incorrect referrals to a rheumatologist result in a high use of resources in outpatient clinics. Objectives Implementation of a structured screening system for selecting and treating patients (pts) with RA or other rheumatic and musculoskeletal diseases (RMD). Methods 98 pts visited a screening appointment for early arthritis (EA) between February 2015 and September 2015 in special EA departments. Inclusion criterion was arthritis ≥ one joint for less than one year recorded by phone. Qualified health professional assistants (HPA) conducted the phone call. Upon screening, all pts filled in a tablet based questionnaire to be developed for future online use about their symptoms. Subsequently, 53 pts (group 1) were seen first by an HPA who analysed the questionnaire and performed the joint count. Based on these findings, the HPA made a suspected diagnosis. Afterwards, also a rheumatologist saw these pts and made a suspected diagnosis. In comparison, the rheumatologist directly examined 45 pts without an HPA (group 2). In both groups, typical clinical findings led to a new appointment, or in acute cases, treatment was started immediately. If an RMD was suspected or laboratory parameters were abnormal, pts received a second appointment as well. The documentation of the real-life data was carried out by the Medpath © system based on medical and flexible adaptable paths. Results Mean duration between phone call and screening was 19.6±12.8 days. Pts had an age of 18–80 years (mean 51.1±15.5 years), and 73 pts (74.5%) were female. Although all pts had reported symptoms of less than one year over the phone, only 70 pts (71.4%) fulfilled this criterion when asked in the questionnaire. In group 1, according to the HPA 22 of 53 (41.5%) pts had an RMD upon screening. The suspected diagnoses of HPA and rheumatologist corresponded in 43 of 53 (81.1%) pts in the screening. In group 2, the rheumatologist suspected 14 of 45 (31.1%) pts having an RMD in the first visit. 59 (60.2%) pts had no RMD. 23 (23.5%) pts had RA that was seropositive in 14 (14.3%) pts. All RA pts were recommended a therapy with conventional disease modifying antirheumatic drugs (cDMARDs) and glucocorticoids (GC), which 21 (21.4%) pts started 17.2±27.6 days after screening. 3 (3%) pts initially had a preclinical seropositive RA, which changed into definite RA in need for treatment with cDMARDs after 191 days in one patient. 3 (3%) pts received inpatient treatment and systemic lupus erythematosus was diagnosed in one case. Conclusions The structured screening system efficiently selects pts with RMDs and leads to treating RMD at an early stage in times of limited resources. Acknowledgement Abbvie supports the project within the T2T Initiative Germany. Disclosure of Interest None declared

Variants in two genes of the IL-23 receptor (R) pathway have recently been shown to be associated with psoriasis vulgaris (PV). We were interested whether the risk conferred by these variants differs between psoriatic skin and joint disease. Four variants of the IL12B and IL23R genes were analyzed in 1,114 PV patients, 748 patients with psoriatic arthritis (PA) and 937 healthy controls before and after stratification for the major psoriasis risk allele at psoriasis susceptibility locus 1 ( PSORS1 ). For both PA and PV, we detected the strongest association with two IL12B single-nucleotide polymorphisms and the corresponding haplotype as reflected by minimal P -values of 10 -7 and highest odds ratios of 1.50 (1.28–1.75) for rs6887695 in PA patients and 1.50 (1.27–1.76) for rs3212227 in the PV cohort, respectively. For IL23R , only rs11209026 showed an association. The results remained significant after correction for multiple testing. No difference was observed after stratification for the PSORS1 risk allele. While confirming recent reports on variants of the IL-23R pathway as susceptibility factors for PV, our study is the first to extend analysis of both genes to PA. However, our results indicate that these variants are not specific risk factors for arthritis, but relevant for susceptibility to psoriasis in general.

Background Due to improved therapeutic management a steadily increasing number of rheumatoid arthritis (RA) patients reach stable remission of disease. Data on withdrawal of medication after sustained remission are limited, though it is important for economic and safety reasons. The RETRO study represents a real-life study addressing different strategies of reduction of DMARD therapy in RA patients in stable disease remission. Objectives To prospectively analyze the risk for disease relapses in rheumatoid arthritis (RA) patients in sustained remission, either continuing, tapering, or stopping disease modifying anti-rheumatic drugs (DMARD). Methods RETRO is a phase 3, multicenter, randomized, controlled, open, prospective, parallel-group trial (EudraCT Number: 2009-015740-42). Patients, fulfilling the ACR/EULAR2010 criteria for RA were enrolled into the study if they were in clinical remission (DAS28-ESR 2.6) the original therapy was restarted. Results 101 patients (61.4% females, 60% ACPA positive, 63% RF positive; 37.6% biologic therapy, 80.2% MTX, 7.9% other DMARDs) finished the one year endpoint: 38 patients in arm 1 (age 55.8±13.9y, disease duration 6.8±5.9y, remission 20.9±16.7mo), 36 patients in arm 2 (age 54.1±13.1y, disease duration 8.6±7.7y, remission 14.5±12.7mo) and 27 patients in arm 3 (age 54.8±12.3y, disease duration 5.6±7.0y, remission 17.6±19.5mo). Of 101 patients, 66.3% were still in remission at 12 mo. Significantly more patients flared in reduction arm 2 (38.9%, c2(1)=5.0, p=0.036) and arm 3 (51.9%, c2(1)=9.6, p=0.003) compared to control arm 1 (15.8%), while there was no significant difference between the two reduction arms (c2(1)=1.1, p=0.443). With multivariate logistic regression ACPA positivity (p=0.03) and treatment reduction (arm2 p=0.01, arm3 p=0.003) were detected as predictors for flares. Conclusions This study is a prospective real life treatment strategy study investigating the effect of reduction and discontinuation of DMARD therapy in RA patients in stable remission. Presence of ACPA but not RF was the only predictor for recurrence of disease. Disclosure of Interest None declared

Optimal treatment for patients with relapsing lupus nephritis remains unclear. The ability of 15-deoxyspergualin (gusperimus; 15-DSG) to suppress systemic lupus erythematosus (SLE)-like diseases has been demonstrated in animals and humans.1–4 15-DSG exerted no nephrotoxicity or hepatotoxicity but reversibly induced leucocytopenia.5,6 In this study we aimed at evaluating the safety of 15-DSG in the treatment of glomerulonephritis associated with SLE. Table 1 shows the patient characteristics. View this table: Table 1 Details of the patients’ history, especially previous immunosuppressive treatment, signs of SLE-GN activity or general SLE activity at entry, and indicators for response during/after 15-DSG treatment 15-DSG was provided by Nippon Kayaku Co Ltd, Tokyo, Japan. Patients gave their informed consent, and 15-DSG 0.5 mg/kg normal body weight (height in cm minus 100)/day was self administered subcutaneously for 14 days, followed by a break of 7 days ( = 1 cycle). The dose was adjusted (dependent on efficacy or safety, or both) after cycles 4 and 6 to 0.35 mg/kg and 0.25 mg/kg, or 0.7 mg/kg and 1.0 mg/kg. ### Patient 1 After a bolus, daily …

Objective Tumor necrosis factor (TNF)–neutralizing agents are the most successful means of ameliorating systemic autoimmune inflammation. Neutralization of TNF, however, is often associated with the development of autoantibodies, particularly to nuclear antigens, and the mechanisms of this are unknown. We undertook this study to analyze the effect of TNF and its neutralization on the expression of major histocompatibility complex class II molecules and on the function of antigen-presenting myeloid cells in rheumatoid arthritis (RA). Methods Monocytes were isolated from the peripheral blood of RA patients before and after anti-TNF monoclonal antibody (mAb) treatment and from the peripheral blood of controls by negative selection, differentiated in vitro to macrophages, and analyzed by flow cytometry for HLA–DR expression. T cell responses to activation by myeloid cells were assessed in proliferation assays, and messenger RNA (mRNA) levels of the class II transactivator (CIITA) were determined by semiquantitative reverse transcriptase–polymerase chain reaction. Results HLA–DR expression was significantly reduced on myeloid cells from RA patients with active disease, but was increased to normal levels after anti-TNF mAb treatment. Concordantly, in vitro application of TNF to monocytes from healthy individuals reduced their ability to up-regulate HLA–DR during differentiation to macrophages and, importantly, inhibited their ability to stimulate T cells in mixed lymphocyte reactions. Molecular analysis revealed that the effect of TNF on HLA–DR expression was mediated via suppression of the transcription factor CIITA. Conclusion The data indicate that TNF decreases HLA–DR expression by reducing CIITA mRNA levels in myeloid cells, functionally resulting in a decreased capacity of myeloid cells to stimulate T cells. Concordantly, ameliorating disease activity in chronic inflammatory diseases by neutralizing TNF restores expression of HLA–DR on myeloid cells as well as the ability of myeloid cells to stimulate T cells. Thus, anti-TNF treatment might lead to augmented T cell activation by myeloid cells, thereby promoting immune responses to (auto)antigens and the development of antinuclear antibodies that are frequently associated with anti-TNF therapy.

Pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) is unresolved. Dysregulation of programmed cell death is discussed as a pathogenetic factor. We have previously shown that increased in vitro apoptosis of cultured peripheral blood mononuclear cells (PBMC) is nonspecific for SLE. Importantly, however, in recent experiments with SLE PBMC from patients with infections and fever in vitro apoptosis was strongly accelerated. We therefore hypothesized that regulation of apoptosis might be disturbed in activated SLE lymphocytes. Thus, we generated phytohemagglutinine (PHA)/IL-2 stimulated lymphoblasts in vitro. These lymphoblasts readily undergo apoptosis after culture in cytokine-free medium, and can be rescued by addition of gammac-chain cytokines IL-2, -4, -7, or -15. In lymphoblasts from 60 SLE patients tested in comparison to lymphoblasts from normal donors cultured in parallel, we found significant hyporesponsiveness to gammac-chain cytokines in SLE cells. Minor differences were also seen in lymphoblasts from patients with other systemic autoimmunopathies (mixed connective tissue disease, vasculitis, n=49)and in lymphoblasts from patients with other autoimmune diseases (mainly rheumatoid or reactive arthritis, myositis, n=44). In patients with high erythrocyte sedimentation rate (25 mm/h), TNF-alpha (6.5 pg/ml) or IL-12 (4.7 pg/ml) serum levels or detectable IFN-gamma concentrations hyporesponsiveness to gammac-chain cytokines was even more pronounced in SLE lymphoblasts, but not in lymphoblasts from the other groups. Moreover, increased apoptosis was seen in lymphoblasts from SLE patients with decreased complement (C)4 or elevated dsDNA antibody levels. In conclusion, these data suggest that in SLE patients with increased inflammatory activity and/or Th1 dominance signaling through gammac-chain cytokine receptors is deteriorated, leading to facilitated apoptosis of activated lymphocytes and enlarged onflow of apoptotic material.

Background The detection of joint swelling caused by synovitis is important for the diagnosis and assessment of inflammatory arthritis. Ultrasound (US) and MRI have proven to be more sensitive and reliable than physical examination, but a comprehensive examination of affected joints with these techniques is time consuming and expensive. The automated breast volume scanner (ABVS) was developed to acquire serial B-mode pictures of the female breast and these data can be analysed in all three dimensions. Objectives To analyse the value of automated grey scale B mode US employing the ABVS system in detecting synovitis of the finger joints compared to manual ultrasound and physical examination, using MRI as gold standard. Methods 19 consecutive patients suffering from rheumatoid (n=15) or psoriatic (n=4) arthritis with at least one swollen finger joint were included. Automated and manual US were conducted using the ACUSON S2000™. The ABVS transducer was equipped with a linear array used with a frequency of 11 MHz. Each automatic sweep of the scanner generated 15.4 x 16.8 x 2.5 cm volume data sets. The system was set to perform an automatic scanning time of 65 s per scan with a slice thickness of 0.5 mm. The dorsal and palmar side of each hand were scanned separately. Multiplanar reconstruction enabled examination of the images at multiple levels for the presence of synovitis. Results Automated US detected 12.0, manual ultrasound 14.2, MRI 13.4, and clinical examination 4.1 swollen joints on average, respectively, per patient. The inter-observer reliability of both assessors for automated and manual US, MRI, and physical examination, was 66.9%, 72.7%, 95.1%, and 88.9%, respectively. A double assessor detection of joint swelling with MRI was used as gold standard. For the other methods, single observer detection was chosen. 84.3% of the joints classified as positive on MRI were confirmed by automated ultrasound, 85.5% on manual US, and 36.0 on physical examination. This translated into a sensitivity of 83.5%, 85.5%, and 36.0% for the three methods, respectively. Conclusions Automated US is a simple and time sparing option for the effective detection of synovitis in patients with inflammatory arthritis. Disclosure of Interest R. Mueller: None declared, M. Gruenke: None declared, J. Wendler: None declared, F. Schuch: None declared, H.-P. Karina: None declared, I. Boettger: None declared, R. Jakobs Employee of: Siemens, H. Schulze-Koops: None declared, J. von Kempis: None declared DOI 10.1136/annrheumdis-2014-eular.2059

Background Rheumatoid arthritis (RA) is likely to be driven by activated Th1 cells. In contrast, Th2 cells and their cytokines, in particular IL-4, are rarely found in RA. Objectives To determine whether memory or naive CD4pos T cells in RA manifest an intrinsic bias for Th1 differentiation. Methods Th differentiation was assessed in an ex vivo cell culture system in CD4pos, CD45RApos (naive) and CD45RO pos (memory) T cells isolated from the peripheral blood from patients with active, early RA (mean disease duration Results Th2 effectors could be induced from memory T cells in all healthy controls by stimulation with anti-CD28 and IL-4 but in only one third of the RA patients. Priming conditions that were optimal for the differentiation of Th2 effectors from memory T cells, e.g. priming with anti-CD28 and IL-4 in the absence of TCR-ligation, did not result in Th2 differentiation from resting naive T cells in any individual. In contrast to memory T cells, however, Th2 cells could be induced from naive T cells in all healthy donors and in all RA patients by priming with anti-CD3 in the presence of anti-CD28. Conclusion CD4pos memory T cells from the majority of patients with early RA manifest a deficiency in the capacity to differentiate into Th2 effectors. In contrast, naive T cells are capable of differentiating into Th2 cells with appropriate stimulation suggesting that the bias in Th1 differentiation of most RA patients is acquired during T cell maturation presumably in response to antigenic stimulation.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, which is likely to be driven by activated pro-inflammatory Th1 cells. In contrast, Th2 cells and their cytokines, in particular IL-4 are rarely found in RA. It could recently be demonstrated that memory T cells from patients with early RA manifest a profound functional deficit in that they cannot differentiate into Th2 cells even at very early stages of the disease. The inability of memory T cells to mount immunomodulatory Th2 effectors might contribute to the Th1 bias in RA and, thus, might by critically involved in the initiation of chronic autoimmune inflammation. The mechanisms, however, involved in this abnormality have not been delineated in detail. We have recently established a system to analyse T cell differentiation in vitro and have identified molecular mechanisms regulating Th2 effector generation in healthy individuals. In the current proposal, molecular mechanisms will be identified that are involved in the development of Th1 mediated immunity in patients with very early rheumatoid arthritis (symptoms at time of blood collection of ≤2 weeks) using gene chip microarray technology. Selected candidate genes associated with the Th2 cell differentiation defect will be tested for their functional significance in biological assays. The definition of mechanisms contributing to the Th1 differentiation bias in very early RA will provide important insights into the pathogenesis of the disease, in particular into the initial steps of the evolving immune response, and might lead to the development of novel therapeutic strategies.

Background Anti-TNFα monoclonal antibodies (mAbs) have recently been introduced as a treatment for rheumatoid arthritis (RA). Whereas anti-TNFα mAbs are potent inhibitors of inflammation, their effect on the activation and differentiation of myeloid cells has not been elucidated. Objectives To investigate the function and the phenotype of monocytes from RA patients during their differentiation to macrophages in vitro before and 4 weeks after a single administration of mAbs to TNFα. Methods Patients with highly active disease who were resistant to treatment with disease modifying antirheumatic drugs and corticosteroids were included into the study. Monocytes were isolated from the peripheral blood by negative selection, and their phenotype was analysed directly after isolation and during differentiation to macrophages. Results Treatment was effective as 4 weeks after mAb application the inflammatory activity, as assesed by DAS 28, and the sedimentation rate were significantly reduced. Whereas the expression of HLA-DR, CD40, CD25, CD80, CD86, CD14 and CD68 in freshly isolated monocytes was similar before and after treatment with anti-TNFα, marked differences were found during maturation. After treatment, upregulation of HLA-DR and CD80 was markedly enhanced during macrophage differentiation. In contrast, the expression of CD40 was decreased after treatment. Conclusion The results demonstrate that a single therapy with anti-TNFα mAbs alters the ability of macrophages to upregulate molecules involved in cellular inflammation even 4 weeks after treatment. However, as those changes were associated with clinical benefit, the data suggest that the clinical effect of anti-TNFα mAbs treatment is not restricted to neutralising TNFα but may be due to long lasting anti-inflammatory alterations that remain active even after the mAb has been cleared from the circulation.

Background Evidence suggests that monocyte precursor cells in rheumatoid arthritis (RA) might become partially activated in the bone marrow or the peripheral blood before they enter the rheumatoid synovium. However, whether this is the result of pro-inflammatory cytokines leaking from the inflamed synovium into the circulation or rather a functional abnormality of myeloid cells has not yet been conclusively delineated. Objectives To test the hypothesis that monocytes in RA might express an intrinsic abnormality for activation, we investigated the function and the phenotype of peripheral blood monocytes from patients with RA and healthy controls in vitro. Methods Monocytes were isolated by negative selection from patients with active, early RA and from patients with long standing RA under effective anti-inflammatory therapy with disease modifying antirheumatic drugs (DMARDs). A cell culture system was employed that permitted the differentiation of monocytes to macrophages. Expression of surface molecules indicative of activation and/or differentiation was assessed by flow cytometry. Results No differences were detected for the expression of HLA-DR, CD14, CD40, CD68, CD80 and CD86 on freshly isolated monocytes between patients and controls. During differentiation to macrophages, the expression of HLA-DR, CD14 and CD80 was increased in RA monocytes. Interestingly, patients with untreated, active early disease manifested an even higher propensity to upregulate HLA-DR during differentiation compared to patients with long standing disease under effective anti-inflammatory therapy. In contrast, the expression of CD40, CD68 and CD86 was reduced in myeloid cells from RA patients during differentiation. This feature was more pronounced in patients with long standing disease, but was not correlated with clinical activity. Conclusion The data indicate that monocytes from RA patients might have an intrinsically increased ability for activation during differentiation. This ability might contribute to clinical disease activity and emphasises the systemic nature of the disease. The data further suggest that long standing disease might alter the functional phenotype of circulating monocytes. However, the contribution of continuous treatment with DMARDs to this phenomenon remains to be elucidated.