Search

ObjectiveThe Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health.MethodsPatients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included. Patients received questionnaires addressing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), mental health (5-item World Health Organization Well-Being Index [WHO-5]), and global functioning (ASAS HI). Standardized response means (SRMs) were calculated to compare the sensitivity to change of different variables.ResultsSix hundred and sixty-seven patients were included, 552 treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and 115 with conventional synthetic DMARDs and/or nonsteroidal antiinflammatory drugs (control group). Between baseline and month 12, the mean ASAS HI declined from 6.9 to 5.1 in the bDMARD group and from 5.9 to 5.6 in the conventionally treated group. In the bDMARD group, the SRM of ASAS HI was 0.52, compared to 0.59 for BASFI, 0.65 for WHO-5, 0.73 for BASDAI, and 0.90 for ASDAS. The following ASAS HI domains were most frequently affected: pain (78% agreed), maintaining body position (75%), and energy/drive (73%). In the patients receiving bDMARDs, there was an improvement in all items. In the control group, the largest improvement was seen in pain.ConclusionAs expected, ASDAS and BASDAI as disease activity scores showed high sensitivity to change, whereas changes in physical function (BASFI), mental health (WHO-5), and the broader concept of functioning and health (ASAS HI) were moderate.

BackgroundPsoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) show certain overlaps: A subset of patients with PsA can develop axial involvement (axial PsA, axPsA), while a subset of patients with axSpA presents with psoriasis (axSpA+pso). Treatment strategy for axPsA is mostly based on axSpA evidence.ObjectivesTo compare demographic and disease-specific parameters of axPsA and axSpA+pso.MethodsRABBIT-SpA is a prospective longitudinal cohort study. AxPsA was defined based on (1) clinical judgement by rheumatologists; (2) imaging (sacroiliitis according to modified New York criteria in radiographs or signs of active inflammation in MRI or syndesmophytes/ankylosis in radiographs or signs of active inflammation in spine MRI). axSpA was stratified into axSpA+pso and axSpA without pso.ResultsPsoriasis was documented in 181/1428 axSpA patients (13%). Of 1395 PsA patients, 359 (26%) showed axial involvement. 297 patients (21%) fulfilled the clinical definition and 196 (14%) the imaging definition of axial manifestation of PsA. AxSpA+pso differed from axPsA regardless whether clinical or imaging definition was used. axPsA patients were older, more often female and less often HLA-B27+. Peripheral manifestations were more often present in axPsA than in axSpA+pso, whereas uveitis and inflammatory bowel disease were more common in axSpA+pso. Burden of disease (patient global, pain, physician global) was similar among axPsA and axSpA+pso patients.ConclusionsAxPsA differs from axSpA+pso in its clinical manifestations, irrespective of whether axPsA is defined clinically or by imaging. These findings support the hypothesis that axSpA and PsA with axial involvement are distinct entities, so extrapolation of treatment data from randomised controlled trials in axSpA should be performed with caution.

The biomedical approach to medical knowledge is widely accepted around the world. This article considers whether the incorporated aspects of physician-patient interaction have become similarly common across the globe by comparing the gestures that physicians use in their interactions with patients. Up to this point, there has been little research on physicians’ use of gestures in health-care settings. We explore how—in four university hospitals in Turkey, the People’s Republic of China, The Netherlands and Germany—physicians use gesture in their discussions with simulated patients about the condition of heart failure. Our analysis confirms the importance of gestures for organising both the personal interaction and the knowledge transfer between physician and patient. From the perspective of global comparison, it is notable that physicians in all four hospitals used similar gestures. This demonstrates the globality of biomedical knowledge in an embodied mode. Physicians used gestures for a range of purposes, including to convey the idea of an ‘anatomical map’ and for constructing visual models of (patho-)physiological processes. Since biomedical language is rife with metaphor, it was not surprising that we also identified an accompanying metaphorical gesture which has a similar form in the various locations that were part of the study. in press

ObjectiveTo investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology.MethodsProspectively followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed.ResultsIn a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points.ConclusionsPooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

BackgroundInhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD).ObjectiveTo investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.MethodsPatients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).ResultsAt enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.ConclusionAlthough the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.

Durch die Zulassung einer Reihe neuer Biologika mit verschiedenen Wirkmechanismen sowie den zunehmenden Einsatz von Biosimilars hat sich die Behandlung der axialen Spondyloarthritis (axSpA) und der Psoriasisarthritis (PsA) in den letzten Jahren enorm gewandelt. Die Datenlage hinsichtlich der langfristigen Sicherheit und Wirksamkeit unter Alltagsbedingungen ist bisher nicht ausreichend. Deshalb wurde im Deutschen Rheuma-Forschungszentrum eine neue Kohortenstudie begonnen. Vorstellung erster Ergebnisse aus dem im Mai 2017 gestarteten Register RABBIT-SpA. Prospektive longitudinale Kohortenstudie, angelehnt an das RABBIT-Design: Einschluss bei Beginn oder Wechsel einer Therapie entweder in die Vergleichsgruppe (konventionelle systemische Therapie, einschlieslich NSAR) oder in die Gruppe der sog. Indexmedikamente. Die Beobachtungszeit sollte pro Patient mindestens 5 und moglichst 10 Jahre betragen. RABBIT-SpA benutzt ein Internet-gestutztes Dokumentationssystem. Bis Mitte Dezember 2018 wurden 514 axSpA-Patienten in RABBIT-SpA dokumentiert, 410 mit einem Indexmedikament und 104 mit einer konventionellen Therapie. Zwischen diesen Behandlungsgruppen bestehen Unterschiede z. B. in der Krankheitsdauer und in Parametern der Krankheitsaktivitat. Weiterhin fallt auf, dass bei den axSpA-Patienten ca. 5 Jahre zwischen dem Symptombeginn und der Diagnosesicherung liegen. Von den 355 PsA-Patienten wurden 265 mit einem Indexmedikament und 90 mit einer konventionellen Therapie eingeschlossen. Bei 86 % der PsA-Patienten besteht ein dominant peripherer Befall. Die Anzahl der druckschmerzhaften Gelenke liegt im Mittel bei 8 und die Anzahl der geschwollenen Gelenke im Mittel bei 4. Das online-Register RABBIT-SpA wird von den beteiligten rheumatologischen Einrichtungen gut angenommen. Die elektronische Erfassung der Patientendaten kann in einer angemessenen Zeit und mit einem vertretbaren Aufwand erfolgen. Die Teilnahme weiterer rheumatologischer Einrichtungen an RABBIT-SpA ist jederzeit moglich.

Objective To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long-term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA). Methods Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0-4 per SI joint). A sacroiliitis sum score (total range 0-8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system. Results Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow-up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, -0.27 ± 0.76, and -0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C-reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score. Conclusion Our findings indicate that long-term anti-TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression.

Zusammenfassung Eine Analyse globaler Ungleichheiten kann nicht im Rahmen des Nationalstaats erfolgen. Zentral ist vielmehr das Verhaltnis zwischen den Ressourcen von Personen und den vielfaltigen – auch transnationalen – Kontexten, in denen die Ressourcen Wert gewinnen. Der Artikel zeigt an Fallvergleichen zwischen Sud-Nord-Migrant_innen, die ihre soziale Lage im Zuge der Migration deutlich verbessern konnten, wie diese an eine Vielzahl von Kontexten anschliesen und so strukturelle Hurden uberwinden. Dabei wird analytisch zwischen sozial differenzierten, politisch umkampften und territorial gebundenen Kontextrelationen unterschieden werden. Da diese Kontextrelationen oft transnational sind, wird eine Methode wie die hier verwendete Dokumentarische Methode benotigt, die Kontextrelationen nicht nur uber Selbstpositionierungen und den Lebensmittelpunkt einer Person erfasst, sondern die auch implizite Lagerungsahnlichkeiten rekonstruiert. Mit Hilfe (trans-)nationaler Vergleichsstrategien analysiert der Beitrag das komplexe Verhaltnis von Personen zu (trans-)nationalen ungleichheitsrelevanten Kontexten und die daraus resultierenden Lebenschancen. Schlagworter: Globale Ungleichheit, soziale Mobilitat, Qualitative Methoden, Migration, Rassismus ----- Social mobility and migration. Global inequalities viewed through the lens of qualitative case comparison Abstract The analysis of global inequalities must move beyond the nation-state frame and consider the – potentially transnational – contexts in which the resources of persons gain value. The article uses case comparisons between South-North migrants, who were able to significantly improve their social position in the course of migration, in order to show how they overcome structural barriers by connecting to a variety of contexts. Analytically we distinguish socially differentiated, politically contested and territorially bounded context relations. Considering that context relations often have a transnational scope, we need a method such as the documentary method used in this article, which reconstructs context relations not only from self-identification and place of residence, but also from implicit habitual homologies. With the help of multiple (trans-)national comparison the article shows how the complex relationship between persons and (trans-)national contexts promotes or obstructs social mobility. Keywords: Global inequalities, social mobility, qualitative research methods, migration, racism ----- Bibliographie: Weis, Anja/Kellmer, Ariana: Soziale Aufstiege durch Migration. Lassen sich globale Ungleichheiten durch fallvergleichende qualitative Forschung rekonstruieren?, ZQF – Zeitschrift fur Qualitative Forschung, 1-2/2018, S. 97-112. https://doi.org/10.3224/zqf.v19i1-2.07

Background Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research. Methods An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This “conflict catalog” was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried. Results Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40–64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59–69% were answered. The most common missing values were CRP, ESR, Schober’s test, data on systemic glucocorticoid therapy, and presence of enthesitis. Conclusion Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

Entrustable Professional Activities in Graduate Medical Education in Psychiatry: A Promising Concept

The editorial summarizes the main conceptual and epistemological challenges of theorizing on society across borders. Its particular aim is to initiate the dialogue between theories of society and cross-border studies that address global, transnational and postcolonial relations. In essence, this special issue addresses four interrelated concerns of studying societal processes across borders. The first of these concerns is prompted by a decades-old critique of methodological nationalism. The second concern addresses the question of how can ‘society’ and the boundaries of ‘societalization’ be conceptualized, if global, transnational and postcolonial processes straddle the boundaries of nation-states? The third concern relates to the fact that sociological ‘grand’ theories have been criticized for failing to analyze recent developments of societies on a meso- and micro-level. Fourthly, a conversation between social theory and cross-border studies is also challenged by epistemic inequalities. Therefore, theories of society should be able to take into account not only the ‘grand scale’ of societal contexts and societal changes but also the positionality of the theorizing subject within global asymmetries of power.

Globalization and cross-border studies have changed the ways in which sociological theorists think about space. Rather than viewing society as integrated, placing individual and collective actors in clearly bounded spaces nested within each other, this article combines several differentiation theories of society as a first step towards achieving an abstract language that can account for a plurality of comprehensive social contexts, thus relating actors to socio-spatial contexts in various ways. Starting with Simmel, the article discusses how some social contexts, such as the state, use the territory to gain exclusivity, whereas other social contexts are non-territorial in nature. Further types combine social and spatial differentiation. The article expands on Simmel’s socio-spatial forms with the help of newer systems theories proposed by Luhmann and Walby and Bourdieu’s field theory. The article provides cross-border and transnational studies with a comprehensive typology of socio-spatial forms. The argument contributes to global studies by considering a plurality of content-differentiated globalization logics and by clarifying the relationship between macro-social contexts and actors. In organizations, networks and professions, content differentiation, spatial segmentation and actors’ contestation intertwine.

Background:Spondyloarthritis (SpA) is a severe chronic inflammatory disease, which affects quality of life and functional status. It frequently occurs in women of childbearing age. Active disease and TNFi discontinuation at early pregnancy were found to be risk factors for flares during pregnancy (1).Objectives:To compare disease activity during pregnancy in patients with or without bDMARD exposure at conception and during pregnancy and to assess pregnancy outcomes.Methods:RHEKISS is a prospective longitudinal cohort study including patients with confirmed diagnose of inflammatory rheumatic disease. Pregnant patients are eligible to be enrolled until the 20th week of gestation regardless of drug treatment. During observation, information on treatment, disease and pregnancy course, and outcome is collected from rheumatologists and patients. For this analysis, pregnancies of patients with SpA were selected and stratified into three groups according to their exposure to bDMARDs.Results:Of 140 SpA pregnancies included, 74 (53%) were not exposed to bDMARDs at conception (group 1), 38 (27%) were exposed to bDMARDs at conception, but not during pregnancy (group 2) and 28 (20%) were continuously exposed to bDMARDs at conception and during pregnancy (group 3). Certolizumab (50%), Adalimumab (20%), Etanercept (8%) and Infliximab (8%) were the most frequently prescribed bDMARDs at beginning of pregnancy. Baseline characteristics according to treatment exposure are shown in Table 1. Frequency of flares was highest in group 2: 21%, 38%, and 39% of patients flared during the 1st, 2nd, and 3rd trimester. These rates were 20%, 25%, and 21% in group 1 and 8%, 20%, and zero in group 3. The difference in flare rates was also mirrored in the course of physician assessed global disease activity (Figure 1). Whereas patients in group 1 seemed to have a quite stable disease activity during pregnancy, those who were in group 2 had an increasing activity of disease during pregnancy with an even higher increase of disease activity after giving birth. Patients in group 3 had the lowest disease activity.Of 137 singleton pregnancies, 130 (95%) ended in live birth. Of 6 spontaneous abortions 2 were in every of the three groups. One pregnancy in group 1 was terminated in gestational week 22 due to suspect malformation. One baby of the triple pregnancy was born and two aborted. All babies of the twin pregnancies were born healthy.Conclusion:SpA patients treated with bDMARDs at conception are not at higher risk for adverse pregnancy outcomes. Our results in a larger patient population confirmed that discontinuation of bDMARDs after conception is associated with increased disease activity during pregnancy and after birth and a higher risk of flares.References:[1]van den Brandt S et al., Arthritis Res Ther. 2017; 19(1):64.Table 1.Baseline characteristics; numbers are n (%) if not otherwise specified; * value at beginning of pregnancy: first 22 weeks after conceptionParameterno bDMARD at conception (group 1)n=74bDMARD at conception anddiscontinuedduring pregnancy(group 2)n=38bDMARD at conception andcontinuedduring pregnancy (group 3)n=28Totaln=140Singleton72 (97)37 (97.4)28 (100)137 (97.9)Twin1 (1.4)1 (2.6)02 (1.4)Triple1 (1.4)001 (0.7)New-York criteria fulfilled21 (33)17 (49)10 (48)48 (40)disease duration in years, mean (SD)6.4 (5.9)7 (4.1)5.8 (4)6.4 (5.1)age*, mean (SD)33.4 (4.9)32.3 (4)31.6 (3.4)32.7 (4.4)severity of illness*: asymptomatic4 (6)0 (0)3 (14)7 (6) mild31 (48)6 (17)4 (19)41 (34) moderate24 (38)21 (60)14 (67)59 (49) severe5 (8)8 (23)013 (11)HLA-B27 positive41 (62)24 (80)15 (75)80 (69)CRP in mg/l *, mean (SD)6.6 (8.2)5.4 (8.2)5.2 (4.9)6 (7.6)CRP >5mg/l *25 (41)9 (30)8 (35)42 (37)physician global* (NRS 0-10), mean (SD)2.6 (2)2.3 (2.5)1.7 (1.4)2.4 (2.1)BASDAI* (0-10), mean (SD)3.2 (2)2.9 (2.3)2.8 (1.5)3.1 (2)patient global* (NRS 0-10), mean (SD)3.3 (2.7)3 (2.8)3 (2.3)3.1 (2.6)Figure 1Course of physician assessed global disease activityDisclosure of Interests:None declared.

Background:The treatment of patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) has been revolutionised by the introduction of biologic DMARDs targeting TNF, IL17, and IL23 inhibitors (i). In Germany, about 30-50% of axSpA and PsA patients receive treatment with bDMARDs. Although many patients benefit from these drugs, in some patients effectiveness of the standard dose may be insufficient and higher doses are used.Objectives:To describe dosing of TNFi and non-TNFi bDMARDs over a 2 year period in a real world cohort of patients with axSpA and PsA managed by rheumatologists.Methods:RABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients enrolled at the start of a new conventional treatment (including NSAID) or b/tsDMARD treatment. Description of dosing of TNFi (adalimumab bio-original (bo), adalimumab bio-similar (bs), etanercept bo, etanercept bs, golimumab, certolizumab) in comparison to nonTNFi-bDMARDs (secukinumab, ustekinumab, ixekizumab, guselkumab) in axSpA and PsA. Standard dosing was defined according to the current labels for axSpA and PsA.Results:1628 patients (axSpA: n=903, PsA: n=725) were included in this analysis. At inclusion mean age was 44 years in axSpA and 51 years in PsA. 44% of patients with axSpA and 58% of those with PsA were female. The mean disease duration of axSpA was 7.6 years, of PsA 6.4 years.Standard doses of TNFi were used during a 2 year period in > 90% of patients with axSpA and PsA (Figure 1). In contrast, standard doses of non-TNFi-bDMARDs were only used in 70-80% of patients. The percentage of documented higher doses in patients with axSpA ranged from 20-30% at different time points. In PsA, this percentage increased from 27% at baseline to 44% at 2 years. On the other hand, TNFi were used in lower doses than the label in up to 9% and 7 % of patients with axSpA and PsA, respectively, after 2 years.Figure 1.Percentages of patients with axSpA or PsA who received less than, equal to, or more than the approved doses of bDMARDs at baseline and at 5 follow-up visits.Conclusion:While TNFi are used in licensed doses in most patients, non-TNFi-bDMARDs were often used in higher doses, which corresponds to higher doses approved in other indications like psoriasis. The effectiveness of this treatment strategy in axSpA and PsA needs to be analysed further.Acknowledgements:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB, and Viatris.We thank all participating patients and rheumatologists.Disclosure of Interests:Anne Regierer Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB, and Viatris., Anja Weiß Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB, and Viatris., Denis Poddubnyy: None declared, Herbert Kellner: None declared, Frank Behrens: None declared, Georg Schett: None declared, Juergen Braun: None declared, Joachim Sieper: None declared, Anja Strangfeld Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB, and Viatris

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system as well as skin and nails. The prevalence of depression in psoriasis and PsA is high and ranges from 7-40% [1]. Persistent depressive mood may influence disease activity outcome in PsA, especially patient-reported outcomes.Objectives:To assess the correlation of depressive symptoms with PsA-specific outcome parameters.Methods:RABBIT-SpA is a prospective longitudinal cohort study including PsA patients enrolled at start of a new conventional treatment or b/tsDMARD treatment. In regularly provided follow-up questionnaires, physician- and patient-reported information on the disease course including the depression screening tool WHO-5 to assess mental health is collected. For the current analysis, the WHO-5 score was categorised into 4 groups using validated cut-offs: severe depressive symptoms 50. Spearman correlation coefficient was calculated to analyse the relationship between the WHO-5 score and various PsA related outcome parameters.Results:936 PsA patients were included. Baseline characteristics are shown in Table 1. In 411 patients (43.9%) the WHO-5 score indicated well-being, 249 (26.6%) had mild depressive, 203 (21.7%) moderate depressive and 73 patients (7.8%) severe depressive symptoms. WHO-5 results correlated with patient reported skin involvement (DLQI: -0.25, patient assessment skin: -0.17), and the composite scores DAPSA (-0.33) and DAS28 (-0.28) as well as with patient reported pain (-0.43) and patient global disease assessment (-0.42). The highest correlation was found for physician assessed global health status (-0.51) and PSAID (-0.62). No significant correlation was found with CRP, swollen joint count and physician assessed skin involvement including body surface area (BSA).Table 1.Baseline characteristics of patients included in the analysis stratified by WHO-5 categories.ParameterWHO-5 (N=73WHO-5 (13-28) moderateN=203WHO-5 (29-50) mildN=249WHO-5 (>50) well-beingN=411TotalN=936Age, mean (SD)52.6 (11.4)51 (11.3)51.4 (12.5)52.8 (12.7)52 (12.2)Female, n (%)52 (71.2)127 (62.6)157 (63.1)227 (55.2)563 (60.1)Disease duration, years, mean (SD)8.3 (8.7)6 (7.9)6.2 (6.7)6.4 (7.5)6.4 (7.5)Dactylitis, n (%)14 (19.7)31 (15.5)46 (18.5)77 (18.8)168 (18.1)Axial involvement, n (%)14 (19.7)54 (26.9)49 (19.7)71 (17.3)188 (20.2)Nail involvement, n (%)34 (47.2)85 (42.3)106 (42.6)158 (38.6)383 (41.1)BMI>=30, n (%)37 (51.4)75 (37.1)98 (39.5)125 (30.9)335 (36.2)CRP of >=5 mg/L, n (%)33 (51.6)84 (45.4)99 (46.5)138 (39.1)354 (43.4)BSA (0-100), mean (SD)10.1 (18.3)9.5 (16.8)8.5 (14.9)8.1 (14.6)8.7 (15.5)Physician assessed global health (NRS 0-10), mean (SD)6.3 (1.5)5.6 (1.8)5.2 (1.7)4.9 (1.9)5.2 (1.9)TJC68, mean (SD)9.9 (7.1)8.6 (7.6)8.2 (7.6)7.3 (8.2)8 (7.8)SJC66, mean (SD)6 (5.2)4.8 (4.9)4.7 (4.4)4.3 (3.8)4.6 (4.4)DAPSA, mean (SD)29.3 (11.1)25.1 (12.9)23.4 (12.1)18.9 (12.4)22.3 (12.8)DAS28-CRP, mean (SD)4.1 (1)3.8 (1.2)3.7 (1.1)3.2 (1.1)3.6 (1.2)Patient assessed global health (NRS 0-10), mean (SD)7.9 (2.1)6.6 (2.1)5.9 (2)4.8 (2.3)5.7 (2.4)Patient assessed pain (NRS 0-10), mean (SD)7.8 (1.8)6.4 (2.1)5.8 (2)4.6 (2.4)5.5 (2.4)DLQI (0-30), mean (SD)8.5 (8.2)7.8 (7.2)5.4 (5.7)4.1 (4.9)5.6 (6.2)PSAID (0-10), mean (SD)6.9 (1.8)5.5 (1.8)4.4 (1.7)3 (1.7)4.2 (2.2)Conclusion:The impact of depressive symptoms on outcome parameters used in rheumatology is increasingly being recognised. Interestingly, direct measures of inflammatory disease activity of joint and skin disease such as BSA, CRP, and swollen joint count were not correlated with depressive symptoms. The highest correlation was found for broader assessments like global health status and PSAID.References:[1]Haugeberg et al. Arthritis research & Therapy, 2020, 22:198Acknowledgements:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.We thank all participating rheumatologists and patients.Disclosure of Interests:Anne Regierer Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Anja Weiß Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Martin Bohl-Buehler: None declared, Xenofon Baraliakos: None declared, Frank Behrens: None declared, Georg Schett: None declared, Anja Strangfeld Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.

Background:Disease flares in axial spondyloarthritis (axSpA) might occur even in patients with otherwise stable disease receiving highly effective anti-inflammatory therapy such as TNF inhibitors. The frequency of disease flares, especially in patients with axSpA receiving long-term stable therapy, and factors associated with flares are not sufficiently investigated.Objectives:The objective was to assess the frequency of disease flares and to identify factors associated with flares in patients with early axSpA receiving continuous long-tem (up to 10 years) treatment with a TNF inhibitor etanercept.Methods:In the ESTHER (etanercept versus sulfasalazine in early axial spondyloarthritis trial), patients with early axSpA (symptom duration ≤5 years) were treated with ETN (n=40) versus sulfasalazine (n=36) for 48 weeks [2]. After one year all patients were treated continuously with etanercept (n=17 patients temporarily interrupted treatment in the 2nd year to assess time to flare and were then (re-)treated with etanercept, except 4 patients who completed the study in sustained remission) for up to 10 years in total. Only patients who were continuously treated with etanercept for at least 6 months were included in the current analysis. The disease flare was defined as a worsening of the ASDAS by ≥0.9 as compared to the value obtained at the previous visit. Univariate and multivariable cox-regression analyses were performed to analyze the predictors of flares.Results:Out of 76 patients who entered the study at baseline, 62 patients (n=32 with radiographic (r-) axSpA and n=30 with non-radiographic (nr-) axSpA) fulfilled the criterion of the continuous etanercept treatment. A total of 22 patients (35%) experienced at least one flare over the entire treatment period 10 patients (31.3%) in the r-axSpA and 12 patients (40%) in the nr-axSpA subgroup) - figure. A total of 81 flares occurred (33 and 48 in the r- and nr-axSpA subgroups, respectively) in the 10 years of follow-up. None of the documented disease flares resulted in a direct study withdrawal. The majority of flares occurred within first 4 years of treatment (figure). There were also no statistically significant differences between nr- and r-axSpA in the time until the first flare (p=0.4, Log-rank test). In the multivariable Cox regression analysis normal CRP values (≤5mg/l), HLA-B27 negativity, higher physician global assessment, a longer symptom duration at study entry, higher spinal ankylosis and higher fatty degeneration in the sacroiliac joints but lower spinal osteitis scores and lower ankylosis scores in the sacroiliac joints at baseline MRI were associated with a higher risk for flares.Conclusion:Disease flares according to the ASAS definition of clinically important worsening in axSpA based on ASDAS occurred ~1/3 of patients with early axSpA who received a treatment with etanercept for up to 10 years without major differences between r- and nr- forms of axSpA. HLA-B27 negativity, normal CRP, higher spinal ankylosis scores, higher fatty degeneration scores but lower ankylosis scores in the SIJ´s at baseline MRI were associated with a higher risk for flares.Figure 1.Baseline characteristics of all patients with with continous ETC treatment.all≥1 flareno flarepatientsn (%)62 (100)22 (35.5)40 (64.5)malen (%)38 (61.3)16 (72.7)22 (55)agemean (SD)34.1 (8.3)32.6 (7.8)35 (8.6)BASDAImean (SD)2.7 (2)1.8 (1.8)3.2 (1.9)ASDASmean (SD)1.6 (0.8)1.3 (0.7)1.7 (0.8)Figure 2.Kaplan-Meier curves indicating time to first flare and flare free survival propability.Acknowledgments:The ESTHER study was supported by an unrestricted research grant from Pfizer. Murat Torgutalp’s (MT) work at Charité - Universitätsmedizin was supported by an award from the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Murat Torgutalp: None declared, Anja Weiß: None declared, Mikhail Protopopov Consultant of: Novartis, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Kay Hermann: None declared, Christian Althoff: None declared, Olaf Behmer Employee of: Pfizer Pharma GmbH, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

Background Inhibition of interleukin-1 (IL-1) represents a promising treatment option in adult-onset Still’s disease (AOSD). Canakinumab (CAN) is approved for treatment of systemic juvenile idiopathic arthritis (sJIA) since 2013 and recently for AOSD in Europe. In sJIA, CAN has a proven marked impact on systemic and articular disease activity, but for AOSD RCT data is limited. Objectives Investigation of efficacy and safety of CAN in AOSD patients with joint involvement by means of a multi-centre, double-blinded, randomized, placebo controlled trial. Methods AOSD patients with joint involvement (tender and swollen joint count ≥4 each) were stratified by pre-treatment status with biologics and randomized in a ratio of 1:1 to CAN (4 mg/kg up to a maximum of 300 mg) or placebo (PBO) s.c. every 4wks. The primary endpoint was defined as the proportion of patients with a clinical-relevant reduction (≥1.2) in disease activity as measured by change in disease activity score (DAS28) at week 12. There were two major protocol violations: two PBO patients received blinded CAN at week 4. Therefore, a per-protocol (PP) analysis, which excluded data of these two patients, was performed. Results The study was prematurely stopped with 35 out of 68 planned patients enrolled due to approval of CAN for AOSD by EMA. At enrollment, mean DAS28 represented high disease activity for both: 5.4 in CAN (n=18) and 5.3 in PBO (n=17). In the intention-to-treat analysis, 12 (67%) CAN and 7 (41%) PBO patients met the primary endpoint. The 25.5% [95%CI: -10.3%; 55.9%] difference in the response rate did not achieve statistical significance (p=0.18). Using the PP analysis, the treatment difference for primary endpoint was 33.4% [95%CI: -10.3%; 55.9%, p=0.08]. We observed higher ACR50 (50% CAN vs. 6.7% PBO, p= 0.009), ACR70 (28% CAN vs. 0% PBO, p=0.049) response rates, (PP analysis). Higher mean improvements in the CAN vs PBO group for DAS28(ESR and CRP), ESR, CRP, 66 swollen and 68 tender joint counts at week 12 were observed (PP analysis). There were 47 and 21 non-serious adverse events (AE) reported in CAN and PBO groups, respectively. Two CAN patients experienced an SAE (hepatotoxicity and patellofemoral pain syndrome). Conclusion Although the study was terminated prematurely and the primary endpoint did not achieve statistical significance, treatment of patients with active AOSD with CAN led to improvement of several outcome measures. In addition, safety profile was similar to that reported in sJIA and no unexpected safety issues were observed. This data support the treatment of AOSD patients with CAN. References [1] Ruperto. NEJM (2012): 2396-2406 Disclosure of Interests Claudia Kedor Grant/research support from: Sobi, Consultant for: Novartis, Speakers bureau: Novartis, Roche, Joachim Listing: None declared, Jan Zernicke: None declared, Anja Weis: None declared, Frank Behrens Grant/research support from: AbbVie, Pfizer, Roche, Chugai, Prophylix, Bioline, Novartis, Consultant for: AbbVie, Pfizer, Roche, Chugai, UCB, Bristol-Myers Squibb, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Eli Lilly, Speakers bureau: Ad board: AbbVie, Pfizer, Roche, Chugai, UCB, Bristol-Myers Squibb, Celgene, Novartis, Biotest, Janssen, Genzyme, Eli Lilly, Norbert Blank Grant/research support from: SOBI and Novartis, Speakers bureau: Novartis and SOBI, Jorg Henes: None declared, Jorn Kekow: None declared, Andrea Rubbert-Roth Consultant for: Chugai, Eli Lilly, Roche, and Sanofi , Speakers bureau: AbbVie, Bristol-Myers Squibb, Chugai, Hexal/Novartis, Janssen, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, and Sanofi , Hendrik Schulze-Koops Grant/research support from: Novartis, Pfizer, Roche, Consultant for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Paid instructor for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Speakers bureau: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Eva Seipelt: None declared, Christof Specker: None declared, Eugen Feist Grant/research support from: Pfizer, Roche, Novartis, BMS, Sanofi, Lilly, Consultant for: Pfizer, Roche, Novartis, BMS, Abbvie, Celgene, Sanofi, MSD, Lilly, Speakers bureau: Pfizer, Roche, Novartis, BMS, Abbvie, Celgene, Sanofi, Lilly

Background: Inhibition of interleukin-1 (IL-1) represents a promising treatment option in adult-onset Still's disease (AOSD). Canakinumab is approved for treatment of systemic juvenile idiopathic arthritis and has a marked impact on systemic as well as articular activity of the disease. Objective: To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multi-centre, double-blinded, randomized, placebo controlled trial. Methods: Patients with AOSD and active joint involvement (tender and swollen joint count ≥4 each) were stratified by pre-treatment status with biologic DMARDs to canakinumab (4 mg/kg, maximum 300 mg s.c. q4w) or placebo. After approval of canakinumab for AOSD by the European Medicines Agency, recruitment was stopped prematurely with enrollment of 35 out of 68 planned patients. The primary endpoint was the proportion of patients with a clinically-relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28 >1·2). Results: At enrollment, patients had high active disease with a mean DAS28(ESR) of 5·4 in the canakinumab group (n=18, [CI 43·1 ; 85·2]) and 5·3 in the placebo group (n=17, [CI 20·1 ; 65·0]). In the intention-to-treat analysis, 12 (67%) canakinumab and 7 (41%) placebo patients fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher ACR30 (61% vs. 33% p=0.033), ACR50 (50% vs. 6·7% p= 0.009) and ACR70 (28% vs. 0% p=0·049) response rates were observed in the canakinumab group compared with placebo. Two patients in the canakinumab group experienced an SAE. Conclusion: Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD. Trial Registration: EudraCT No. 2011-001027-20. Funding Statement: Novartis Pharma GmbH Deutschland for financial support and study drug provision. Declaration of Interests: CK has received personal advisory board and congress fees from Novartis, Pfizer, Roche, and Sobi. FB has received grants from Abbvie, Pfizer, Roche, Chugai, Janssen and consultant, speaker, or advisory board fees from Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; and Sandoz. NB has received grants from Novartis and Sobi, and personal fees from Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, and Roche. JH has received grants from Novartis, Roche, Celgene, and advisory board and speaker fees from Novartis, Roche, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim, and Celgene. ARR has received speaker fees from UCB, and advisory board and speaker fees from Novartis, Roche, Lilly, Pfizer, Abbvie, BMS, Janssen, Sanofi, and Celgene. CS has received personal fess from Abbvie, BoehringerIngelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB, and Toshiba. EF has received advisory board and speaker fees from Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, and Sanofi. The remaining authors declare no competing interests. Ethics Approval Statement: The study was conducted according to the ethical principles of the Declaration of Helsinki. The study protocol and all amendments were reviewed by the Independent Ethics Commission of the State of Berlin (Ethik-Kommission des Landes Berlin) and Independent Ethics Committees for each center (EudraCT No. 2011-001027-20, Protocol No.: CACZ885GDE01T, ethic No 11/0561 – ZS EK 11). All patients provided written informed consent before any assessment was performed.

This article offers a sociological approach to the ongoing debate about the distinction between refugees and migrants. It adopts a life-course perspective on seeking refuge. Seeking refuge is embedded not only in the legal regimes of refugee protection, but also in other institutional frameworks governing the life-course. Exploring continuities between migrants and refugees allows for a better understanding of whether and under what preconditions the refugee category is applied by administrations and accessed by refugees themselves. With the help of case studies selected strategically from a larger sample of narrative interviews with university educated migrants to Germany, Turkey, and Canada, the article shows how the implementation and administration of the Geneva Refugee Convention in Germany is organized in a manner that often diverges from the empirical reality of fleeing from persecution and lack of protection. On this basis, a broader comparison with migrants in Turkey and Canada who could fall under the Geneva Refugee Convention, but who mostly refrain from claiming asylum, shows that those with better resources and socio-spatial autonomy can, if well informed, find alternative options for gaining protection rather than claiming refugee status. Whether migrants under duress see themselves as refugees and whether they claim asylum does not only result from the persecution they face but also from specificities of legal and administrative frameworks, as well as their position in global structural inequalities and it is related to divergent degrees of socio-spatial autonomy. Resumen Este artículo presenta un enfoque sociológico para el debate en curso sobre la distinción entre refugiados y migrantes. Para ello, yo adopto enfoque de curso de vida para el análisis de la búsqueda de refugio. La búsqueda de refugio está incorporada no sólo en los regímenes legales de protección a los refugiados, sino también en otras estructuras institucionales que dirigen el curso de la vida. Explorar las continuidades entre migrantes y refugiados permite una mejor comprensión de si, y bajo qué requisitos previos la categoría de refugiado es aplicada por las autoridades y accedida por los propios refugiados. Haciendo uso de estudios de caso elegidos estratégicamente a partir de una muestra mayor de entrevistas narrativas con migrantes con formación académica, en Alemania, Turquía y Canadá, el artículo muestra cómo la implementación y la administración de la Convención de Ginebra sobre los refugiados en Alemania se organiza de una forma que muchas veces se aleja de la realidad empírica de la fuga por persecución y por falta de protección. A partir de ello, se hace una comparación más amplia, con migrantes en Turquía y Canadá que podrían encuadrarse en la Convención de Ginebra sobre los refugiados, pero que, en su mayor parte, se abstienen de reivindicar asilo. Se ha observado que aquellos con mejores recursos y autonomía socio-espacial pueden, si están bien informados, encontrar alternativas para ganar protección, en lugar de reclamar el estatus de refugiado. Si los migrantes bajo coacción se ven a sí mismos como refugiados y si reclaman asilo o no es resultado no solo de la persecución que enfrentan, sino también de las especificidades de los marcos legales y administrativos, así como su posición en las desigualdades estructurales globales y, además, tiene relación con los distintos grados de autonomía socio-espacial. Resumo Este artigo apresenta uma abordagem sociológica para o debate em curso sobre a distinção entre refugiados e migrantes. Para tanto, adoto uma perspectiva de trajetória de vida para a análise da busca de refúgio. Esta busca por refúgio está incorporada não apenas nos regimes legais de proteção aos refugiados, mas também em outras estruturas institucionais que regem o curso da vida. Explorar as continuidades entre migrantes e refugiados permite uma melhor compreensão de se, e sob quais pré-requisitos, a categoria refugiado é aplicada pelas autoridades e acessada pelos próprios refugiados. Com a ajuda de estudos de caso estrategicamente selecionados a partir de uma amostra maior de entrevistas narrativas com migrantes com formação acadêmica, na Alemanha, Turquia e Canadá, o artigo mostra como a implementação e a administração da Convenção de Genebra sobre Refugiados na Alemanha é organizada de forma muitas vezes distanciada da realidade empírica da fuga por perseguição e falta de proteção. Com base nisso, uma comparação mais ampla, com migrantes na Turquia e no Canadá que poderiam se enquadrar na Convenção de Genebra sobre Refugiados, mas que, na sua maior parte, se abstêm de reivindicar asilo, mostra que aqueles com melhores recursos e autonomia socioespacial podem, se bem informados, encontrar opções alternativas para ganhar proteção ao invés de reivindicar o status de refugiado. Ver-se como refugiado ao migrar sob coação e reivindicar ou não asilo não resulta exclusivamente da perseguição enfrentada, mas também das especificidades dos marcos legais e administrativos, bem como da posição que a pessoa ocupa nas desigualdades estruturais globais, e tem relação com os diferentes graus de autonomia socioespacial.

Objective.To compare clinical examination versus whole-body magnetic resonance imaging (WB-MRI) of enthesitis in patients with early axial spondyloarthritis during 3 years of continuous etanercept (ETN) treatment.Methods.Forty-one patients underwent clinical and WB-MRI examinations for enthesitis at baseline and after 2 and 3 years of treatment. Twenty-one sites were assessed in 4 anatomic regions — anterior chest wall, pelvis, knee, and foot.Results.Clinical examination at baseline detected enthesitis in 57% of the patients (85 lesions, mean 2.1 lesions, SD 2.9), most of them in the pelvis (42 lesions in 17 patients) and anterior chest wall (19 lesions in 10 patients). The proportion of patients with clinically detected enthesitis decreased to 19% at Year 2 (mean 0.5, SD 1.5) and 14% at Year 3 (mean 0.7, SD 1.8). WB-MRI detected enthesitis at baseline in 21% of patients (22 lesions, mean 0.5 lesions, SD 1.1), also most frequently in the pelvis (12 lesions) and anterior chest wall (7 lesions). MRI-positive enthesitis decreased to 13% at Year 2 (mean 0.2 lesions, SD 0.5) and 14% at Year 3 (mean 0.2 lesions, SD 0.5). There was positive correlation of clinical and MRI findings at baseline at the anterior chest wall (p = 0.001) and the pelvis (p = 0.0001). No correlation was found at the knee and foot at baseline and for all regions at followup.Conclusion.Both clinical examination and WB-MRI show a decrease in enthesitis after 2 and 3 years of ETN treatment, but correlation was limited to the pelvis and anterior chest wall at baseline.

Objective To assess the relationship between active inflammation and development of chronic lesions in the spine and sacroiliac (SI)-joints on MRI in early axial spondyloarthritis (SpA) during treatment with etanercept. Methods Here, we analyzed the 41 patients of the ESTHER trial, who were treated with etanercept over 3 continuous years and of whom MRIs were available for baseline, year 2, and year 3. MRIs were scored for active inflammation (STIR sequences) and chronic changes (T1 sequence) such as fatty lesions, erosions, and ankylosis in the SI joints and spinal vertebral units (VUs). Results The mean fatty lesion scores increased between baseline and year 2 both in the spine (1.13 at baseline vs. 1.40 at year 2, p = 0.0254) and in the SI joints (4.76 at baseline vs. 5.46 at year 2, p = 0.27), but we found no further increase of the fatty lesion score between years 2 and 3. New fatty lesions at years 2 and 3 developed nearly exclusively in SI joint quadrants and VUs in which active MRI inflammation was present at baseline. Fatty lesions disappeared only in 3 SI joint quadrants and in none of VUs at years 2 and 3. Erosion and ankylosis scores remained unchanged. Conclusion Our data indicate a relationship between the presence of active MRI inflammation and the new development of fatty lesions. Furthermore, there was no increase of fatty lesions during continuous treatment of axial SpA patients with etanercept after successful suppression of active inflammation. Whether this is predictive of stopping radiographic progression needs to be further investigated. Significance and Innovations •This is the first study prospectively following inflammatory lesions, including fatty lesions on MRI of spine and sacroiliac joints of patients with early axial SpA treated over 3 years of continuous treatment with a TNF-inhibitor. •No further increase of fatty lesions between year 2 and year 3 was found in early axial SpA patients treated continuously with etanercept. •Our data indicate a strong relationship between the presence of active MRI inflammation and the new development of fatty lesions. •Whether this is predictive of stopping radiographic progression needs to be further investigated.

Background:Long-term data on anti-TNF treatment in patients with early axial spondyloarthritis (SpA) is scarce.Objectives:The objective of this analysis was to assess the long-term clinical efficacy (up to 10 years of treatment) of a tumor necrosis factor (TNF) inhibitor etanercept (ETN) in patients with early axial spondyloarthritis, who participated in the long-term (until year 10) extension of the ESTHER (Etanercept vs. Sulfasalazine in Early Axial Spondyloarthritis Trial) trial.Methods:In the previously reported ESTHER trial, patients with early active axial SpA [including both non-radiographic axial SpA (nr-axSpA) and radiographic axial SpA (r-axSpA)/ankylosing spondylitis (AS)] with a symptom duration of Results:Out of 76 initial patients, 25% (n=19, 12 with r-axSpA and 7 with nr-axSpA) completed year 10 of the study. At baseline, completers were significantly more often male and showed lower values of patient (PGA) and physician global assessments of disease activity (PhGA), ASDAS (Ankylosing Spondylitis Disease Activity Score), BASMI (Bath Ankylosing Spondylitis Metrology Index), and AS-QoL (Ankylosing Spondylitis Quality of Life Questionnaire) as compared to non-completers (Table 1). When analyzing clinical data of the completers, mean BASDAI, BASFI and ASDAS values were constantly Conclusion:A sustained clinical response was shown over the 10 years of the study for the completers with comparable rates between r-axSpA and nr-axSpA. ETN was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals.Table 1.Baseline characteristics of patients with axial spondyloarthritis who completed the study as compared to patients who dropped out.Completer(n=19)Non-Completer(n=57)p valueAge, years32.5 (7.4)32.8 (8.9)0.91Male patients, n (%)15 (78.9)29 (50.9)0.034Symptomduration, years1.1 (1.2)1 (1.7)0.81HLA-B27 positivity, n (%)18 (94.7)44 (77.2)0.091Elevated CRP (CRP>5mg/l), n (%)7 (38.9)33 (62.3)0.088Fulfilled New York criteria, n (%)12 (63.2)27 (47.4)0.24Patient global (0-10)6.1 (1.9)7.2 (1.7)0.025Physician global (0-10)5.5 (1.5)6.5 (1.2)0.007ASDAS3 (0.7)3.5 (0.8)0.042BASDAI (0-10)5.4 (1.1)5.8 (1.3)0.27BASFI (0-10)4 (2.1)4.4 (2)0.41BASMI (0-10)1.2 (1.3)2 (1.6)0.039AS-QoL (0-18)7.6 (3.9)10.1 (3.9)0.019Acknowledgments:The ESTHER study was supported by an unrestricted research grant from Pfizer.Murat Torgutalp’s work at Charité was supported by an award from the Scientific and Technological Research Council of Turkey.Disclosure of Interests:Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Murat Torgutalp: None declared, Anja Weiß: None declared, Mikhail Protopopov Consultant of: Novartis, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Olaf Behmer Employee of: Pfizer Pharma GmbH, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

Background:Axial spondyloarthritis (axSpA) is a potentially severe chronic inflammatory disease with impact on function and quality of life. About 20-30% of axSpA patients show symptoms of depression or are diagnosed with depression [1]. Depression may influence outcome, especially patient reported outcomes.Objectives:To assess differences in baseline characteristics and outcome parameters between patients with and without symptoms of depression using WHO-5 score.Methods:RABBIT-SpA is a prospective longitudinal cohort study including axSpA patients enrolled at start of a new conventional treatment (including NSAID) or bDMARD. WHO-5 score was used to identify depressive symptoms categorised into 3 groups using validated cut-offs: moderate to severe depressive symptoms 50. Baseline values of patients categorised as having moderate to severe depressive symptoms were compared with the rest of the patients using t-test. Spearman correlation coefficient was calculated to analyse the relationship between WHO-5 score and other outcome parameters.Results:A total of 848 axSpA patients were included in this analysis (table 1). Moderate to severe depressive symptoms were found in 221 patients (30%), 226 (31%) had mild depressive symptoms and 285 (39%) reported a good well-being. Percentages of patients with inflammatory back pain, peripheral arthritis or enthesitis as well as the number of affected joints (44 JC) and entheseal sites (using SPARCC) were higher in the group of patients with moderate to severe depressive symptoms.Table 1.ParameterWHO-5 (Moderate severeN=221WHO-5 (29-50/>50)Mild/well-beingN=511Age, mean43.844.1Female, n (%)100 (45.2)229 (44.8)Disease duration, years, mean6.86.5Inflammatory back pain, n (%)195 (88.6)416 (81.6)Enthesitis, n (%)49 (22.3)78 (15.4)Peripheral arthritis (44 JC), n (%)64 (29.1)134 (26.3)Uveitis, n (%)45 (20.4)76 (15)IBD, n (%)13 (5.9)31 (6.1)Psoriasis, n (%)35 (15.8)58 (11.4)CRP positive (≥5mg/l), n (%)115 (59)243 (55.1)HLA-B27, n (%)151 (72.6)354 (74.2)BMI≥30, n (%)66 (30)117 (23.6)Comorbidities ≥3, n (%)50 (22.6)89 (17.4)Current smoking, n (%)102 (47.2)185 (36.7)All analysed outcome parameters (e.g. ASDAS, ASAS-HI, BASDAI, BASFI, patient global, physician global, pain, sleep) were significantly worse in the group of patients with moderate to severe depressive symptoms versus the other patients (table 2). This includes physician-reported, patient-reported and composite scores.Table 2.ParameterWHO-5 (Moderate severeN=221WHO-5 (29-50/>50)Mild/well-beingN=511p-valuePhysGA (NRS 0-10)6.2 (1.6)5.4 (1.9)0.0001ASDAS6.1 (1.6)4.2 (1.8)0.0001BASDAI (NRS 0-10)3.5 (0.8)2.9 (0.9)0.0001BASFI (NRS 0-10)5.5 (2.2)3.2 (2.2)0.0001ASAS-HI (0-17)9.8 (3.1)5.8 (3.1)0.0001PatGA (NRS 0-10)7 (1.8)5.4 (2.3)0.0001PatPain (NRS 0-10)6.9 (1.9)5.2 (2.3)0.0001PatSleep (NRS 0-10)7.2 (2.4)4.6 (2.9)0.0001Results are presented as mean ± SD.WHO-5 was highly correlated with all outcome parameters regardless of gender. Figure 1 shows the correlation of BASDAI and WHO-5 stratified for gender.Figure 1.Conclusion:Almost one third (30%) of axSpA patients in this analysis reported scores indicative of depressive symptoms and depression. The strong correlation of WHO-5 scores with patient and physician reported outcomes may be relevant for the management of patients with axSpA.References:[1]Redeker I, et al. Ann Rheum Dis 2018;0:1–8. doi:10.1136Acknowledgments:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Janssen-Cilag, Lilly, MSD, Mylan, Novartis, Pfizer, and UCB.Disclosure of Interests:Anne Regierer Speakers bureau: Novartis, Celgene, Janssen-Cilag, Anja Weiß: None declared, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Ilka Schwarze: None declared, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Angela Zink Speakers bureau: AbbVie, Amgen, BMS, Gilead, Hexal, Janssen, Lilly, MSD, Pfizer, Roche, Sanofi Aventis, UCB, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis

Background:Inhibition of interleukin-1 (IL-1) represents a promising treatment option in adult-onset Still’s disease (AOSD). Canakinumab is approved for treatment of systemic juvenile idiopathic arthritis and has a marked impact on systemic as well as articular activity of the disease.Objectives:To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multi-centre, double-blinded, randomized, placebo controlled trial over a period of 24 weeks with the option of a long-term extension.Methods:Patients with AOSD and active joint involvement (tender and swollen joint count ≥4 each) were stratified by pre-treatment status with biologic DMARDs to canakinumab (4 mg/kg, maximum 300 mg s.c. q4w) or placebo. After approval of canakinumab for AOSD by the European Medicines Agency, recruitment was stopped prematurely with enrollment of 35 out of 68 planned patients. The primary endpoint was the proportion of patients with a clinically-relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28 >1.2).Results:At enrollment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab group (n=18, [CI 43.1; 85.2]) and 5·3 in the placebo group (n=17, [CI 20.1; 65.0]). In the intention-to-treat analysis, 12 (67%) canakinumab and 7 (41%) placebo patients fulfilled the primary outcome criterion (p=0.18). Figure 2 shows the DAS28-ESR disease activity by treatment groups and visits with imputation. In the per-protocol analysis, significantly higher ACR30 (61% vs. 33% p=0.033), ACR50 (50% vs. 6.7% p= 0.009) and ACR70 (28% vs. 0% p=0.049) response rates were observed in the canakinumab group compared with placebo (Figure 1). Two patients in the canakinumab group experienced an SAE.Figure 1.Response rates (PP)Figure 2.DAS28-ESR disease activity by treatment groups and visits with imputationConclusion:Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.References:[1]Nirmala N et al. Gene-expression analysis of AOSD and SJIA is consistent with a continuum of a single disease entity. Pediatr Rheumatol Online J. 2015P-values are shown above each pair of bars; P-values in red are significant ACR, American College of Rheumatology; CRP, C-reactive protein; DAS, disease activity score; EULAR, European League Against Rheumatism; PP, per-protocolDisclosure of Interests:Claudia Kedor Consultant of: Advisory Board for Novartis Pharma GmbH, Joachim Listing: None declared, Jan Zernicke: None declared, Anja Weiß: None declared, 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, Norbert Blank Grant/research support from: Novartis, Sobi, Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,, Jörn Kekow Speakers bureau: BMS, MSD, Pfizer, Roche, Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc, Eva Seipelt: None declared, Christof Specker Consultant of: Abbvie, Boehringer Ingelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB, Toshiba, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi

Background:PsA is a complex disease characterised by a heterogeneous pattern including different clinical symptoms of musculoskeletal (MSK) inflammation like arthritis, enthesitis, dactylitis and axial involvement as well as skin and nail involvement. There are differences in these disease patterns between female and male patients which need to be taken into account.Objectives:To assess the differences between female and male PsA patients in the extent of psoriatic skin (body surface area, BSA) and joint (tender joint count 68, TJC68; swollen joint count 66, SJC66;) disease, composite scores (disease activity in PsA, DAPSA; disease activity score 28, DAS28), and patient-reported outcomes (PROs) and to correlate the extent of skin disease with PROs.Methods:RABBIT-SpA is a prospective longitudinal cohort study including PsA patients enrolled at start of a new csDMARD, bDMARD or tsDMARD. Gender specific differences in outcome parameters are compared using Wilcoxon resp. t-test at baseline visit. Spearman correlation coefficient was calculated to analyse the relationship between BSA and outcome parameters.Results:722 PsA patients were included in this analysis. Women were slightly older (52 vs 50 yrs), had longer disease duration (7 vs 5.8 yrs), more comorbidities and were more often obese. Men had a significantly higher skin involvement than women measured by BSA and physician skin assessment (physSk, table 1). Women had significantly higher joint involvement as measured by TJC68, DAPSA, DAS28, and patient muskuloskeletal assessment (patMSK). Impact of disease as measured by PSAID and patient global assessment (patGA) was more severe in women than in men and also physical function (HAQ) was lower in women than in men (table 1). Despite the higher skin involvement in men, the DLQI was equally high in women and men with more than 50% of patients in reduced quality of life state (table 1).Table 1.ParameterFemaleN=424MaleN=298SJC663.4 (5)2.7 (3.8)TJC687.9 (8.7)5.7 (7)BSA (0-100)6.6 (13)10.8 (16.5)physGA (NRS 0-10)5.3 (1.9)5.2 (2)physSk (NRS 0-10)3.1 (2.7)3.7 (2.6)physMSK (NRS 0-10)5.2 (2.1)4.9 (2.3)DAPSA24.2 (13.8)20.1 (12.3)DAS28-CRP3.7 (1.2)3.4 (1.2)patGA (NRS 0-10)5.5 (2.1)4.9 (2)patSk (NRS 0-10)3.9 (3.1)3.9 (2.8)patMSK (NRS 0-10)5.8 (2.2)5 (2.5)DLQI (0-30)6.1 (6.8)5.3 (5.7)HAQ (0-3)1.1 (0.6)0.7 (0.6)PSAID (0-10)4.8 (2.3)3.9 (2.2)Results are presented as mean ± SD.BSA was not correlated with SJC66 or TJC68, DAPSA, DAS28, phys MSK, patGA and patMSK neither in men nor in women. BSA was however positive correlated with DLQI, patSk, and physSK and slightly with physGA in both genders. The PSAID is correlated to BSA in women only.Conclusion:Women and men show differences regarding many PsA criteria. Men have a more severe skin involvement, while women have higher burden of joint involvement. In addition in the patient reported parameters women show significantly higher values than men except for the skin specific parameters. Notably, although skin involvement is not correlated with most PsA activity parameters, around 50% of patients in specialised rheumatologic care are negatively affected in their quality of life by psoriatic skin disease. Therapeutic decisions need to take into account the complexity of the patients’ symptoms as well as gender differences.Acknowledgments:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Janssen-Cilag, Lilly, MSD, Mylan, Novartis, Pfizer, and UCB.Disclosure of Interests:Anne Regierer Speakers bureau: Novartis, Celgene, Janssen-Cilag, Anja Weiß: None declared, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Martin Feuchtenberger Consultant of: Abbvie, BMS, Chugai, Sanofi, Speakers bureau: Abbvie, BMS, Celgene, Chugai, Jansen-Cilag, Lilly, Pfizer, Roche, Sanofi, UCB, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Angela Zink Speakers bureau: AbbVie, Amgen, BMS, Gilead, Hexal, Janssen, Lilly, MSD, Pfizer, Roche, Sanofi Aventis, UCB, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis

Bis in die 1990er‐Jahre erschienen nationalstaatlich verankerte Institutionen, wie Bildungssystem, Wohlfahrtsstaat und industrielle Beziehungen, so zentral fur Arbeit und Arbeitsmarkte, dass deren grenzuberschreitende Dimensionen kaum erforscht wurden. Neue Impulse fur die wissenschaftliche Auseinandersetzung mit verschiedenen Formen der Transnationalisierung der Arbeit kamen in den letzten Jahrzehnten aus soziologischen Teildisziplinen wie der Migrationsforschung, Studien zu multinationalen Unternehmen und der Institutionenanalyse. Der vorliegende Beitrag pladiert fur eine multi‐perspektivische Analyse, die drei Perspektiven auf die Transnationalisierung von Arbeit starker integriert: (1) die grenzuberschreitende Mobilitat von Arbeitskraften im transnationalen und transregionalen Raum, (2) die grenzuberschreitende Mobilitat von Arbeitstatigkeiten und Wissen, die teilweise, aber nicht zwangslaufig mit einer Verlagerung der Produktionsstandorte verbunden ist, und (3) die Herausbildung europaischer, transnationaler und globaler Institutionen, in welche die grenzuberschreitende Mobilitat von Arbeitskraften, Arbeitstatigkeiten und Wissen zunehmend eingebettet ist. Durch eine solche multi‐perspektivische Analyse von Phanomenen, die sachlich miteinander verknupft sind, aber bislang getrennt voneinander in verschiedenen Teildisziplinen erforscht wurden, lassen sich Synergien herstellen, aber auch bislang unerforschte „blinde Stellen“ erkennen und ausleuchten.