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ZusammenfassungIm Gebiet der Kinderrheumatologie gab es in den letzten Jahrzehnten immense Fortschritte, die sowohl die Diagnostik, als auch die Therapie nachhaltig verbessert haben. Obwohl erst seit 2003 in Deutschland offiziell als Zusatzbezeichnung anerkannt, stehen heutzutage über 200 Kinder- und Jugendrheumatologen (d. h. 1,4 Kinderrheumatologen pro 100 000 Kinder) für die Erkennung und Behandlung von rheumatischen Erkrankungen bei Kindern und Jugendlichen bundesweit zur Verfügung. Neue Erkenntnisse in der Pathogenese rheumatischer Erkrankungen und die sich stetig weiterentwickelnde genetische Diagnostik haben das rheumatische Krankheitsspektrum und die Behandlungsmöglichkeiten dramatisch erweitert Internationale Forschungsnetzwerke und eine spezielle Gesetzgebung für die Entwicklung von pädiatrischen Medikamenten führten zur Zulassung von zahlreichen neuen Rheumamedikamenten, deren Sicherheit im klinischen Alltag seit der Jahrtausendwende systematisch in Deutschland untersucht wird. Maßnahmen zur Sicherung der Versorgungsqualität wurden implementiert, Standardinstrumente zur Bewertung der Krankheitsaktivität und Krankheitslast aus Patientensicht eingeführt sowie Initiativen zur Verbesserung der Versorgung Betroffener (z. B. die ProKind-Initiative) auf den Weg gebracht. Diese Veränderungen haben die Prognose und Lebensperspektive rheumakranker Kinder und Jugendlicher verbessert, wenngleich noch weiterer Optimierungsbedarf besteht.

Objectives Burden of comorbidities are largely unknown in JIA. From 2000, national and international patient registries were established to monitor biologic treatment, disease activity and adverse events in patients with JIA. The aim of this analysis was to investigate in parallel, for the first time, three of the largest JIA registries in Europe/internationally—UK JIA Biologic Registers (BCRD/BSPAR-ETN), German biologic registers (BiKeR/JuMBO), multinational Pharmachild—to quantify the occurrence of selected comorbidities in patients with JIA. Methods Information on which data the registers collect were compared. Patient characteristics and levels of comorbidity were presented, focussing on four key conditions: uveitis, MAS, varicella, and history of tuberculosis. Incidence rates of these on MTX/biologic therapy were determined. Results 8066 patients were registered into the three JIA registers with similar history of the four comorbidities across the studies; however, varicella vaccination coverage was higher in Germany (56%) vs UK/Pharmachild (16%/13%). At final follow-up, prevalence of varicella infection was lower in Germany (15%) vs UK/Pharmachild (37%/50%). Prevalence of TB (0.1–1.8%) and uveitis (15–19%) was similar across all registers. The proportion of systemic-JIA patients who ever had MAS was lower in Germany (6%) vs UK (15%) and Pharmachild (17%). Conclusion This analysis is the first and largest to investigate the occurrence of four important comorbidities in three JIA registries in Europe and the role of anti-rheumatic drugs. Combined, these three registries represent one of the biggest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies.

ZusammenfassungDie interdisziplinäre Forschungskooperation COACH-Konsortium (Chronic Conditions in Adolescents – Implementation and Evaluation of Patient-centered Collaborative Healthcare) untersucht die psychosoziale Situation von Jugendlichen und jungen Erwachsenen mit chronischen körperlichen Erkrankungen. Zur Untersuchung der psychischen Komorbidität wurden bisher 1.023 Patienten mit Diabetes mellitus Typ 1 im Alter von 12–21 Jahren bei Routinevorstellungen in der Klinik bzw. Ambulanz mittels der Screening-Fragebogen Patient Health Questionnaire (PHQ-9) und Generalized Anxiety Disorder Scale-7 (GAD-7) zu Angst- und Depressionssymptomen befragt. 29,8 % der Jugendlichen und jungen Erwachsenen zeigten ein auffälliges Screening-Ergebnis. Dabei wurden 17,8 % der Fragebogen zu Angstsymptomen und 25,6 % der Fragebogen zu Depressionssymptomen auffällig mit Gesamtscore-Werten ≥ 7 in GAD-7 bzw. PHQ-9 beantwortet. Patienten mit erhöhten Depressions- und Angstwerten wiesen im Mittel einen deutlich höheren medianen HbA1c-Wert als Zeichen einer schlechteren Stoffwechseleinstellung auf (8,33 [8,09; 8,56]) als Patienten mit unauffälligem Screening (7,58 [7,48; 7,68]; p

Adolescence and young adulthood represent a vulnerable phase of life, especially for young people with a chronic rheumatic disease. On the one hand, the chronic disease can impair the biopsychosocial development of young people. On the other hand, risk behaviour common in adolescence and young adulthood can negatively influence the course and outcome of the rheumatic disease. In this challenging and future health-determining phase, up to half of the young people with chronic rheumatic diseases temporarily or permanently drop out of specialized care and are therefore particularly at risk of adverse outcomes. To ensure continuity of care and the best possible outcomes for those affected, young people need education, support, and guidance. They must be prepared to be appropriately responsible and capable of managing their own health and well-being as adults. The key principles to be considered in the care of adolescents and young adults with rheumatic diseases and what is known so far about transitional care in rheumatology are presented in this paper.

To examine whether treatment with interleukin (IL)-1-, IL-6-, tumour necrosis factor α (TNFα)-inhibitors or Abatacept is associated with an increased risk of common infections, infections requiring hospitalization (SAE) or opportunistic infections among real-world juvenile idiopathic arthritis (JIA) patients. Furthermore, the influence of other patient-related covariates on the occurrence of infections was investigated. Patients diagnosed with JIA and treated with biologics were selected from the German BIKER registry. Incidence rates (IR) of infections per 100 person years were calculated and compared between the different cohorts. Using multivariate logistic regression, odds ratios with 95% confidence intervals (CI) were determined for the influence of patient-related covariates (age, diagnosis, laboratory data, concomitant medication, JIA activity, comorbidities, and premedication) on the occurrence of infections. 3258 patients entered the analysis. A total of 3654 treatment episodes were distributed among TNFα- (Etanercept, Adalimumab, Golimumab, Infliximab, n = 3044), IL-1- (Anakinra, Canakinumab, n = 105), IL-6- (Tocilizumab, n = 400) and T-cell activation inhibitors (Abatacept, n = 105). 813 (22.2%) patients had at least one infection, 103 (2.8%) patients suffered from an SAE infection. Both common and SAE infections were significantly more frequent in IL-1 (IR 17.3, 95% CI 12.5/24 and IR 4.3, 95% CI 2.3/8.3) and IL-6 cohort (IR 16.7, 95% CI 13.9/20 and IR 2.8, 95% CI 1.8/4.4) compared to TNFα-inhibitor cohort (IR 8.7, 95% CI 8.1/9.4 and IR 1, 95% CI 0.8/1.3). When comparing the influencing factors for various infectious diseases, the use of corticosteroids, younger age, cardiac comorbidities and higher JIA-activity are the most striking risk factors. Relative to TNFα inhibitors and Abatacept, IL-1 and IL-6 inhibitors were associated with an increased risk of common and SAE infections. The influencing covariates identified may be helpful for the choice of a suitable biologic to treat JIA.

Objectives To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). Methods In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or Results Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. Conclusion s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279

OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.

ZusammenfassungJugendliche und junge Erwachsene mit Typ-1-Diabetes sind häufig von komorbiden psychischen Störungen betroffen. Dabei zeigt die Studienlage zur Verbreitung ein heterogenes und inkonsistentes Bild. Diagnose und Behandlung der somatopsychischen Begleiterkrankungen beeinflussen den Behandlungs- und Krankheitsverlauf sowie die Lebensqualität der Betroffenen. Trotzdem wird dies in der klinischen Praxis selten frühzeitig berücksichtigt. Das multizentrische Verbundprojekt COACH verfolgt das Ziel, die Erkennung und Behandlung psychischer Komorbidität für diese Zielgruppe in der bundesweiten Routineversorgung zu optimieren.

Objective To evaluate safety and effectiveness of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (JIA) in the STRIVE registry. Methods STRIVE enrolled patients with polyarticular-course JIA into 2 arms based on treatment with methotrexate (MTX) alone or ADA with/without MTX (ADA +/- MTX). Adverse events (AEs) per 100 patient-years of observation time were analyzed by registry arm. Patients who entered the registry within 4 weeks of starting MTX or ADA +/- MTX, defined as new users, were evaluated for change in disease activity assessed by the 27-joint Juvenile Arthritis Disease Activity Score with the C-reactive protein level (JADAS-27(CRP)). Results At the 7-year cutoff date (June 1, 2016), data from 838 patients were available (MTX arm n = 301, ADA +/- MTX arm n = 537). The most common AEs were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%) in the MTX arm and arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (3.0% each) in the ADA +/- MTX arm. Rates of serious infection were 1.5 events/100 patient-years in the MTX arm and 2.0 events/100 patient-years in the ADA +/- MTX arm. AE and serious AE rates were similar in patients receiving ADA with versus without MTX. No deaths or malignancies were reported. New users in the ADA +/- MTX arm showed a trend toward lower mean JADAS-27(CRP)compared with new users in the MTX arm in the first year of STRIVE. Conclusion The STRIVE registry 7-year interim results support the idea that ADA +/- MTX is well tolerated by most children. Registry median ADA exposure was 2.47 (interquartile range 1.0-3.6) years, with 42% of patients continuing ADA at the 7-year cutoff date.

ZusammenfassungHintergrundZuverlässige Daten zu Verlauf und Therapie von COVID-19 („corona virus disease 2019“) bei Kindern mit rheumatischen Erkrankungen unter Immunsuppression fehlen.Ziel der ArbeitAbbildung individueller Strategien der Mitglieder der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) im Umgang mit COVID-19.MethodikMittels Online-Umfrage wurden im Mai 2020 das Meinungsbild der GKJR-Mitglieder zum Umgang mit DMARDs („disease-modifying anti-rheumatic drugs“) bei COVID-19-Erkrankung sowie die Bereitschaft zum Einsatz spezieller Therapieansätze bei Patienten mit unterschiedlicher Schwere von COVID-19 erhoben.ErgebnisseEs nahmen 71 Kollegen (27,3 % aller befragten ärztlichen Mitglieder) an der Umfrage teil; davon hatten 28,2 % bereits Patienten mit COVID-19 betreut. Über 95 % der Teilnehmer lehnten eine präventive Anpassung der antirheumatischen Therapie im Rahmen der SARS-CoV-2-Pandemie ab. Bei ambulanten Patienten unter Immunsuppression mit nachgewiesener COVID-19-Erkrankung würden mehr als 50 % der Teilnehmer folgende Therapien aussetzen: intravenöse hoch dosierte Steroide, Cyclophosphamid, Anti-CD20-Antikörper, sowie eine BAFF-, CTLA-4-, TNF-α-Blockade. Hingegen würden nichtsteroidale Antiphlogistika, Hydroxychloroquin (HCQ), orale Steroide, Mycophenolat, IL-1-Blockade sowie Immunglobuline (Ig) von >70 % der Kollegen weiter fortgeführt. Bei stationären Patienten mit COVID-19 würden insgesamt 74,6 % der Kollegen eine COVID-19-gerichtete Therapie erwägen. Bei stabilem Verlauf unter O2-Therapie (Stufe I) würden am häufigsten HCQ (18,3 %), Azithromycin (16,9 %) und Ig (9,9 %) in Betracht gezogen. Bei drohendem (Stufe II) bzw. manifestem Zytokinsturm (Stufe III) würden am häufigsten Anakinra (40,8 % bei Stufe II bzw. 46,5 % bei Stufe III), Tocilizumab (26,8 % bzw. 40,8 %), Steroide (25,4 % bzw. 33,8 %) und Remdesivir (29,6 % bzw. 38,0 %) eingesetzt. Von vielen Kollegen wurde betont, dass die Therapiestrategie individuell und der klinischen Situation entsprechend angepasst werden soll.DiskussionDie Ergebnisse der Online-Umfrage sind vor dem Hintergrund einer aktuell in Deutschland niedrigen Prävalenz von COVID-19 zu sehen und spiegeln somit theoretische Überlegungen der Befragten wider. Da Kinder derzeit nicht im Fokus von prospektiven COVID-19-Studien stehen, scheint der kontinuierliche und kritische kollegiale Fachaustausch bei Therapieentscheidungen umso wichtiger zu sein.

Die Behandlung der juvenilen idiopathischen Arthritis (JIA) hat sich in den vergangenen 2 Jahrzehnten u. a. durch die Verfugbarkeit neuer Substanzen entscheidend verandert. Trotz vorhandener Zulassungen, die sich teilweise aus der Behandlung der rheumatoiden Arthritis ableiten, sind zur Einordnung der vorhandenen Evidenz Leitlinien eine wichtige Entscheidungshilfe. Die 2012 publizierte AWMF-Leitlinie zur „Therapie der juvenilen idiopathischen Arthritis“ wurde zwischen 2018 und 2019 in einem mehrstufigen Prozess aktualisiert und als S2k-Leitlinie aktualisiert. Wichtige Prinzipien und Empfehlungen zur medikamentosen und nicht-medikamentosen Therapie der JIA wurden verabschiedet. Im Fokus all dieser Masnahmen bleibt die rasche Entzundungskontrolle, der Remissionserhalt, die Vermeidung von krankheits- und therapiebedingten Folgeschaden sowie die Gewahrleistung einer storungsfreien somatischen und psychosozialen Entwicklung, Lebensqualitat und Teilhabe der betroffenen Kinder und Jugendlichen. The therapy of juvenile idiopathic arthritis (JIA) has undergone significant changes during the past two decades also due to the availability of new biologic substances. Therapy guidelines gathering the available evidence are crucial for clinical decision-making. The current interdisciplinary therapy guideline was updated between 2018 and 2019 in different steps, leading to an updated adoption of recommendations and principles of medical and non-medical therapy of JIA. The main focus and goal of all therapeutical considerations remains a rapid control of inflammation leading to and maintaining remission while avoiding disease or therapy-associated damage. This shall furthermore allow an appropriate somatic and psycho-social development along with an adequate health-related quality of life and participation of children and adolescents with JIA.

Die juvenile idiopathische Arthritis (JIA) ist die haufigste chronisch-entzundliche rheumatische Erkrankung im Kindesalter. Sowohl die mit Schmerzen und Bewegungseinschrankungen einhergehende Erkrankung als auch die meist komplexe, langfristige Therapie sind mit Belastungen fur die Betroffenen bis ins Erwachsenenalter hinein verbunden. Beeintrachtigungen konnen sich auf viele Lebensbereiche auswirken. Eine ganzheitliche Betreuung mit Berucksichtigung der Praferenzen und geauserten Bedarfe der Patienten und ihrer Familien ist entscheidend, um die angestrebten Therapieziele einer Remission und bestmoglichen Lebensqualitat zu erreichen. Da die JIA in einer sehr fruhen Lebensphase beginnt, sind krankheits- und therapiebedingte Langzeitfolgen von erheblicher Bedeutung. Die Zulassung neuer, spezifisch in den Entzundungsprozess eingreifender Substanzen hat die Behandlung der JIA in den letzten Jahren grundlegend verandert. Vor allem eine fruhe effektive Therapie tragt entscheidend zu einer verbesserten Prognose der JIA-Patienten bei. Mittlerweile gehen JIA-Patienten mit guter Alltagsfunktion und Lebensqualitat sowie weniger Folgeschaden und Begleiterkrankungen ins Erwachsenenalter, wenngleich nur ca. die Halfte eine stabile therapiefreie Remission erreicht. Um den notwendigen Wechsel in die Erwachsenenmedizin zu unterstutzen, wurden Transitionsprogramme entwickelt, die die jungen Rheumatiker auf die neue Betreuungsform vorbereiten und Versorgungslucken sowie ungunstige Outcomes verhindern sollen. Nicht zuletzt ist die Erfassung psychischer Faktoren wichtig, um im Bedarfsfall die chronisch Kranken beim Umgang mit ihrer Krankheit und den daraus resultierenden Herausforderungen zu unterstutzen.

Background To analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome. Methods Prospective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis add-on module from the years 2002 to 2016. Cross-sectional data from the years 2002 to 2016 were analyzed. Patients with JIA-associated uveitis and with ANA-positive idiopathic anterior uveitis were included and the disease manifestation investigated in terms of uveitis characteristics and disease course. Results Of the total cohort of 34,458 patients enrolled in the NPRD, including 3551 patients with uveitis, those with detailed uveitis documentation were taken into account: 62 ANA-positive patients with idiopathic anterior uveitis (group 1), 688 patients with initial uveitis diagnosis after JIA onset (group 2), and 61 JIA patients with initial uveitis diagnosis before arthritis onset (group 3). Anterior uveitis was documented in 100%, 94%, and 80% of patients and with insidious onset of uveitis flare in 50%, 70.9%, and 56.1% each in groups 1, 2, and 3, respectively. Use of topical or systemic corticosteroids and conventional synthetic or biological DMARDs did not significantly differ between the patient groups, either at the initial or the 2-year follow-up (2-FU) visits (mean 2 years, each p > 0.05). At 2-FU, uveitis inactivity was achieved in 64.7%, 55.8%, and 61.5% of patients in groups 1, 2, and 3 (p > 0.05). Uveitis-related complications were more frequent at the initial visit and at 2-FU in groups 1 and 3, as compared to group 2. Conclusions ANA-positive idiopathic uveitis and JIA-associated uveitis do not significantly differ concerning clinical course of uveitis, treatment, and response to corticosteroids and DMARDs.

Objective Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long-term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long-term safety with regard to AE of special interest (AESI) was compared between different biologics. Methods Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose. Results A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2-15, and RR 4.7, 95% CI 1.8-12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation. Conclusion Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long-term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.

Objectives Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset JIA (SJIA) from infectious diseases is difficult. Biomarkers are needed that support the diagnostic work-up. The aim of this study was to validate the usefulness of Myeloid-related protein 8/14 (MRP8/14) measurements in the diagnostic work-up of febrile children and to transfer it to clinical practice. Methods Data for 1110 paediatric patients were included and divided into two cohorts: (cohort A) for validation of MRP8/14 test performance with three different testing systems: the experimental ELISA, commercial ELISA and an innovative (point-of-care test) lateral flow immunoassay (LFIA); (cohort B) to validate the diagnostic accuracy with the two latter assays. Results In cohort A (n = 940), MRP8/14 was elevated in SJIA (12 110 ± 2650 ng/ml mean ± 95% CI) compared with other diagnoses (including infections and autoinflammatory diseases; 2980 ± 510 ng/ml) irrespective of fever and anti-inflammatory treatment (P Conclusion MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test.

Objective Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. Methods Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model. Results Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept. Conclusion Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.

Psychische Erkrankungen wie Depression und Angst beginnen haufig im Jugend- und jungen Erwachsenenalter. Heranwachsende mit einer chronischen rheumatischen Erkrankung haben hierfur ein besonderes Risiko. In Untersuchungen zur psychischen Gesundheit gaben in der Regel uber 10 % der Jugendlichen mit juveniler idiopathischer Arthritis (JIA) depressive Symptome an. Die fruhzeitige Erkennung von psychischen Belastungen ist notwendig, um Betroffenen rechtzeitig adaquate Unterstutzung anbieten zu konnen. Geschieht das nicht, werden Moglichkeiten, die Langzeitprognose und Lebensqualitat der Betroffenen zu verbessern, verpasst. Psychische Storungen werden in der klinischen Praxis oft nur am Rande berucksichtigt. Wie gros das Problem unter den bundesweit kinder- und jugendrheumatologisch betreuten Patienten mit JIA ist, wird in diesem Jahr im Rahmen des interdisziplinaren Forschungsverbundes COACH untersucht. Mental disorders such as depression and anxiety often begin in adolescence and young adulthood. Young people with a chronic rheumatic disease are particularly at risk. More than 10 % of young people with juvenile idiopathic arthritis reported depressive symptoms in most mental health studies. Early recognition of mental health problems is necessary in order to be able to support those affected in a timely and adequate manner. If this does not happen, opportunities to improve the long-term prognosis and quality of life of the young people affected are missed. Psychological stress is often only marginally considered in clinical practice. In order to improve this, the interdisciplinary research network COACH will, starting this year, investigate the extent of mental health problems in adolescents and young adults with JIA, who are receiving nationwide paediatric rheumatological care.

Objective To assess the first-year features of patients with chronic nonbacterial osteomyelitis (CNO). Methods Patients with a diagnosis of CNO, disease duration of under 13 months, and first registration in the German National Pediatric Rheumatologic Database (NPRD) between 2009 and 2018 were included in this cross-sectional analysis. Results Of 774 documented patients, 62.8% were female, and all patients had a median age of 11 years. The most affected clinical sites were the tibia (29.7%), pelvis (28.0%), and femur (27.8%). HLA-B27 was positive in 48 of 314 analyzed patients (15.3%). In 406 patients, an X-ray was performed at the first visit; X-ray results showed osteosclerosis/−lysis in 34.0% and hyperostosis in 14.5% of the patients. MRI scans (focal and whole-body scans) were performed in 648 patients, and 81.5% showed a positive TIRM/STIR signal. A total of 84.7% of the patients were administered nonsteroidal anti-inflammatory drugs, 9.6% were administered oral glucocorticoids, 10.8% were administered disease-modifying anti-rheumatic drugs (DMARDs), and 6.1% were administered bisphosphonates. An evaluation of the patient’s questionnaire showed an overall well-being (NRS 0–10) of 2.0. The PedCNO disease “activity” score revealed a 70% improvement in variables in 43% of patients in the initial 1-year follow-up. Copresentation with diagnostic criteria of pediatric enthesitis-related arthritis was rare. Conclusion To our knowledge, the NPRD cohort seemed to be the largest cohort of children and adolescents suffering from CNO worldwide. Most patients were treated effectively with NSAIDs, and only a small group of patients was administered additional medication. The patient-defined measures of disease activity had a moderate impact on patients’ daily lives. Trial registration Not applicable.

Objective To study juvenile idiopathic arthritis (JIA) long-term outcomes in relation to the time of initiation of biologic disease-modifying antirheumatic drug (bDMARD). Methods Outcomes of JIA patients prospectively followed by the Biologika in der Kinderrheumatologie (BiKeR) and Juvenile Arthritis Methotrexate/Biologics Long-Term Observation (JuMBO) registers were analyzed with regard to drug-free remission and inactive disease, functional status and quality of life, and surgery. To analyze the influence of early bDMARD therapy on outcomes, patients were assigned to 3 groups based on the time from symptom onset to bDMARD start (G1: ≤2 years, G2: >2 to ≤5 years, and G3: >5 years). Propensity score-adjusted outcome differences were analyzed by multinomial logistic regression analyses among the groups. Results A total of 701 JIA patients were observed for mean ± SD 9.1 ± 3.7 years. At the last follow-up (disease duration mean ± SD 14.3 ± 6.1 years), 11.7% of patients were in drug-free remission, and 40.0% had inactive disease. More than half of the patients reported no functional limitation, while 5% had undergone arthroplasty, and 3% had eye surgery. At the 10-year time point, patients in G1 (n = 108) were significantly more likely to be in drug-free remission than those patients who began treatment later (G2, n = 199; G3, n = 259), with 18.5%, 10.1%, and 4.9%, respectively. Patients in G1 had significantly lower disease activity (clinical Juvenile Arthritis Disease Activity Score in 10 joints = 4.9), a better overall well-being (18.2% patient global assessment score = 0), and higher functional status (59.2% Health Assessment Questionnaire score = 0), compared to patients in G3 (7.1, 8.4%, and 43.7%, respectively). G1 patients required arthroplasty significantly less frequently than G3 patients and had significantly lower disease activity over time than patients in both G2 and G3. Conclusion Early DMARD treatment is associated with better disease control and outcomes, which supports the concept of a "window of opportunity" for JIA.

Objective.To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ).Methods.Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112;ClinicalTrials.gov,NCT00642460) and pcJIA (n = 188;ClinicalTrials.gov,NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts.Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8–16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3–8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial.Conclusion.Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

Objective Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging. Methods We analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later. Results Two-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months. Conclusion Our data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.

Data on therapy of COVID-19 in immunocompetent and immunosuppressed children are scarce. We aimed to explore management strategies of pediatric rheumatologists. All subscribers to international Pediatric Rheumatology Bulletin Board were invited to take part in an online survey on therapeutic approaches to COVID-19 in healthy children and children with autoimmune/inflammatory diseases (AID). Off-label therapies would be considered by 90.3% of the 93 participating respondents. In stable patients with COVID-19 on oxygen supply (stage I), use of remdesivir (48.3%), azithromycin (26.6%), oral corticosteroids (25.4%) and/or hydroxychloroquine (21.9%) would be recommended. In case of early signs of “cytokine storm” (stage II) or in critically ill patients (stage III) (a) anakinra (79.5% stage II; 83.6% stage III) or tocilizumab (58.0% and 87.0%, respectively); (b) corticosteroids (oral 67.2% stage II, intravenously 81.7% stage III); (c) intravenous immunoglobulins (both stages 56.5%); or (d) remdesivir (both stages 46.7%) were considered. In AID, > 94.2% of the respondents would not support a preventive adaptation of the immunomodulating therapy. In case of mild COVID-19, more than 50% of the respondents would continue pre-existing treatment with immunoglobulins (100%), hydroxychloroquine (94.2%), anakinra (79.2%) or canakinumab (72.5%), or tocilizumab (69.8%). Long-term corticosteroids would be reduced by 26.9% ( 2 mg/kg/day), respectively, with only 5.8% of respondents voting to discontinue the therapy. Conversely, more than 75% of respondents would refrain from administering cyclophosphamide and anti-CD20-antibodies. As evidence on management of pediatric COVID-19 is incomplete, continuous and critical expert opinion and knowledge exchange is helpful. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04824-4.

Recent decades have seen the introduction of many new therapeutics into pediatric rheumatology practice, particularly biologic disease-modifying antirheumatic drugs (bDMARD). These advances are a result of the biotechnological revolution in the pharmaceutical industry, specific legislation for the development of pediatric medicines, and large international collaborative networks. The bDMARD have increased the probability of achieving challenging therapeutic goals such as remission in juvenile idiopathic arthritis (JIA). According to data from recent inception cohort studies in Canada and Germany, 75–81% of newly diagnosed JIA patients reached inactive disease during the first year of treatment, with 21–35% of cases receiving bDMARD1,2. There is growing evidence that rapid and aggressive disease control through early effective treatment is crucial for the further course and outcome of JIA3,4,5. For this reason, an international task force of 30 pediatric rheumatologists has recommended that a clinically inactive disease should be reached within the first 6 months of treatment by means of a treat-to-target approach6. If this therapeutic target, or at least minimal (or low) disease activity, has not been achieved, escalation of therapy (e.g., the use of one bDMARD or switching to another bDMARD) is recommended. However, we are currently not in a position to predict drug outcomes, either at the start of treatment or at a time when treatment needs to be modified or escalated to maximize therapeutic outcomes. Despite the advances in treatment, managing JIA still often follows a trial-and-error principle. Patients with JIA may have to spend a lifetime testing medications that may not be effective in treating their condition7. With the ever-increasing number of medications, family and provider decision making is becoming increasingly complex, including the choice of … Address correspondence to Dr. K. Minden, Charite – Universitatsmedizin Berlin, Department of Rheumatology and Clinical Immunology, German Rheumatism Research Center, Epidemiology Unit, Chariteplatz 1, 10117 Berlin, Germany. Email: minden{at}drfz.de.

ObjectivesThis study aimed to investigate the clinical manifestations, course and outcome of SARS-CoV-2 infection among children and adolescents with rheumatic and musculoskeletal diseases (RMD). Due to their underlying disease as well due to therapeutic immunosuppression, these patients may be at risk for a severe course of COVID-19 or for a flare of the underlying disease triggered by SARS-CoV-2 infection.MethodsDemographic, clinical and treatment data from juvenile patients with RMD as well as data about SARS-CoV-2 infection like test date and method, clinical characteristics, disease course, outcome and impact on the disease activity of the RMD were documented on a specific SARS-CoV-2 questionnaire implemented in the National Paediatric Rheumatology Database (NPRD) in Germany. The survey data were analysed descriptively.ResultsFrom 17 April 2020 to 16 February 2021, data were collected from 76 patients (52% female) with RMD and laboratory-proven SARS-CoV-2 infection with median age of 14 years, diagnosed with juvenile idiopathic arthritis (58%), autoinflammatory (24%) and connective tissue disease (8%). Fifty-eight patients (76%) received disease-modifying antirheumatic drugs (DMARDs), 41% biological DMARDs and 11% systemic glucocorticoids. Fifty-eight (76%) had symptoms of COVID-19. Disease course of SARS-CoV-2 infection (classified as asymptomatic, mild, moderate, severe, life-threatening) was mild and outcome of COVID-19 (classified as recovered, not yet recovered, permanent damage or deceased) was good (recovered) in the majority of patients. Two patients were hospitalised, one of whom required intensive care and died of cardiorespiratory failure. In 84% of SARS-CoV-2-positive patients, no relevant increase in disease activity of the RMD was observed.ConclusionsIn our cohort, SARS-CoV-2 infection in juvenile patients with RMD under various medications was mild with good outcome in the majority of cases and does not appear to have a relevant impact on disease activity of the underlying condition.

Objectives To determine (i) correlates for etanercept (ETA) discontinuation after achieving an inactive disease and for the subsequent risk of flare and (ii) to analyze the effectiveness of ETA in the re-treatment after a disease flare. Methods Data from two ongoing prospective registries, BiKeR and JuMBO, were used for the analysis. Both registries provide individual trajectories of clinical data and outcomes from childhood to adulthood in juvenile idiopathic arthritis (JIA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs (csDMARDs). Results A total of 1724 patients were treated first with ETA treatment course (338 with second, 54 with third ETA course). Similar rates of discontinuation due to ineffectiveness and adverse events could be observed for the first (19.4%/6.2%), second (18.6%/5.9%), and third (14.8%/5.6%) ETA course. A total of 332 patients (+/−methotrexate, 19.3%) discontinued ETA after achieving remission with the first ETA course. Younger age (hazard ratio (HR) 1.08, p p = 0.004), and shorter duration between JIA onset and ETA start (HR 1.10, p p n = 117 of 161; 72.7%) after the flare. One in five patients (n = 23, 19.7%) discontinued ETA again after achieving an inactive disease and about 70% of the patients achieved an inactive disease 12 months after restarting ETA. Conclusion The study confirms the effectiveness of ETA even for re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher rate of inactive disease indicating a window of opportunity.

Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.

Contains fulltext : 231528.pdf (Publisher’s version ) (Closed access) BACKGROUND: TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking. OBJECTIVE: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses. METHODS: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. RESULTS: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P < .02) and higher efficacy rate of on-demand nonsteroidal anti-inflammatory drugs (P 85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies. CONCLUSION: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment.

Background At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR). Methods JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 to March 2019, and baseline characteristics, effectiveness, and safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, and ACR-inactive disease definition. Safety assessments were based on adverse event (AE) reports. Results A total of 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug, and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after nine years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p = 0.3] and 52 SAEs (1.4/100PY; p = 0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p = 0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p = 0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p = 0.015) for inflammatory bowel disease, and 1.9/100PY and 1.4/100PY (p = 0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively. Conclusions No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment.

Objective.Enthesitis-related arthritis (ERA) represents a subgroup of juvenile idiopathic arthritis (JIA) that is regularly accompanied by anterior uveitis. This study describes the prevalence and characteristics of ERA-related uveitis.Methods.Cross-sectional data from the National Pediatric Rheumatological Database (NPRD) were used to characterize ERA-related uveitis (ERA-U). In addition to sociodemographic variables, we documented the occurrence of uveitis and course of disease, including symptoms, visual acuity, and complications, as well as JIA characteristics such as disease activity (Juvenile Arthritis Disease Activity Score 10), functional ability (Childhood Health Assessment Questionnaire score), laboratory variables, and treatment.Results.In the years from 2002 to 2014, there were 3778 (15.2%) of a total of 24,841 JIA patients recorded in the NPRD who had ERA, and 280 (7.4%) of them had developed uveitis. Detailed ophthalmological documentation by a uveitis add-on module was available for 22.9% of these patients. Uveitis onset was acutely symptomatic in 63% of patients. Patients with uveitis were more frequently male, HLA-B27–positive, younger at ERA onset, and they had higher erythrocyte sedimentation rate values at first uveitis documentation than those without uveitis. Uveitis was diagnosed at a mean age of 11.5 (± 3.9) years (50% within 2 years after ERA onset). Systemic treatment with corticosteroids and synthetic and biologic disease-modifying antirheumatic drugs was associated with a (not significantly) lower risk of developing uveitis.Conclusion.The course of disease in ERA-U patients is frequently similar to HLA-B27–associated uveitis in adults; however, a subgroup of patients presents with asymptomatic uveitis.

BackgroundJuvenile idiopathic arthritis is one of the most prevalent chronic inflammatory diseases in children. Evidence suggests that early effective treatment minimises the burden of disease during childhood and in further life. We hypothesise that a guided treat-to-target (T2T) approach is superior to routine care in polyarticular juvenile idiopathic arthritis (pJIA) in terms of reaching a clinical remission after 12 months of treatment.MethodsPatients with early and active pJIA were enrolled. Targets for treatment were the following: Recognisable Juvenile Arthritis Disease Activity Score (JADAS) improvement after 3 months, acceptable disease at 6 months, minimal disease activity at 9 months and as primary endpoint remission after 12 months. Initially, patients received methotrexate. Failure to meet a defined target required treatment modification at the specified intervals. The choice of biologics was not influenced by the protocol. Finally, T2T patients were compared with a cohort of matched controls of patients with pJIA with unguided therapy documented by BIKER.ResultsSixty-three patients were enrolled. Treatment targets after 3/6/9 and 12 months were reached by 73%/75%/77% and 48% of patients. Fifty-four patients completed the protocol. Compared with matched controls, on T2T guidance significantly more patients reached JADAS remission (48% vs 32%; OR 1.96 (1.1–3.7); p=0.033) and JADAS minimal disease activity (JADAS-MDA) (76% vs 59%; OR 2.2 (1.1–4.4); p=0.028). Patients from the T2T cohort received a biologic significantly more frequent (50% vs 9% after 12 months; OR 9.8 (4.6–20.8); pConclusionThe T2T concept was feasible and superior to unguided treatment. High rates of patients reached JADAS-MDA and JADA remission after 12 months. Approximately half of the patients achieved their therapy goals without a biologic.

OBJECTIVE To analyze the prognostic value of demographic, clinical, and therapeutic factors and laboratory biomarkers and to assess their role in predicting uveitis occurrence in patients with juvenile idiopathic arthritis (JIA). METHODS Patients with JIA were enrolled within the first year after JIA diagnosis. Demographic and clinical parameters were documented. Serum samples were collected at study enrollment, at 3-month follow-up visits within the first year, and then every 6 months. A multivariable Cox regression analysis was performed to evaluate the impact of demographic, clinical, laboratory, and therapeutic parameters on uveitis onset. RESULTS We included 954 JIA patients (67.2% female, 54.2% antinuclear antibody [ANA] positive, mean ± SD age at onset 7.1 ± 4.6 years). Uveitis occurred in 133 patients (observation period 44.5 months). Young age at JIA onset and ANA positivity were significantly associated with the onset of uveitis (both P < 0.001). Treatment of arthritis with methotrexate alone (hazard ratio [HR] 0.18 [95% confidence interval (95% CI) 0.12-0.29], P < 0.001) or combined with etanercept (HR 0.10 [95% CI 0.04-0.23], P < 0.001) or adalimumab (HR 0.09 [95% CI 0.01-0.61], P = 0.014) reduced the risk of uveitis onset and the occurrence of uveitis-related complications. Predictors of uveitis onset included elevated erythrocyte sedimentation rate at baseline (HR 2.36 [95% CI 1.38-4.02], P = 0.002) and continuing moderate or high disease activity during follow-up as measured by the 10-joint clinical Juvenile Arthritis Disease Activity Score (HR 4.30 [95% CI 2.51-7.37], P < 0.001). Additionally, S100A12 levels ≥250 ng/ml at baseline were significantly associated with the risk of uveitis (HR 2.10 [95% CI 1.15-3.85], P = 0.016). CONCLUSION Apart from demographic risk factors and treatment modalities, JIA disease activity scores and laboratory biomarkers could be used to better define the group of JIA patients at high risk of uveitis onset.

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

Zusammenfassung Hintergrund Multizentrische Beobachtungsstudien, wie die Kerndokumentation rheumakranker Kinder und Jugendlicher, und bundesweite Abrechnungsdaten vermitteln Informationen zur Versorgung von Kindern, Jugendlichen und jungen Erwachsenen mit juveniler idiopathischer Arthritis (JIA). Sie gestatten die Art der Versorgung, deren Veränderungen über die Zeit und assoziierte Outcomes sowie Defizite aufzuzeigen. Methoden Basierend auf Daten der Kerndokumentation, der Umfrage der kinderrheumatologischen Fachgesellschaft zu Versorgungsangeboten in 2017 und Publikationen der letzten Jahre wird die Versorgungssituation bei der JIA zusammenfassend dargestellt. Zur Beurteilung der Krankheitslast wurden neben der in der Kerndokumentation erfassten Krankheitsaktivität (beurteilt anhand des klinischen JADAS-10 [juvenile arthritis disease activity score]) die patienten-berichteten Outcomes Funktionsfähigkeit (bestimmt mittels Childhood Health Assessment Questionnaire) und Schmerzen (erfasst mittels numerischer Ratingskala) herangezogen. Ergebnisse Für die Behandlung rheumakranker Kinder und Jugendlicher stehen inzwischen bundesweit über 160 Kinder- und Jugendrheumatologen zur Verfügung. Die Versorgung der jungen Patienten erfolgt überwiegend an Krankenhausambulanzen, die Häufigkeit stationärer Behandlungen ist jedoch zurückgegangen. Die medikamentöse Therapie unterlag erheblichen Änderungen, in 2016 wurden 22% aller JIA-Patienten mit Biologika behandelt, von den Patienten mit systemischer JIA sogar fast 40%. Glukokortikoide und NSAR haben mit zunehmendem Biologikaeinsatz an Bedeutung verloren. Die Krankheitslast war bei den Kindern und Jugendlichen mit JIA in den letzten Jahren rückläufig. Sowohl die durchschnittliche Krankheitsaktivität als auch die Funktionseinschränkungen im Alltag sind zurückgegangen, die mittlere Schmerzstärke der Betroffenen änderte sich über die Zeit jedoch nicht relevant. Schätzungsweise mindestens zwei Drittel der JIA-Patienten werden im Kindes- und Jugendalter fachspezifisch versorgt. Im jungen Erwachsenenalter sind es weniger, was Konsequenzen für die medikamentöse Versorgung der Betroffenen hat. Fazit Mit den heute vorhandenen Versorgungsangeboten und Therapiestrategien lässt sich die Krankheitslast bei den JIA-Patienten erfolgreich reduzieren. Damit Patienten von den neuen Optionen profitieren können, braucht es eine rechtzeitige Erkennung der JIA mit Überweisung und langfristigem Verbleiben in fachspezifischer Betreuung.

Background Achieving the best possible health-related quality of life (HRQoL) for a patient is an important treatment goal in juvenile idiopathic arthritis (JIA). We investigated the 36-month trajectories of HRQoL in children with JIA compared with healthy peers and identified the predictors of an unfavorable HRQoL. Methods Patients with a recent JIA diagnosis were enrolled in the German inception cohort study ICON. As a peer group, friends of patients of the same age and sex were asked to cooperate. Children were prospectively followed and regularly questioned about their HRQoL using the Pediatric Quality of Life Inventory 4.0 (PedsQL). Disease activity was assessed by the clinical Juvenile Arthritis Disease Activity Score (cJADAS-10), and the burden of the child’s chronic illness on their family was assessed by the Family Burden Questionnaire (FaBel). Linear mixed models were used to compare the HRQoL of the patients and their peers. Associations between the health status of a patient at enrollment and an unfavorable HRQoL (PedsQL total

Zielsetzung: Aktualisierung der bestehenden deutschsprachigen interdisziplinaren Leitlinie zur Therapie der juvenilen idiopathischen Arthritis (JIA)-assoziierten Uveitis aufgrund der aktuellen Literatur. Material und Methoden: Die Leitliniengruppe bestand aus Delegierten der Deutschen Ophthalmologischen Gesellschaft, der Gesellschaft fur Kinder- und Jugendrheumatologie, der Deutschen Gesellschaft fur Rheumatologie, des Berufsverbandes der Augenarzte Deutschlands und Patientenvertretern. Die Methodik umfasste eine systematische Literaturrecherche, eine Graduierung von Evidenz und Empfehlungen, eine Konsensusfindung mittels nominalem Gruppenprozess und Delphirunden und eine externe Begutachtung. Ergebnisse: Entsprechend dem individuellen Schweregrad der Uveitis kann eine qualitative hochwertige Versorgung der Patienten erzielt werden. Berucksichtigung finden Kortikosteroide, konventionell synthetische (cs) und biologische (b) disease-modifying anti-rheumatic drugs (DMARDs), einschlieslich TNF-α-Inhibitoren (z. B. Adalimumab, Golimumab, Infliximab), Tocilizumab, Abatacept und Rituximab. Schlussfolgerungen: Mit der Leitlinie wird ein aktueller Therapiealgorithmus mit Darstellung als Flussdiagramm erarbeitet. Goal: Revision of the German interdisciplinary guideline on the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis with appreciation of recently published data. Material and methods: The guideline group comprised delegates from German Ophthalmological Society, Society for Child and Adolescent Rheumatology, German Society of Rheumatology, Professional Association of Ophthalmologists, and patient representatives. Methods included systematic literature survey, gradation of evidence and recommendations, consensus process (Delphi procedure), and external review. Results: Adjusted to disease severity in the individual case, a high-quality patient care can be ensured. Corticosteroids, conventional synthetic (cs) and biological (b) disease-modifying anti-rheumatic drugs (DMARDs) are taken into account, including TNFα inhibitors (e. g. adalimumab, golimumab, infliximab), tocilizumab, abatacept and rituximab. Conclusions: Within the guideline, a current treatment algorithm with presentation as flow diagrams is established.

To determine the prevalence of type 1 diabetes mellitus (T1D) in patients with juvenile idiopathic arthritis (JIA) and to characterize patients having both.Diabetes comorbidity was recorded in the National Pediatric Rheumatologic Database since 2012. Data from the North Rhine-Westphalian diabetes registry served as the reference population for the prevalence of diabetes in the general population. The National Pediatric Rheumatologic Database data were indirectly standardized for age and sex for comparison with the general population. The diabetes prevalence ratio was calculated using the Poisson regression model.The analysis included 12 269 patients with JIA. A total of 58 patients had comorbid T1D, and the diabetes prevalence was 0.5%. The mean age was 11.6 years at the time of documentation, and the mean disease duration was 4.2 years. Compared with the general population, the prevalence of diabetes in patients with JIA was significantly increased (prevalence ratio 1.76 [95% CI 1.34; 2.28], P .001). The onset of diabetes in patients with JIA was earlier than that reported in the reference data. Sixty-three percent of patients developed T1D before JIA. On average, diabetes onset was 56 months before the onset of JIA. Patients who first developed JIA developed T1D on average 40 months later. The majority of patients had not received disease-modifying antirheumatic drugs before diabetes onset.T1D occurs more frequently in patients with JIA than in the general population. The likelihood of T1D occurrence appears to be slightly higher before JIA manifestation and without disease-modifying antirheumatic drug therapy after JIA onset.

Background:Juvenile idiopathic arthritis (JIA) associated uveitis is an extra-articular manifestation of the JIA disease that may cause vision-threatening complications and an uncontrolled uveitis may even lead to blindness. Uveitis occurs in up to 20% of patients with JIA, depending on the JIA category. The majority of patients develop uveitis within the first two years after JIA symptom onset, but uveitis can continue into adulthood.Objectives:The main objective of this study was to analyze the risk for uveitis events after discontinuing disease-modifying antirheumatic drugs (DMARD) in patients with extended oligoarthritis and rheumatoid factor (RF)-negative polyarthritis.Methods:Data of the two ongoing multicenter biologic registers: German Biologics in Pediatric Rheumatology (BiKeR) and the Juvenile arthritis Methotrexate/Biologics long-term Observation (JuMBO) were used to analyze the adverse-event (AE) and events of special interest (ESI) reports about uveitis events during treatment and after discontinuation of DMARDs. Biker started recruitment of children and adolescent patients with JIA exposed to biological (b) or conventional (cs) DMARD’s in 2001. The patients were further followed in JuMBO after reaching the age of 18 or transitioning to an adult rheumatologist. Disease characteristics, treatment data, AE’s and ESI’s were reported by the pediatric or adults rheumatologist, respectively.Results:A total of 2,041 patients with RF-negative polyarthritis (n=1,280) or extended oligoarthritis (n=761) were included into the analyses. The mean follow-up of this study was 7.6 years (SD 5.3). About half of the patients were enrolled in BiKeR with start of etanercept (1,137, 55.7%), followed by 635 (31.1%) patients with start of methotrexate (MTX) monotherapy or adalimumab (ADA, n=198, 9.7%). A history of uveitis was reported for 238 (11.7%) patients at enrolment in BiKeR. More patients with a history of uveitis treated with ADA were included in BiKeR initiating ADA (n=98 of 238, 41.2%). Patients with uveitis had a lower age at JIA onset in comparison to patients without uveitis (mean 3.6 (SD 3.0) versus 7.0 (SD 4.5) years). A total of 142 recurrent (84% of 169) uveitis events were reported in 93 patients and for 27 patients (1.3% of 2,041) was an incident uveitis reported during follow-up. More than one uveitis event was reported for 32 patients with a maximum number of 4 uveitis flares in 3 patients. Nineteen uveitis flares (11.2% of 169) were reported for patients after the age of 18. The longer the time since DMARD discontinuation the fewer uveitis events occurred. Uveitis events were significantly more often reported in the first 24 months after MTX discontinuation (2 at last MTX intake had a higher likelihood for uveitis events (OR=1.40, 95%CI: 1.02 to 1.92).Conclusion:This is the first study that analyzed the risk of uveitis after DMARD withdrawal. Uveitis relapses are common. Patients who discontinued DMARD therapy were at high risk for uveitis within the first 3 to 24 months after discontinuation. Rheumatologists and ophthalmologists should be aware about this risk which should lead to a regular uveitis screening after DMARD withdrawal.Disclosure of Interests:Jens Klotsche: None declared, Ariane Klein: None declared, Martina Niewerth: None declared, Tilmann Kallinich: None declared, Daniel Windschall: None declared, Johannes-Peter Haas: None declared, Frank Weller-Heinemann Speakers bureau: Pfizer, Abbvie, SOBI, Roche, Novartis, Toni Hospach: None declared, Frank Dressler: None declared, Kirsten Minden: None declared, Gerd Horneff: None declared

Key Points Question Does pediatrician training in motivational interviewing (MI) facilitate the use of mental health care services for youths with chronic medical conditions? Findings In this cluster randomized trial with 164 youths with chronic medical conditions and comorbid anxiety or depression, training physicians in MI did not significantly improve uptake rates of psychological counseling among youths compared with usual care. MI training was associated with longer patient-physician conversations and lower anxiety scores at 1-year rescreening. Meaning More research is needed to determine whether training pediatricians in MI and allotting more consultation time to discuss mental health could facilitate use of counseling services by youths with chronic medical conditions., This cluster randomized clinical trial examined the efficacy of pediatricians using motivational interviewing (MI) vs treatment as usual in increasing youths’ utilization of mental health care., Importance Despite the high prevalence of anxiety and depression in youths with chronic medical conditions (CMCs), physicians encounter substantial barriers in motivating these patients to access mental health care services. Objective To determine the efficacy of motivational interviewing (MI) training for pediatricians in increasing youths’ use of mental health care. Design, Setting, and Participants The COACH-MI (Chronic Conditions in Adolescents: Implementation and Evaluation of Patient-Centered Collaborative Healthcare—Motivational Interviewing) study was a single-center cluster randomized clinical trial at the University Children’s Hospital specialized outpatient clinics in Düsseldorf, Germany. Treating pediatricians were cluster randomized to a 2-day MI workshop or treatment as usual (TAU). Patient recruitment and MI conversations occurred between April 2018 and May 2020 with 6-month follow-up and 1-year rescreening. Participants were youths aged 12 to 20 years with CMCs and comorbid symptoms of anxiety and depression; they were advised by their MI-trained or untrained physicians to access psychological counseling services. Statistical analysis was performed from October 2020 to April 2021. Interventions MI physicians were trained through a 2-day, certified MI training course; they recommended use of mental health care services during routine clinical appointments. Main Outcomes and Measures The primary outcome of uptake of mental health care services within the 6-month follow-up was analyzed using a logistic mixed model, adjusted for the data’s cluster structure. Uptake of mental health services was defined as making at least 1 appointment by the 6-month follow-up. Results Among 164 youths with CMCs and conspicuous anxiety or depression screening, 97 (59%) were female, 94 (57%) had MI, and 70 (43%) had TAU; the mean (SD) age was 15.2 (1.9) years. Compared with patients receiving TAU, the difference in mental health care use at 6 months among patients whose physicians had undergone MI training was not statistically significant (odds ratio [OR], 1.96; 95% CI, 0.98-3.92; P = .06). The effect was moderated by the subjective burden of disease (F2,158 = 3.42; P = .04). Counseling with an MI-trained physician also led to lower anxiety symptom scores at 1-year rescreening (F1,130 = 4.11; P = .045). MI training was associated with longer conversations between patients and physicians (30.3 [16.7] minutes vs 16.8 [12.5] minutes; P

For young people with rheumatic diseases, the transition from paediatric to adult rheumatology care is a vulnerable time, and delays or disruption in their care can lead to adverse outcomes. Research into the factors associated with gaps in transitional care could improve the identification and targeting of vulnerable groups.

Annals of the rheumatic diseases 76(5), 906-913 (2017). doi:10.1136/annrheumdis-2016-210324, Published by BMJ Publ. Group, London

Background JIA-associated uveitis (JIAU) is a serious, sight-threatening disease with significant long-term complications and risk of blindness, even with improved contemporary treatments. The MIWGUC was set up in order to propose specific JIAU activity and response items and to validate their applicability for clinical outcome studies. Methods The group consists of 8 paediatric rheumatologists and 7 ophthalmologists. A consensus meeting took place on November 2015 in Barcelona (Spain) with the objective of validating the previously proposed measures. The validation process was based on the results of a prospective open, international, multi-centre, cohort study designed to validate the outcome measures proposed by the initial MIWGUC group meeting in 2012. The meeting used the same Delphi and nominal group technique as previously described in the first paper from the MIWGUC group (Arthritis Care Res 64:1365–72, 2012). Patients were included with a diagnosis of JIA, aged less than 18 years, and with active uveitis or an uveitis flare which required treatment with a disease-modifying anti-rheumatic drug. The proposed outcome measures for uveitis were collected by an ophthalmologist and for arthritis by a paediatric rheumatologist. Patient reported outcome measures were also measured. Results A total of 82 patients were enrolled into the validation cohort. Fifty four percent (n = 44) had persistent oligoarthritis followed by rheumatoid factor negative polyarthritis (n = 15, 18%). The mean uveitis disease duration was 3.3 years (SD 3.0). Bilateral eye involvement was reported in 65 (79.3%) patients. The main findings are that the most significant changes, from baseline to 6 months, are found in the AC activity measures of cells and flare. These measures correlate with the presence of pre-existing structural complications and this has implications for the reporting of trials using a single measure as a primary outcome. We also found that visual analogue scales of disease activity showed significant change when reported by the ophthalmologist, rheumatologist and families. The measures formed three relatively distinct groups. The first group of measures comprised uveitis activity, ocular damage and the ophthalmologists’ VAS. The second comprised patient reported outcomes including disruption to school attendance. The third group consisted of the rheumatologists’ VAS and the joint score. Conclusions We propose distinctive and clinically significant measures of disease activity, severity and damage for JIAU. This effort is the initial step for developing a comprehensive outcome measures for JIAU, which incorporates the perspectives of rheumatologists, ophthalmologists, patients and families.

Background Although juvenile idiopathic arthritis (JIA) occurs early in life, patients can require long-term treatment into adulthood due to active disease or flares. However, most available studies show that there are gaps in care during and after the transition to adult care. Transition has been associated with higher dropout rates, and there is limited evidence on treatment persistence in JIA patients. The current analysis evaluates etanercept bio-original (ETNBo) persistence up to 5 years and reports diagnostic patterns in early adolescence and young adults in Germany. Methods Patients with JIA (ICD10: M08) between 2-30 years of age with a first recorded ETNBo prescription between 1-January-2008 and 31-December-2012 were retrospectively identified in German health insurance claims data. Patients were followed until 31-December-2015 or end-of-record, whichever came first. Index date was set at the first ETNBo prescription after a 12-month etanercept-free look-back period. Patient characteristics, concomitant treatments and prior use of other biologic Disease-modifying antirheumatic Drugs (bDMARD) were evaluated in the 12-month look-back period. The 5-year etanercept treatment persistence, defined as median (95% confidence interval [CI]) months between the index date and a discontinuation (≥90-day treatment gap after last etanercept prescription), was estimated using Kaplan-Meier analysis, overall and for bio-naïve patients. Etanercept WHO defined daily dose (DDD) was adjusted by age; for patients 2-6, 7-10, 11-14 and >15 daily doses were defined as 1.4mg, 3.6mg, 5.4mg and 7.0mg, respectively. The proportion of patients receiving an adult rheumatic diagnosis after the age of 11 was described. Results We identified 125 patients diagnosed with JIA (median age: 15 years; 30% male). At index quarter 56% of patients were in the 11-20 age group. Most patients (94%) were bio-naïve and 46%, 34%, and 17% had concomitant use of NSAIDS, other DMARDS, and corticosteroids, respectively. Overall median persistence was 13 months (95%CI: 10-16; IQR: 5-27). Persistence for the bio-naïve patients was 50% (95%CI: 41-57), 27% (95%CI: 20-34), 16% (95%CI: 10-23), 10% (95%CI: 5-17) and 9% (95%CI: 4-15) at 12, 24, 36, 48, and 60 months respectively. The majority of patients (68%) received an additional diagnosis of rheumatoid arthritis after age 11, while 15% were given other adult rheumatic diagnoses. Only 9% of JIA patients had received no additional diagnosis to JIA. Conclusion This analysis provides important understanding of care in young JIA patients. We observed a decreasing persistence of etanercept therapy as patients progressed in time through the transition period into early adulthood. Importantly, we found that the majority of JIA patients received additional adult diagnoses, which suggests the transition could impact on the clinical management of this disease. Diagnostic patterns, clinical and patient circumstances during this critical period and their impact on persistence requires further analysis. Conflicts of Interest The authors declare no conflicts of interest.

Background Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in a 1 000 000 children(1). Currently there is nearly no data published about the course of jSSc patients with standardized assessment. We report our date from Juvenile Scleroderma Inception cohort (JSSIC) with a follow up of 24 months. Objectives: to evaluate the organ involvement and patient reported outcomes (PRO) during the first 24 months in the JSIC Methods The JSSIC is a prospective multicenter registry of patients with jSSc, who fulfill the adult classification criteria(2), and presented the first non-Raynaud symptom before 16 years of age and were younger then 18 years at the time of inclusion in the JSSIC. Patients who were followed at least 24 months in the JSSIC, were evaluated. Results 52 patients were followed at least 24 months in the registry. 77% were female and 77% had diffuse subtype. 19% had overlap features. Mean disease duration at time of inclusion was 3.2 years. Mean age of at Raynaud’s onset was 8.8 years and the first non-Raynaud’s symptom 9.4 years. 85% received DMARDs at the time of inclusion and 96% after 24 months. 88% of the patients were ANA positive, 35% anti-Scl70 positive and 3% anticentromere positive. The mean modified skin score decreased from 14.3 to 12.6. The frequency of Raynaud’s stayed around 87%. The frequency of the nailfold capillary changes increased from 56% to 63%, but the frequency of active ulcerations stayed stable around 21%. The number of patients with FVC Several PROs improved significantly. Patient global disease activity (VAS 0-100) changed from 46 to 29 (p=0.002), patient global disease damage (VAS 0-100) from 46 to 28 (p=0.02) and patient Raynaud activity VAS 0-100) from 27 to 14 (p=0.009) as physician global disease activity (VAS 0-100) from 43 to 29 (p=0.021) and physician global disease damage from 46 to 28 (P=0.01). Conclusion Over the 24 months observation period patient and physician related outcomes improved significantly. Regarding organ involvement there was an increase in patients of pulmonary hypertension and joint contractures. References [1] Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States. Journal of Scleroderma and Related Disorders. 2018;3(2):189-90. [2] van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737-47. Disclosure of Interests Ivan Foeldvari Consultant for: Chugai, Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Maria T. Tererri: None declared, Jordi Anton Grant/research support from: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Consultant for: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Speakers bureau: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Tadej Avcin: None declared, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Maria Katsikas: None declared, Dana Nemcova: None declared, Maria Jose Santos: None declared, Cristina Battagliotti: None declared, Lillemor Berntson: None declared, Juergen Brunner: None declared, Liora Harel: None declared, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Kirsten Minden Consultant for: AbbVie, Monika Moll: None declared, Anjali Patwardhan: None declared, Kathryn Torok: None declared, Nicola Helmus: None declared