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Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole.Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay.Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups.Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

International audience; Eosinophils play a homeostatic role in the body's immune responses. These cells are involved in combating some parasitic, bacterial, and viral infections and certain cancers and have pathologic roles in diseases including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal disorders, and hypereosinophilic syndromes. Treatment of eosinophilic diseases has traditionally been through nonspecific eosinophil attenuation by use of glucocorticoids. However, several novel biologic therapies targeting eosinophil maturation factors, such as interleukin (IL)-5 and the IL-5 receptor or IL-4/IL-13, have recently been approved for clinical use. Despite the success of biologic therapies, some patients with eosinophilic inflammatory disease may not achieve adequate symptom control, underlining the need to further investigate the contribution of patient characteristics, such as comorbidities and other processes, in driving ongoing disease activity. New research has shown that eosinophils are also involved in several homeostatic processes, including metabolism, tissue remodeling and development, neuronal regulation, epithelial and microbiome regulation, and immunoregulation, indicating that these cells may play a crucial role in metabolic regulation and organ function in healthy humans. Consequently, further investigation is needed into the homeostatic roles of eosinophils and eosinophil-mediated processes across different tissues and their varied microenvironments. Such work may provide important insights into the role of eosinophils not only under disease conditions but also in health. This narrative review synthesizes relevant publications retrieved from PubMed informed by author expertise to provide new insights into the diverse roles of eosinophils in health and disease, with particular emphasis on the implications for current and future development of eosinophil-targeted therapies.

Uncontrolled airway mucus is associated with diverse diseases. We hypothesized that the physical characteristics of infiltrating granulocytes themselves affect the clinical properties of mucus. Surgically obtained nasal mucus from patients with eosinophilic chronic rhinosinusitis (ECRS) and neutrophil-dominant non-eosinophilic chronic rhinosinusitis (non-ECRS) was assessed in terms of computed tomography (CT) density, viscosity, water content, wettability, and granulocyte-specific proteins. In an observational study, we found that nasal mucus from patients with ECRS had significantly higher CT density, viscosity, dry weight, and hydrophobicity than mucus from patients with non-ECRS. The levels of eosinophil-specific proteins in nasal mucus correlated with its physical properties. When isolated human eosinophils and neutrophils were stimulated to induce extracellular traps followed by aggregate formation, we found that cell aggregates showed physical and pathological findings that closely resembled mucus. Co-treatment with heparin (which slenderizes the structure of eosinophil extracellular traps) and DNase efficiently induced a reduction in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. The present study highlights the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a new perspective. The combination of DNase and heparin might be a novel therapeutic modality against pathologic viscous eosinophilic mucus.One Sentence SummaryIntraluminal accumulation and activation of eosinophils contribute to the clinical properties of airway mucus and may serve as a therapeutic target.

Eosinophilic diseases, also termed eosinophil-associated diseases (EADs), are characterized by eosinophil-rich inflammatory infiltrates and extensive eosinophil degranulation with clinically relevant organ pathology. Recent evidence shows that eosinophil cytolytic degranulation, that is, the release of intact, membrane-delimited granules that arises from the eosinophil cytolysis, occurs mainly through ETosis, meaning death with a cytolytic profile and extrusion of nucleus-originated DNA extracellular traps (ETs). The ultrastructural features of eosinophil ETosis (EETosis) have been studied mostly in vitro after stimulation, but are still poorly understood in vivo. Here, we investigated in detail, by transmission electron microscopy (TEM), the ultrastructure of EETosis in selected human EADs affecting several tissues and organ systems. Biopsies of patients diagnosed with eosinophilic chronic rhinosinusitis/ECRS (frontal sinus), ulcerative colitis/UC (intestine), and hypereosinophilic syndrome/HES (skin) were processed for conventional TEM. First, we found that a large proportion of tissue-infiltrated eosinophils in all diseases (~45-65% of all eosinophils) were undergoing cytolysis with release of free extracellular granules (FEGs). Second, we compared the morphology of tissue inflammatory eosinophils with that shown by in vitro ETosis-stimulated eosinophils. By applying single-cell imaging analysis, we sought typical early and late EETosis events: chromatin decondensation; nuclear delobulation and rounding; expanded nuclear area; nuclear envelope alterations and disruption; and extracellular decondensed chromatin spread as ETs. We detected that 53% (ECRS), 37% (UC), and 82% (HES) of all tissue cytolytic eosinophils had ultrastructural features of ETosis in different degrees. Eosinophils in early ETosis significantly increased their nuclear area compared to non-cytolytic eosinophils due to excessive chromatin decondensation and expansion observed before nuclear envelope disruption. ETosis led not only to the deposition of intact granules, but also to the release of eosinophil sombrero vesicles (EoSVs) and Charcot-Leyden crystals (CLCs). Free intact EoSVs and CLCs were associated with FEGs and extracellular DNA nets. Interestingly, not all cytolytic eosinophils in the same microenvironment exhibited ultrastructure of ETosis, thus indicating that different populations of eosinophils might be selectively activated into this pathway. Altogether, our findings captured an ultrastructural signature of EETosis in vivo in prototypic EADs highlighting the importance of this event as a form of eosinophil degranulation and release of inflammatory markers (EoSVs and CLCs).

Eosinophils are short-lived and comprise only a small population of circulating leukocytes; however, they play surprisingly multifunctional roles in homeostasis and various diseases including allergy and infection. Recent research has shed light on active cytolytic eosinophil cell death that releases eosinophil extracellular traps (EETs) and total cellular contents, namely eosinophil extracellular trap cell death (EETosis). The pathological contribution of EETosis was made more cogent by recent findings that a classical pathological finding of eosinophilic inflammation, that of Charcot-Leyden crystals, is closely associated with EETosis. Currently no gold standard methods to identify EETosis exist, but “an active eosinophil lysis that releases cell-free granules and net-like chromatin structure” appears to be a common feature of EETosis. In this review, we describe several approaches that visualize EETs/EETosis in clinical samples and in vitro studies using isolated human eosinophils. EETs/EETosis can be observed using simple chemical or fluorescence staining, immunostaining, and electron microscopy, although it is noteworthy that visualization of EETs is greatly changed by sample preparation including the extracellular space of EETotic cells and shear flow. Considering the multiple aspects of biological significance, further study into EETs/EETosis is warranted to give a detailed understanding of the roles played in homeostasis and disease pathogenesis.

The Charcot–Leyden crystal protein (CLC-P), a constituent of human and not mouse eosinophils, is one of the most abundant proteins within human eosinophils. It has a propensity to form crystalline structures, Charcot–Leyden crystals, which are hallmarks in their distinctive extracellular crystalline forms as markers of eosinophilic inflammation. The functions of CLC-P within eosinophils have been uncertain. Although the action of CLC-P as a lysophospholipase has been questioned, assays of chromatographically purified CLC-P and crystal-derived CLC-P as well as studies of transfected recombinant CLC-P have consistently documented that CLC-P endogenously expresses lysophospholipase activity, releasing free palmitate from substrate lysopalmitoylphosphatidylcholine. Rather than acting solely as a hydrolytic enzyme to release palmitate from a lysolipid substrate, some other lysophospholipases function more dominantly as acyl-protein thioesterases (APTs), enzymes that catalyze the removal of thioester-linked, long chain fatty acids, such as palmitate, from cysteine residues of proteins. As such APTs participate in palmitoylation, a post-translational modification that can affect membrane localization, vesicular transport, and secretion. CLC-P has attributes of an APT. Thus, whereas CLC-P expresses inherent lysophospholipase activity, like some other lysophospholipase enzymes, it likely also functions in regulating the dynamic palmitoylation cycle, including, given its dominant subplasmalemmal location, at the human eosinophil’s plasma membrane.

A predominant protein of human eosinophils is galectin-10 (Gal-10), also known as Charcot-Leyden crystal protein (CLC-P) because of its remarkable ability to form Charcot-Leyden crystals (CLCs), which are frequently found in tissues from patients with eosinophilic disorders. CLC-P/Gal-10 is highly expressed in human eosinophils and considered a biomarker of eosinophil involvement in inflammation. However, the intracellular sites where large pools of CLC-P/Gal-10 constitutively reside are still unclear, and whether this protein is derived or not from eosinophil granules remains to be established. Here, we applied pre-embedding immunonanogold transmission electron microscopy combined with strategies for optimal antigen and cell preservation and quantitative imaging analysis to investigate, for the first time, the intracellular localization of CLC-P/Gal-10 at high resolution in resting and activated human eosinophils. We demonstrated that CLC-P/Gal-10 is mostly stored in the peripheral cytoplasm of human eosinophils, being accumulated within an area of ∼250 nm wide underneath the plasma membrane and not within specific (secretory) granules, a pattern also observed by immunofluorescence. High-resolution analysis of single cells revealed that CLC-P/Gal-10 interacts with the plasma membrane with immunoreactive microdomains of high CLC-P/Gal-10 density being found in ∼60% of the membrane area. Eosinophil stimulation with CCL11 or TNF-α, which are known inducers of eosinophil secretion, did not change the peripheral localization of CLC-P/Gal-10 as observed by both immunofluorescence and immuno-EM (electron microscopy). Thus, in contrast to other preformed eosinophil proteins, CLC-P/Gal-10 neither is stored within secretory granules nor exported through classical degranulation mechanisms (piecemeal degranulation and compound exocytosis).

ZUSAMMENFASSUNGIn unserem Fall wurde die venöse Malformation trotz ihrer Seltenheit rasch festgestellt. Wegweisend für die Diagnose waren die suprapatellare Lokalisation der Schwellung mit medialer Betonung, fehlende Entzündungsparameter im Blut, sowie die Sonografie. Mit dem Kontrastmittel-MRT konnte der Verdacht einer vaskulären Malformation bestätigt und auf eine juxtaartikuläre venöse Malformation präzisiert werden.

BackgroundPsychiatric comorbidities can be a significant additional burden in chronic diseases. The most common chronic inflammatory rheumatic disease in children and adolescents is juvenile idiopathic arthritis (JIA). Data on mental illness in children and adolescents with JIA are heterogeneous.ObjectivesTo assess the frequency of depressive and anxious symptoms in patients with JIA compared to healthy peers.MethodsData were analysed from JIA patients and healthy controls of the same age included in the inception cohort of newly diagnosed children and adolescents with JIA (ICON). Depressive symptoms (using the Patient Health Questionnaire (PHQ-9, score 0-27) and anxious symptoms (Generalised Anxiety Disorder Scale (GAD-7, score 0-21) were captured 7 or 9 years after inclusion in ICON in patients aged thirteen years or older at the time of filling in these questionnaires. Symptom severity for both instruments was assessed by sum score with the following cut-off values: PHQ-9 score < 5: none, 5-9: mild, 10-14: moderate, 15-19: severe, ≥ 20: very severe. GAD-7 Score < 5: none, 5-9: mild, 10-14: moderate, ≥ 15: severe. Disease parameters such as Physician Global Assessment of Disease Activity (PhGA Disease Activity, numerical rating scale, (NRS),0-10, 0=best), joint count (n) and patient-reported outcomes on functional limitations ((C)HAQ, score 0-3, 0=best), Patient Global Assessment of Well-being (PGA Well-being), pain and fatigue (NRS, 0-10, 0=best) were also documented.ResultsThe analysis included 344 patients, 157 (45.6%) < 18 years old (mean 15.5 ± 1.5 years, 64.3% female), 187 (54.4%) ≥ 18 years old (mean 21.5 ± 2.1 years, 65.2% female) and 224 control subjects, 115 (51.3%) < 18 years old (mean 15.2 ± 1.5 years, 60% female), 109 (48.7%) ≥ 18 years old (mean 21.4 ± 1.9 years, 58.7% female). Almost 40% of patients had oligoarthritis (26% persistent OA, 12.5% extended OA), 27% rheumatoid factor (RF)-negative polyarthritis, 6% psoriatic arthritis, 17% enthesitis-related arthritis; 3% each had systemic JIA and RF-positive polyarthritis. In the total cohort, 14% of patients and 7% of controls had a PHQ-9 ≥ 10 and 10% of patients and 2% of controls had a GAD-7 ≥ 10. Within the categories of JIA, the rate of a PHQ-9 ≥ 10 ranged from 9.3% (oligoarthritis extended) to 33.3% (RF-positive polyarthritis) and a GAD-7 ≥ 10 ranged from 0% (systemic arthritis) to 22.2% (psoriatic arthritis).Patients aged ≥ 18 years had higher scores for both PHQ-9 (≥ 10: 18.7%) and GAD-7 (≥ 10: 14.4%) compared to patients < 18 years (PHQ-9 ≥ 10: 8.3%, GAD-7 ≥ 10: 5.1).In patients < 18 years with PHQ-9 < 10 versus ≥ 10, there were no significant differences in either PhGA disease activity (0.8±1.6 / 1.0±2.0, p = 0.673) or joint count (0.5±1.3 / 0.5±1.6, p = 0.999). In contrast, there was a significant difference in PhGA disease activity (0.8±1.5 / 1.6±1.4, p = 0.005) but not in joint count (0.7±3.1 / 0.8±1.3, p = 0.850) in patients ≥ 18 years with PHQ-9 < 10 versus PHQ-9 ≥ 10.Female patients were more often found to have higher scores for depression and anxiety than male patients (PHQ-9 ≥ 10: female 17.5%, male 7.4%, GAD-7 ≥ 10: female 13.5%, male 4.1%) and patients more often had higher scores for depression than controls (PHQ-9 ≥ 10: female patients 17.5%, female controls 8.3%, male patients 7.4%, male controls 4.4%). The difference in the proportion of female patients with GAD-7 ≥ 10 (13.5%) compared to control subjects (2.3%) was remarkable, but in male patients this proportion (4.1%) was only slightly higher than in male control subjects (2.2%).ConclusionDepressive and anxious symptoms are common in adolescents and young adults with JIA, especially in females. In the continuous care of these patients, standardised diagnostic tools should be implemented to detect these comorbidities, to optimise therapy and thereby reduce the burden of disease. Further research is needed to identify possible predictors of the development of depression and anxiety in JIA patients in order to pursue preventive approaches.Disclosure of InterestsPrasad Oommen: None declared, Jens Klotsche: None declared, Frank Dressler: None declared, Ivan Foeldvari: None declared, Dirk Foell: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Abbvie, Grant/research support from: Pfizer, Novartis, MSD, Chugai, Roche, Abbvie, Toni Hospach Consultant of: SOBI, Novartis, Tilmann Kallinich: None declared, Jasmin Kuemmerle-Deschner: None declared, Ina Liedmann: None declared, Kirsten Moenkemoeller: None declared, Martina Niewerth: None declared, Caroline Siemer: None declared, Frank Weller-Heinemann: None declared, Daniel Windschall: None declared, Kirsten Minden Speakers bureau: AbbVie, Pfizer, Novartis, Claudia Sengler: None declared

BackgroundAutoinflammatory diseases (AID) are characterized by severe systemic and organ inflammation as well as high burden of disease for patients and their families. Treatment with the monoclonal antibody canakinumab (CAN), an interleukin-1β inhibitor, has been proven to be safe and effective in clinical trials and real-life.ObjectivesThe present study explores the long-term efficacy and safety of CAN in routine clinical practice conditions in pediatric (age ≥2 years) and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency).MethodsRELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confirmed diagnoses of AID routinely receiving CAN are enrolled. Besides efficacy parameters regarding disease activity and remission, safety parameters were recorded at baseline and assessed at 6-monthly intervals.ResultsHere, we present the interim analysis of patients with AID (N=199) enrolled in the RELIANCE Registry between October 2017 and December 2021. Mean age in this cohort was 24.4 years (2–79 years) and the proportion of female patients was 53% (N=104). At baseline, median duration of prior CAN treatment was 2 years (0–12 years).A total of 123 patients (62%) experienced any AE (N=653) among which nasopharyngitis, increase of inflammatory markers and pyrexia were the most frequent AE with incidence rates per 100 patient years (IR) of 8.3, 6.2, and 6.2, respectively.29 patients (15%) were affected by severe AE (SAE, total number N=90) including 11 patients (6%) with SAE suspected to be drug-related (SADR; total number N=30) with IR from 0.2 to 0.7 (Table 1). Overall, 16 AE comprised upper respiratory tract infections (URI). One death (COVID-19, not related) and one malignancy (skin papilloma, not related) were reported. No vertigo and no hypersensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE).Table 1.Overview of the CAN safety data of the RELIANCE study across all study indications (N=199 patients).Type of eventNumber of eventsIR‡AE total653154.43AE non-serious563133.15AE, non-serious, not related31774.97AE, URI163.78AE, non-serious adverse drug reaction24658.18SAE, total9021.28SAE, not related6014.19SADR#, total307.09#Abdominal pain; Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, Haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tachycardia, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (each n=1 event, IR 0.24‡), tonsillectomy (2 events, IR 0.47‡), pyrexia (3 events, IR 0.71‡), not yet coded (hospital admission due to exsiccosis upon gastroenteritis, 1 event, IR 0.35‡)‡IR, incidence rate per 100 patient years; AE, adverse event; URI, upper respiratory tract infection; SAE, severe adverse event, SADR, severe adverse drug reactionIncidence rate = number of events * 36,525 / sum of observation days (=154,442)ConclusionThe interim data from the RELIANCE study, the longest running real-life canakinumab registry, confirm safety of long-term canakinumab treatment across the entire study population. A trend for dose-related increase of SAE/SADR requires continuous close monitoring and awareness in patient groups (children, severe phenotypes, certain genotypes) requiring greater than standard dose treatment regimens.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Birgit Kortus-Goetze Consultant of: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ales Janda: None declared, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Catharina Schuetz: None declared, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Markus Hufnagel Consultant of: Novartis and SOBI, Florian Meier Speakers bureau: Novartis, Michael Fiene: None declared, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

BackgroundTocilizumab (TCZ) has been approved for treatment of juvenile idiopathic arthritis (JIA) for 10 years.ObjectivesEvaluation of 12-month efficacy and safety of TCZ compared to TNF inhibitors (TNFi).MethodsBIKER WA 29358 is a 5-year multi-centre prospective, observational cohort study including polyarticular JIA patients in Germany starting treatment between 2015 and 2020 with TCZ and matched 1:1 by date of treatment start and region to patients starting an approved TNFi. Clinical disease activity (JADAS10), JADAS MDA (≦3.8)/remission (≦1.0), safety and drug adherence at 12 months were assessed and compared between cohorts.ResultsThe analysis included 342 participants with 12-month treatment data (TCZ n=171; TNFi n=171). TCZ was used as 2nd line biologic in the majority of patients (84%) while TNFi were mostly 1st line biologics (86%). Patients starting TCZ had a longer disease duration. Efficacy was demonstrated by a marked decrease in JADAS10 in both cohorts (TCZ vs. TNFi at baseline: 15.0+/-6.7 vs. 14.6+/-6.3; at month 12: 3.8+/-5.1 vs. 3.4+/-4.5). Proportions of patients in TCZ/TNFi cohorts achieving JADAS remission at 12 months were 48%/41% in 1st line biologic users and 32%/33% in 2nd line biologic users. JADAS MDA was achieved in 64%/69% in 1st line and 52%/58% in 2nd line users of TCZ/TNFi.After 12 months of treatment JADAS10 (mean +/SD) was higher in the 2nd line TNFi cohort compared to the 1st line (4.5+/-5.6 vs. 3.2+/-4.3), similar to patients receiving 2nd or 1st line TCZ (4.0+/-5.2 vs. 2.9+/-4.4). Patients receiving TCZ or TNFi as first biologic reached JADAS10 remission and MDA numerically more frequently but not statistically significant compared to 2nd line users.Safety was assessed based on adverse event (AE) reporting. 57 (33%) patients in the TCZ cohort and 43 (25%) patients in the TNFi cohort reported AE. The AE rate was significantly higher in the TCZ cohort (69 vs. 44.8/100 patient years, RR 1.5 [95%CI 1.1-2.0], p=0.006, Wald-test). There were 6 serious AE in the TCZ and 3 in the TNFi cohort. Injection site reactions were more common in the TNFi cohort (9 vs. 1, p=0.043). No further differences were identified to date. There was no death and no opportunistic infection.In the TCZ cohort, 32 patients discontinued treatment, 27 due to lack of efficacy, while in the TNFi cohort only 6 patients discontinued treatment. Treatment discontinuation was more frequent among the 2nd biologic users (n=29; 17.4%) than in first line users (n= 9; 5.1%).ConclusionIn this first interim analysis, treatment targets were reached with similar frequency after 12 months of treatment with TCZ or TNFi. TCZ was used predominantly as 2nd line biologic. Higher rates of remission /MDA were observed in 1st line compared to 2nd line biologic users. Although more AE were reported in the TCZ cohort, the occurrence of serious AE and infections was comparable in both cohorts. No new safety signals were identified. Observation is ongoing.Table 1.Baseline characteristics and discontinuations with reasons.Number, nTNFi 1st 147TNFi 2nd 24TNFi total 171TCZ 1st 27TCZ 2nd 144TCZ total 171Female, %119(81%)20 (83%)139(81%)20(74%)123(85%)143(84%)Disease duration, years2.7+/-2.76.5+/-3.33.2+/-3.12.5+/-2.75.9+/-4.15.4+/-4.1Pre-treatmentn.a.None=147 (86%)n.a.None=27 (16%)1 biologic14 (58%)14 (8%)80 (56%)80 (47%)2 biologics7 (29%)7 (4%)54 (38%)54 (32%)≥ 3 biologics3 (13%)3 (2%)10 (7%)10 (6%)CHAQ-DI, mean +/- SD0.67+/-0.640.31+/-0.450.63+/-0,630.43+/-0.440.65+/-0.650.61+/-0.62JADAS 10, mean +/- SD14.8+/-6.313.4+/-6.814.6+/-6.313.3+/-6.015.3+/-7.015.0+/-6.7ConcomitantMTX, n (%)120 (82%)13 (54%)133 (78%)17 (63%)75 (52%)92 (54%)Steroid, n (%)37 (25%)4 (17%)41 (24%)8 (30%)35 (24%)43 (25%)Discontinuations, n (%)5 (3.4%)1 (4.2%)6 (3.5%)4 (16%)28 (19%)32 (19%)-Inefficacy1 (0.7%)2 (1.2%)3 (12%)24 (17%)27 (16%)-Intolerance2 (1.4%)1 (4.2%)2 (1.2%)2 (1.4%)2 (1.2%)-Other2 (1.4%)2 (1.2%)1 (4%)4 (2.8%)5 (3.0%)Disclosure of InterestsAriane Klein Speakers bureau: Novartis fee chairing a lunch symposium, Angela Zimmer: None declared, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Sandra Hansmann: None declared, Jasmin Kuemmerle-Deschner: None declared, Maria Fasshauer: None declared, Kirsten Minden Speakers bureau: Honoraries from Novartis, Pfizer, Medac, Ivan Foeldvari: None declared, Christoph Rietschel: None declared, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, MEDAC, Canon, Grant/research support from: Novartis, Pfizer, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell: None declared, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prasad Oommen: None declared, Frank Dressler Speakers bureau: Honoraries from Novartis, Pfizer, Abbvie, Consultant of: Advisory board Novartis, Mylan, Gerd Horneff Speakers bureau: Novartis, Pfizer, Janssen, Grant/research support from: Pfizer, Novartis, Roche, MSD

BackgroundThe cryopyrin-associated periodic fever syndromes (CAPS) are hereditary monogenic autoinflammatory diseases with severe systemic and organ inflammation due to increased production of Interleukin-1β (IL-1β). The subcutaneously administered monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid remission of CAPS symptoms in clinical trials as well as in real-life.ObjectivesThe RELIANCE registry is designed to explore long-term safety and effectiveness of CAN under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA).MethodsThis prospective, non-interventional, observational study with a 3-year follow-up enrolls patients in Germany with clinically confirmed diagnoses of CAPS routinely receiving CAN. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline.Results98 CAPS patients (52% female; 15 [15%] NOMID/CINCA subtypes) were enrolled by December 2021 (Table 1). At baseline, median age was 20 years and median duration of prior CAN treatment was 6 years. At the 36 months visit, 74% of patients reached disease remission by physicians´ assessment along with increasing rates of absent disease activity (patient’s assessment, median 2.0 at baseline and 0.0 month 36). In addition, patients reported low levels of fatigue (absent to mild/moderate: 87% at baseline and 95% at month 36). At baseline, CAPS impaired social life in 47% of patients (37% at month 36) and 33% (23% at month 36) reported days off from school/work. Lab parameters were within normal limits. Remission and disease control were sustained as evaluated parameters remained stable or even decreased over time.Table 1.Patient and physician assessment of clinical CAPS disease activity and laboratory markers over time.Baseline12 months36 monthsNumber of patients, N987240Number (%) of patients in disease remission (physician assessment)64 (68)48 (70)28 (74)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 7)2.0 (0; 7)0.0 (0; 6)Patient’s assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)2.0 (0; 8)1.0 (0; 8)Number (%) of patients without impairment of social life by the disease34 (53)35 (65.0)17 (63)CRP (mg/dl) | SAA (mg/dl); median0.1 | 0.30.1 | 0.50.1 | 0.3Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months36 monthsFever75 (80) | 14 (15)19 (28)4 (11)Fatigue84 (89) | 49 (52)36 (52)17 (46)Conjunctivitis/Uveitis63 (67) | 27 (29)21 (30)7 (19)Headache68 (72) | 30 (32)30 (43)9 (24)Arthralgia/arthritis80 (85) | 32 (34)30 (43)14 (38)Impairment of hearing35 (37) | 23 (25)18 (26)11 (30)Trigger (cold, stress, infections, vaccinations, hormones)71 (76) | 32 (34)21 (30)3 (8)SAENumber of eventsIncidence rate* per 100 patient yearsAll types of SAE | SADR63 | 28#25.98 | 11.55CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse event*Incidence rate = number of events * 36,525 / sum of observation days (=88,558)#Abdominal pain, Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (3 events)ConclusionThe 36-month interim analysis of the RELIANCE study demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Paid instructor for: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Catharina Schuetz: None declared, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Florian Meier Speakers bureau: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

OBJECTIVE Eosinophils are tissue-dwelling immune cells. Accumulating evidence indicates that a type of cell death termed ETosis is an important cell fate involved in the pathophysiology of inflammatory diseases. Although the critical role of eosinophils in eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) is well established, the presence of eosinophil ETosis (EETosis) is poorly understood. We undertook this study to better understand the characteristics of EETosis. METHODS In vitro studies using blood-derived eosinophils were conducted to characterize EETosis. The occurrence of EETosis in tissues from patients with EGPA was studied by immunostaining and electron microscopy. Serum concentrations of eosinophil-derived proteins in healthy controls, patients with asthma, and EGPA patients with active disease or with disease in remission (n = 15 per group) were examined. RESULTS EETosis was reliant on reactive oxygen species and peptidylarginine deiminase type 4-dependent histone citrullination, resulting in the cytolytic release of net-like eosinophil extracellular traps, free galectin-10, and membrane-bound intact granules. The signature of EETosis, including loss of cytoplasmic galectin-10 and deposition of granules, was observed in eosinophils infiltrating various tissues from EGPA patients. Serum eosinophil granule proteins and galectin-10 levels were increased in EGPA and positively correlated with disease activity as assessed by the Birmingham Vasculitis Activity Score (r = 0.8531, P < 0.0001 for galectin-10). When normalized to blood eosinophil counts, this correlation remained for galectin-10 (r = 0.7168, P < 0.0001) but not for granule proteins. Galectin-10 levels in active EGPA positively correlated with serum interleukin-5 levels. CONCLUSION Eosinophils infiltrating diseased tissues in EGPA undergo EETosis. Considering the exclusive expression and large pool of cytoplasmic galectin-10 in eosinophils, elevated serum galectin-10 levels in patients with EGPA might reflect the systemic occurrence of cytolytic EETosis.

Lipid bodies are non-membrane-bound cytoplasmic organelles that are prevalent in mammalian cells of diverse lineages and that have been observed to increase in cells involved in inflammatory responses. Specialized morphological and biochemical studies have provided evidence for the involvement of lipid bodies in eicosanoid synthesis.

BackgroundFamilial Mediterranean Fever (FMF) is a chronic disease characterized by recurrent attacks of fever as well as serositis and bears the risk of serious complications (e. g. amyloidosis). Treatment of FMF according to EULAR aims to control acute attacks and subclinical inflammation as well as to improve patient´s quality of life1. Clinical data indicate that the inhibition of interleukin-1β with canakinumab (CAN) is effective in controlling and preventing flares in FMF patients2.ObjectivesThe present study explores the long-term efficacy and safety of canakinumab in routine clinical practice conditions in pediatric (age ≥2 years) and adult FMF patients.MethodsRELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed FMF diagnosis who routinely receive canakinumab are enrolled in order to evaluate effectiveness and safety of canakinumab. Disease activity and remission by physicians´ assessment, disease activity, fatigue and impact on social life by patients’ assessment, inflammatory markers and AIDAI (Auto-Inflammatory Diseases Activity Index) score were recorded at baseline and assessed at 6-monthly intervals within the 3-year observation period of the study.ResultsThis interim analysis of FMF patients (N=74) enrolled by December 2021 includes baseline as well as 6- to 24-month data. Mean age in this cohort was 25 years (2−61 years) and the proportion of female patients was 51 % (N=38). At baseline, median duration of prior CAN treatment was 1.0 years (0−6 years).At month 24, physician ratings report around 63% of patients in disease remission and patient-reported disease activity (mean PPA) decreased from moderate (3.0) to low (2.6) during the observation period. Other disease activity parameters also decreased (Table 1). A total of 18 serious adverse events were reported, of which 2 (1 case of tonsillectomy and 1 case of tachycardia) were classified as drug - related.Table 1.Baseline characteristics and 4th interim analysis data of patients with FMFBaseline12 months24 monthsNumber of patients, N744624Number (%) of patients with days absent from work/school during last 6 months6 (8)11 (24)9 (38)Number (%) of patients in disease remission (physician assessment)22 (45)23 (72)12 (63)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 10)2.0 (0; 7)2.0 (0; 10)Patient’s assessment of current fatigue; 0–10, median (min; max)5.0 (0; 10)2.0 (0; 10)4.0 (0; 10)Number (%) of patients without impairment of social life by the disease27 (50)28 (80)8 (67)CRP (mg/dl) | SAA (mg/dl) | ESR (mm/h); median0.2 | 0.7 | 8.00.2 | 0.5 | 4.00.2 | 0.7 | 6.0Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months24 monthsFever68 (93) | 14 (29)8 (25)3 (16)Abdominal pain67 (92) | 20 (41)10 (31)4 (21)Thoracic pain45 (62) | 5 (10)3 (9)1 (5)Headache34 (47) | 11 (22)7 (22)5 (26)Myalgia23 (32) | 6 (12)4 (13)2 (11)Arthralgia/arthritis39 (54) | 16 (33)9 (28)5 (26)Dermal symptoms (urticarial, maculopapulose)15 (21) | 5 (10)3 (9)0 (0)SAENumber of eventsIncidence rate# per 100 patient yearsAll types of SAE1814.03SADR21.56Incidence rate = number of events * 36,525 / sum of observation days (=46,848).CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse events.ConclusionInterim data of FMF patients from the RELIANCE study, the longest running real-life canakinumab registry confirm efficacy and safety of long-term canakinumab treatment.References[1]Ozen S, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644–651. doi:10.1136/annrheumdis-2015-208690[2]De Benedetti F, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med 2018;378:1908–19.Disclosure of InterestsJörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Florian Meier Speakers bureau: Novartis, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Frank Weller-Heinemann: None declared, Birgit Kortus-Goetze Consultant of: Novartis, Markus Hufnagel Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Prasad Oommen Grant/research support from: Novartis, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi.

BackgroundThe ProKind Commission of the Society for Paediatric and Adolescent Rheumatology (GKJR) has developed evidence- and consensus-based protocols for the diagnosis and therapy of children and adolescents with defined rheumatic diseases (e.g., [1]). In the ProKind-Rheuma project, it is now investigated whether the protocols are followed in everyday clinical practice and what the treatment-associated outcomes are.ObjectivesTo investigate the mode of treatment and treatment response in patients with polyarticular juvenile idiopathic arthritis (pJIA).MethodsProKind-Rheuma is a multicenter prospective non-interventional observational study. Patients with pJIA enrolled until 17/1/2022 were included into this analysis. Treatments and outcomes up to the 3-month follow-up visit (3FU) were analyzed. Disease states were categorized based on the 2021 cJADAS10 cutoffs [2].ResultsTo date, 18 pediatric rheumatology facilities have participated in ProKind-Rheuma. Data from 203 patients with JIA are available. Of those, 44% have oligoarthritis, 36% polyarthritis, 9% systemic JIA, 6% enthesitis-related arthritis and 3% psoriatic arthritis.In total, 76 patients were diagnosed with pJIA, 38 with already completed 3FU:For 23 patients with pJIA and completed 3FU, we were able to analyze the protocol-defined [1] treatment goal of at least “minimal improvement”. In total, 18 (78%) achieved minimal improvement, 5 (22%) missed it. For 4 of those 5 patients, the underlying MTX therapy was escalated to a bDMARD (3 changed to MTX+bDMARD-combi, 1 to bDMARD-mono). In 3 other patients, therapy was also escalated to an MTX+bDMARD-combi.Between baseline and 3FU, 72% achieved cJADAS10-disease state improvement (Table 1) by at least one category (range 1 - 2), 0% decreased.Table 1.*based on non-missing valuesAt Baseline allAt Baseline with 3FUAt 3FUTotal7638Female, n (%)58 (76)30 (79)Age (years), Mdn (IQR)9 (3-12)7 (2-12)7.5 (3-12)Time since diagnosis (months), Mdn (IQR)0 (0-1)0 (0-1)4 (3-4)RF-positivity, n (%)8 (11)3 (8)Number of active joints (arthritis), Mdn (IQR)7 (4-12)7 (5-12)2 (0-4)JADAS10 (0-40), Mean (SD) (NBL+3FU= 23)18.6 (7.4)19.6 (7.6)7.2 (4.2)cJADAS10 (0-30), Mean (SD) (NBL+3FU= 29)16.3 (5.9)16.7 (6.1)7.1 (4.1)State of inactive disease (cJADAS10≤2.5), n (%*)0 (0)0 (0)4 (13)State of minimal disease activity (2.51 (2)1 (3)9 (28)State of moderate disease activity (533 (54)17 (50)18 (56)State of high disease activity (cJADAS10>16), n (%*)27 (44)16 (47)1 (3)CHAQ (0-3), Mean (SD)0.8 (0.8)0.9 (0.8)0.3 (0.5)Pain (NRS 0 - 10), Mean (SD)4.3 (3)4.7 (3)2.2 (2.7)PedsQL 4.0 total score, Mean (SD)66.3 (22.2)65.4 (21.8)78.4 (17.6)Intraarticular glucocorticoids > 4 joints (ever), n (%)12 (16)5 (13)7 (18)Glucocorticoid pulses (ever), n (%)22 (29)12 (32)13 (34)Methotrexate, n (%)56 (74)31 (82)34 (90)bDMARDs, n (%)7 (9)2 (5)9 (24)Within the first 3 months after diagnosis, the treatment pathways proposed by the ProKind Commission [1] were followed in about three-quarters of patients: i) 5 (13%) received MTX and intra-articular glucocorticoid injections in more than 4 joints (IAGC), but no high-dose intravenous glucocorticoid pulse (HDGC) or bDMARD; ii) 8 (21%) received MTX and HDGC (no bDMARD, no IAGC); iii) 16 (42%) patients received MTX, of whom 4 received a bDMARD up to or at the 3FU (no HDGC, no IAGC). Nine (24%) patients were not treated with MTX or did not fit any of these categories, mostly due to starting bDMARD therapy in conjunction with HDGC or IAGC.ConclusionIn the routine care of JIA patients with polyarthritis, the proposed treatment protocol and treat-to-target strategy are followed in most patients. At 3FU, improvements of JADAS10 and other outcomes were evident, with 41% having achieved inactive or minimal active disease.ProKind is funded by the Innovation Fund “Gemeinsamer Bundesausschuss”, FKZ: 01VSF18031References[1]Horneff et al. Pediatric Rheumatology 2017; 15:78[2]Trincianti et al. Arthritis Rheumatol. 2021 Nov; 73(11):1966-1975AcknowledgementsWe are grateful to all physicians, medical professionals and everyone else who has so far contributed and supported the ProKind-Rheuma project.Moreover, we want to express special gratitude to all patients and their parents for their participation.Disclosure of InterestsSascha Eulert: None declared, Kristina Vollbach: None declared, Klaus Tenbrock: None declared, Jens Klotsche: None declared, Dirk Foell Speakers bureau: Speaker fees/honoraria from Boehringer, Novartis, Werfen and Sobi, Grant/research support from: Novartis and Sobi, Johannes-Peter Haas: None declared, Frank Weller-Heinemann: None declared, Sonja Mrusek: None declared, Prasad Oommen: None declared, Daniel Windschall Speakers bureau: Research support and speakers fee: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Grant/research support from: Research support and speakers fee: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Kirsten Moenkemoeller: None declared, Tilmann Kallinich: None declared, Markus Hufnagel: None declared, Ivan Foeldvari Consultant of: Addvisory board: Hexal, Novartis, Pfizer, Toni Hospach Consultant of: Advisory board: Sobi, Novartis, Moritz Klaas: None declared, Michael Rühlmann: None declared, Ralf Trauzeddel: None declared, Normi Brueck: None declared, Catharina Schütz: None declared, J. B. Kuemmerle-Deschner: None declared, Ariane Klein: None declared, Kirsten Minden Speakers bureau: Speaker: Pfizer, Novartis, Gerd Horneff: None declared

BackgroundIn recent years, transition clinics have been set up at an increasing number of paediatric rheumatology sites in Germany to reduce identified deficits in the care of young people with rheumatic diseases1. In addition, the German Rheumatic Diseases League (Deutsche Rheuma-Liga, DRL), the largest self-help organisation in Germany, has been offering support services for young people in transition since 2016, including the interactive website www.mein-rheuma-wird-erwachsen.de.ObjectivesTo assess the transition competence of young people with juvenile idiopathic arthritis (JIA) and their knowledge of self-help services.MethodsCross-sectional data of the National Paediatric Rheumatology Database (NPRD) from 2016 to 2020 were used to evaluate the health-related transition competence of young people with JIA aged ≥16 years. Health-related knowledge and health-care competence were assessed using a modified self-report instrument2 on a 4-point Likert scale as part of routine documentation in the NPRD. Young people were also asked about their information behaviour and knowledge of new support services. Linear mixed models were used to determine whether health-related transition competence changed between 2016 and 2020, adjusted for disease duration.ResultsDuring the years 2016 to 2020, between 1.908 to 2.536 patients with JIA aged ≥16 years were annually recorded in the NPRD from 56 to 61 paediatric rheumatology sites. The annual patient collectives comprised 34-39% oligoarthritis, 23-26% RF-negative or RF-positive polyarthritis and 22-27% enthesitis-related arthritis cases. In the years from 2016 to 2020, about one-third of patients had inactive disease (cJADAS-10≤1) and about 60% had no functional limitations (CHAQ=0).Over the years, the proportions of patients who rated their disease knowledge and health care competence as “very well” increased significantly in most areas. Although over time, no increase in numbers of patients seeking information about their disease outside of rheumatology consultations were recorded (2016: 22.8%; 2020: 20.9%), awareness of the DRL’s new website for young people with rheumatic diseases increased from 7.7% in 2016 to 26.9% in 2020. Compared to those who were unaware of the new website, those who knew about the website were more likely to have received care in rheumatology settings that offer transition clinics and were more likely to be girls (75% vs 65%), to attend high school (51% vs 46%) and to be slightly older (17.6 vs 17.1 years).ConclusionThe transition competence of young people with JIA seems to have improved over the last five years. During this time, more transition services were made available for young people with rheumatic diseases. However, most young people are not yet aware of these services. Moreover, the effectiveness of the different measures/interventions has yet to be evaluated.References[1]Luque Ramos A et al. Semin Arthritis Rheum 2017;47:269-75.[2]Herrmann-Garitz C et al. Gesundheitswesen 2017;79:491–6.Table 1.Health-related transition competence in JIA patients ≥16 years who participated in the NPRD201620182020p (difference over time)PatientsN=2536N=2068N=1908Disease duration, years6.7±4.97.2±5.07.6±5.1DMARDs at documentation, %576263Disease-related knowledge (best answer “very well”), %N=1992N=1598N=1265name of illness3542420.001names of medicines5459560.717what medicines are for5054520.357who to contact in case of health problems5965650.015influence of smoking, drugs, and alcohol on disease4955540.002how to make a doctor’s appointment6868650.087which doctors are responsible after leaving paediatric care4246490.031Health-care competence (best answer “most of the time”), %N=1784N=1443N=1143inform my doctor of any unusual changes in my health6672690.038keep information about my illness8184840.281ask my own questions5156550.016answer the questions I am asked6973740.014take care of my health concerns and needs6671690.041attend the consultation alone5961610.599speak up for myself and say what I need6468680.537AcknowledgementsThe NPRD has been funded by the Federal Ministry of Health and the companies Abbvie, Chugai, ask, Novartis, PfizerDisclosure of InterestsKirsten Minden Speakers bureau: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Martina Niewerth: None declared, Susanne Schalm: None declared, Ivan Foeldvari: None declared, Johannes-Peter Haas: None declared, Gerd Horneff: None declared, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Grant/research support from: Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Tilmann Kallinich: None declared, Frank Dressler: None declared, Frank Weller-Heinemann: None declared, Rainer Berendes: None declared, Toni Hospach Consultant of: SOBI, Novartis, Markus Hufnagel: None declared, Maria Haller: None declared, Sandra Hansmann: None declared, Jens Klotsche: None declared

BackgroundUveitis is an extra-articular manifestation of Juvenile idiopathic arthritis (JIA) with a prevalence of up to 20% developing most frequently in young girls and patients positive for antinuclear antibodies (ANA). Untreated and uncontrolled uveitis may lead to vision-threatening complications and even blindness.ObjectivesThe main objectives of the analyses were to determine the visual prognosis, uveitis complications and necessity of ocular surgery during the first five years of ocular disease. The likelihood of achieving an inflammation-free phase or even a remission without medication were investigated.MethodsThe Inception Cohort of Newly diagnosed patients with JIA (ICON) was initiated in 2010 in order to prospectively follow JIA patients up to 10 years after JIA disease onset. 953 Patients were assessed at enrollment, three-monthly during the first year, and six-monthly afterwards by a standardized physician’s and patient’s case report form including clinical parameters, treatment data and several laboratory parameters such as ESR, CRP or S100A12. Patients who developed uveitis underwent a regular ophthalmological assessment. The treating ophthalmologist three-monthly completed an additional questionnaire, documenting the anterior chamber (AC) cell grade, current uveitis activity (UA) and UA during the previous three months, best corrected visual acuity (BCVA), uveitis-related complications, previous ocular surgery, current topical treatment and clinical course of uveitis and additional parameters. Inactive uveitis was defined by AC cell grade of 0, quiescence of uveitis by inactive uveitis for at least 6 months, and remission by inactive uveitis for at least 6 months without topical steroids or systemic anti-inflammatory medication (steroids or DMARDs).ResultsA total of 133 children developed uveitis in the JIA disease course, of which 97 patients were documented via the ophthalmological questionnaire for at least two years resulting in a mean follow-up of 5.8 years (SD 1.8). 76% were female, 86% ANA positive, 70% oligoarthritis, and 22% rheumatoid factor negative polyarthritis and mean age at JIA onset was 3.1 (SD 2.1) and uveitis onset at 4.4 (SD 2.2) years. The mean duration between JIA onset and uveitis onset was 15.7 (SD 15.6) months. At least one ocular complication was reported for 24% of patients at first uveitis documentation and 47% of patients had at least one ocular complication until the five year follow-up. Among those, posterior synechiae (31%) and cataract (27%) were the most frequent, followed by an increased IOP (12%) with or without glaucomatous changes. Ocular surgery was rarely necessary, and visual acuity remained quite good in the majority of patients: After five years, >90% had BCVA of ConclusionThe rate of ocular complications is already remarkable at uveitis diagnosis, and increases during uveitis disease course despite anti-inflammatory treatment. However, the visual acuity frequently remains unaffected, and the majority of patients achieve uveitis quiescence and even 40% uveitis remission within 5 years of follow-up.AcknowledgementsThe ICON study is funded by a research grant of the Federal ministry of education and research (BMBF, FKZ 01ER0812, FKZ 01ER1504A-C)Disclosure of InterestsJens Klotsche: None declared, Claudia Sengler: None declared, Frank Dressler: None declared, Dirk Foell: None declared, Ivan Foeldvari: None declared, Johannes-Peter Haas: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Abbvie, Grant/research support from: Pfizer, Novartis, MSD, Chugai, Roche, Abbvie, Toni Hospach Consultant of: SOBI, Novartis, Tilmann Kallinich: None declared, Ina Liedmann: None declared, Kirsten Moenkemoeller: None declared, Martina Niewerth: None declared, Frank Weller-Heinemann: None declared, Daniel Windschall: None declared, Arnd Heiligenhaus: None declared, Kirsten Minden: None declared, Karoline Baquet-Walscheid: None declared