Prof. Hess Kinderklinik

Background:Associated uveitis is common among patients with juvenile idiopathic arthritis and carries a risk of long-term damage to the eye and vision [1]. Data out of clinical practice regarding the occurrence of uveitis during therapy are limited.Objectives:Comparison of the occurrence of uveitis and uveitis flares under therapy with three different TNF inhibitors using the BIKER-registry.Methods:Baseline demographic characteristics, clinical and laboratory conditions as well as the occurrence of uveitis and uveitis flares during therapy with either Etanercept, Adalimumab or Golimumab were compared.Results:3315 JIA patients treated with one of the TNF inhibitors etanercept (n=2121), adalimumab (n=963 patients) or golimumab (n=231 patients) were analyzed for the occurrence of first uveitis or uveitis recurrence. The cohorts differed significantly regarding the distribution of JIA subtype (p<0.0002), the rate of ANA-positive patients treated with etanercept was significantly lower than the ones treated with adalimumab or golimumab (57.8% vs 67.6%/66.5%, p<0. 0001), there were significant differences in age at disease onset (etanercept-cohort patients oldest, 7.4 years vs 6.36/5.5 years adalimumab/golimumab; p<0.0001), while age at therapy start was highest in the golimumab cohort, these patients were significantly older than in the etanercept cohort (12.63 vs 11.6, p=0.0001). The groups differed significantly regarding the CHAQ-DI (etanercept 0.65 vs 0.48/0.46 adalimumab/golimumab, p<0.0001), the JADAS (etanercept 15.1 vs 11.2/11.1 adalimumab/golimumab, p<0.0001), CRP and ESR (both significantly higher in the etanercept cohort than in the adalimumab/golimumab cohort, p=0.0001).Concomitant therapy with steroids was used significantly more often in the etanercept cohort than in the other two groups (33.4% vs. 24.4/16%, p<0.0001), MTX was applied significantly less in the adalimumab cohort than in the etanercept and golimumab cohort (64% vs. 72% each, p<0.0001). There were significant differences in pre-treatment with other biologics, in the etanercept cohort 5.6% of the patients were pre-treated with biologics, in the adalimumab cohort 58.3% and in the golimumab cohort 78.4% (p<0.0001).Uveitis before start of treatment was significantly more frequent in the adalimumab and golimumab cohort than in the etanercept cohort (approx. 30% vs. 6.7%, p<0.0001). Uveitis recurrence also differed significantly, occurring most often and earlier (Figure 1A) in the golimumab cohort in approximately 36% of patients with preexisting uveitis, while it was documented in approx. 23% upon adalimumab and in 19% upon etanercept (p=0.02). The rates were 30.5 vs. 10 vs 7.7 events/100PY in the golimumab vs adalimumab vs etanercept cohort (p<0.0007). The first occurrence of uveitis during ongoing therapy did not differ significantly between the cohorts (Figure 1B).Conclusion:Pre-existing uveitis increases the risk of recurrence compared to the probability of developing first uveitis during treatment. Etanercept is used less frequently in patients with a preexisting uveitis. Adalimumab is often used as first-line biologic therapy for uveitis, so the rate of pre-existing uveitis in this group should be evaluated accordingly in the interpretation. Recurrence of uveitis is significantly more frequent with golimumab than with etanercept or adalimumab. While golimumab is used as a second-line or third-line biologic in almost 80% of cases; the previous treatment refractory status including uveitis of the patients is a bias which should be taken into account when evaluating the data. The results have to be interpreted carefully due to significant differences in baseline parameters. Observation is ongoing.REFERENCES:[1] Foeldvari I, Becker I, Horneff G. Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry. Arthritis Care Res (Hoboken). 2015 Nov;67(11):1529-35. doi: 10.1002/acr.22613. PMID: 25988824.Acknowledgements:This study would not have been possible without the collaboration of numerous German and Austrian paediatric rheumatologists, patients and their parentsDisclosure of Interests:Carolin Baucks: None declared, Angela Zimmer: None declared, Toni Hospach: None declared, Daniel Windschall: None declared, Kirsten Minden: None declared, Frank Weller-Heinemann: None declared, Ivan Foeldvari: None declared, Gerd Horneff Pfizer Chugai, Novartis, MSD, Pfizer, Roche, MSD, Novartis.

Background:National and international guidelines call for rapid and effective therapy with the aim of achieving an inflammation-free clinical condition as quickly as possible. Nevertheless, the prognosis of many patients remains uncertain, so that an optimisation of the care situation appears necessary.Objectives:Improvement and harmonisation of diagnosis, monitoring, treatment decision and prognosis is the aim of the PROKIND protocols [1].Methods:Prospective treat-to-target observational study of patients with polyarticular JIA during the first year of treatment according to the PROKIND recommendations [1]. Acceptability and outcomes of different treatment pathways with treat-to-target strategy for polyarticular JIA are investigated in the GBA-funded project. Patients with initial therapy with methotrexate form cohort 1, patients with additional repeated intravenous corticosteroid pulse therapy form cohort 2, patients with concomitant intra-articular corticosteroid application in at least 5 joints or multiply repeated injections form cohort 3. According to the step up T2T protocol, biologics are added if targets were not reached [1].Results:160 pJIA patients (RF+ polyarthritis n=24, RF- polyarthritis n=138, unknown RF status n=8) from 23 paediatric rheumatology institutions in Germany and Austria were recruited, 86/53/31 patients were assigned to cohort 1/2/3. Patients of cohort 2 had higher disease activity (JADAs10), higher functional limitations (CHADQ-DI) and higher CRP and ESR (Table 1). The mean JADAS10 showed a decrease in disease activity from 19.2±7.7 at baseline to 3.5±4.6 at month 12, the decrease in CHAQ-DI from 0.9±0.8 to 0.3±0.5 showed improvement in functional capacity. Similarly, improvements in quality of life, pain and fatique were demonstrable. JADAS-inactive disease was achieved by 20.8% at month 3, 42.1% at month 6 and 57.7% at month 12. Escalation to biologic-based therapy was received by 40/86 (47%) of patients in cohort 1 (MTX only), 25/53 (47%) in cohort 2 (MTX+steroid pulses), and 14/31 (45%) in cohort 3 (MTX+extensive i.a. steroids).Treatment escalation to second biologic was used in 10%/9%/10%. Finally, in cohort 1/2/3. A total of 60.4%/48.5% and 66.7.2% had a JADAS inactive disease (JADAS10≤ 2.7) and an additional 25.0%/24.2%/20.8% had a minimal disease activity (JADAS 10 2.8-≤6) and 14.6%/24.2%/12.5 had residual moderate disease activity (JADAS10 6.1-≤17) while only 1 had high disease activity.Conclusion:A treat-to-target approach achieves dramatic improvement in disease activity in polyarticular juvenile idiopathic arthritis. Already after 12 months, in about two thirds of patients inactive disease was achieved with marked improvement in functional limitations and quality of life. However, an additional benefit of repeated steroid pulse therapy or extensive intra-articular steroid injections was not recognizable. Due to the study design data must be interpreted with caution.REFERENCES:[1] Horneff G, Klein A, Ganser G, Sailer-Höck M, Günther A, Foeldvari I, Weller-Heinemann F. Protocols on classification, monitoring and therapy in children’s rheumatology (PROKIND): results of the working group Polyarticular juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2017 Nov 7;15(1):78. doi: 10.1186/s12969-017-0206-9. PMID: 29116003; PMCID: PMC5678777.Figure 1.JADAS-Target inactive disease (≤2.7) in the three strategy-cohortsAcknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundCAPS (Cryopyrin-associated periodic fever syndromes) are monogenic autoinflammatory diseases causing great burden to patients due to severe systemic and organ inflammation caused by increased production of interleukin-1β (IL-1β). In clinical trials as well as in real-life, the monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid suppression of CAPS symptoms.ObjectivesThe RELIANCE registry explores 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 enrolls patients with clinically confirmed diagnoses of CAPS routinely receiving CAN. Clinical data, physician assessments and patient-reported outcomes are evaluated in 6-monthly intervals.Results107 CAPS patients (53% female; 16% NOMID/CINCA subtypes) were enrolled by December 2022. At baseline, median age was 23 years and median duration of prior CAN treatment was 6 years. 92% of patients received greater than standard dose CAN.75% of the patients were in disease remission at month 48 by physician assessment. Patients report stable low level disease activity (median 2.0 at baseline and 1.5 at month 48) and fatigue (median 3.0 at baseline and 1.0 at month 48). No relevant differences regarding subtype severity were observed (Table 1). At baseline vs. month 48, 46% vs. 50% of patients experienced impairment of social life and 32% vs. 25% reported days off from school or work due to the disease.Severe adverse events (SAE) suspected to be drug-related were reported for N=9 (8.4%) CAPS patients. The incidence rate (IR) per 100 patient-years kept stable over time.ConclusionThe 48-month interim analysis of the RELIANCE registry demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity.Table 1.Assessment of clinical CAPS disease activity and laboratory markers over time.Baseline24 months48 monthsNOMID/CINCAMWS, FCASNOMID/ CINCAMWS, FCASNOMID/ CINCAMWS, FCASNumber* of patients, N17801054313Number (%**) of patients with days absent from work/school during last 6 months6 (35)25 (32)2 (20)20 (37)0 (0)4 (31)Number (%**) of patients in disease remission (physician assessment)13 (77)53 (68)8 (80)33 (61)2 (67)10 (77)Patient’s assessment of current disease activity; 0–10, median (min; max)1.0 (0; 7)2.0 (0; 7)2.0 (0; 4)1.0 (0; 8)0.0 (0; 0)2.0 (0; 5)Patient’s assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)3.0 (0; 9)2.0 (0; 7)2.0 (0; 9)0.0 (0; 0)1.0 (0; 7)Number (%**) of patients without impairment of social life by the disease5 (56)29 (57)3 (50)25 (63)0 (0)2 (67)Current influence of the disease on mood; % of patients** with negative | positive | no influence30 | 10 | 6023 | 19 | 5917 | 33 | 5024 | 37 | 400 | 0 | 025 | 25 | 50CRP, median (mg/dl)0.20.10.30.20.90.1SAA, median (mg/dl)0.40.40.90.40.60.2ESR, median (mm/h)6.05.08.05.05.02.5SAENumber of eventsIR‡ per 100 patient-yearsAll types of SAE6522.85SADR28#9.84NOMID/CINCA00MWS/FACS2611.55# 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 discolouration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (N=3 events)*subtype not reported for all patients.**not reported for all patients.‡IR = number of events * 36525/ sum of observation days (=103905)CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A; SADR, serious adverse drug reactionREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Consultant of: Novartis, Catharina Schuetz Grant/research support from: 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, Frank Weller-Heinemann: None declared, Tilmann Kallinich Speakers bureau: Roche, Anne Pankow: 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, Peter Wasiliew Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Michael Fiene: None declared, Florian Meier Speakers bureau: Novartis, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Ioana Andreica Speakers bureau: Abbvie, Chugai, Novartis, UCB, MSD, Lilly, Sobi, Astrazeneca, Amgen, Pfizer, Gilead, Paid instructor for: Astrazeneca, UCB; Consultant Abbvie, Chugai, Novartis, UCB, Galapagos, Takeda, Astrazeneca, Lilly, Boehringer Ingelheim, Amgen, Sobi, 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

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.

Abstract 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 till March 2019, and baseline characteristics, effectiveness, as well as 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, as well as ACR-inactive disease definition. Safety assessments were based on adverse events (AE) reports. Results: 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 9 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, 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. Keywords: Juvenile idiopathic arthritis, JIA-treatment, etanercept, TNF-inhibitors, biologics registry, drug surveillance

Abstract 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 till March 2019, and baseline characteristics, effectiveness, as well as 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, as well as ACR-inactive disease definition. Safety assessments were based on adverse events (AE) reports. Results: 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 9 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, 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. Keywords: Juvenile idiopathic arthritis, JIA-treatment, etanercept, TNF-inhibitors, biologics registry, drug surveillance