OBJECTIVES:Juvenile idiopathic arthritis (JIA) in infants is extremely rare, making diagnosis particularly challenging. This study examines the characteristics of JIA in infancy, including early symptoms, time to diagnosis, JIA categories, treatment approaches and clinical outcomes. METHODS:Infants diagnosed with JIA were included in the study if enrolled in the German National Pediatric Rheumatology Database (NPRD) between 2011 and 2020 and followed prospectively. NPRD data were retrospectively supplemented using a dedicated infant-onset JIA module. To analyse differences in disease presentation, the infant-onset cohort was matched with NPRD patients who developed JIA between the ages of >1 and <6 years (toddler-onset JIA). RESULTS:Ninety individuals (62% female) with infant-onset JIA were identified across 18 pediatric rheumatology centres in Germany, with disease onset at 9.5 ± 2.64 months. Compared with toddlers, infants were more frequently affected by systemic JIA. Time from symptom onset to first rheumatology consultation was significantly longer in infants than toddlers (3.1 vs 2.3 months, P = 0.025). At follow-up, disease-modifying anti-rheumatic drugs (DMARDs) were prescribed in 66% of patients with infant-onset JIA and 59% with toddler-onset JIA. Although both groups exhibited similar disease activity at enrolment, the infant-onset group had significantly higher disease activity at follow-up (cJADAS10: 3.0 vs 2.1; P = 0.034). CONCLUSION:Very early-onset JIA is often diagnosed late, delaying appropriate care. Our study underscores the need for improved awareness and earlier recognition of non-infectious arthritis in infants, along with timely initiation of effective treatment to minimize potential long-term consequences.

Zusammenfassung Die medikamentöse Behandlung der juvenilen Psoriasisarthritis und der Enthesitis-assoziierten Arthritis unterscheidet sich teilweise von der anderer Formen der juvenilen idiopathischen Arthritis. Standen bisher vor allem als biologische „disease modifying antirheumatic drugs“ (bDMARD) v. a. Tumornekrosefaktor-α Inhibitoren zur Verfügung, gab es in den letzten Jahren einige vielversprechende Entwicklungen, die teilweise auch die Zulassung in diesen Indikationen erreicht haben. Der Fokus dieses Artikels liegt auf den neueren Biologika – Hemmer von Interleukin (IL) 17 und IL 12/23 bzw. IL23, sowie der small molecules mit Inhibition von Januskinasen, Tyrosinkinase 2 und Phosphodiestase-4 und was bei deren Einsatz zu beachten ist. Der Einsatz der Medikamente bringt für mehr Patienten das Therapieziel Remission in erreichbare Nähe. Register unterstützen beim Erkenntnisgewinn bei der Langzeitbehandlung.

OBJECTIVE:This prospective study assesses the response to canakinumab monotherapy administered as three monthly subcutaneous injections in glucocorticoid-naïve patients with newly diagnosed systemic juvenile idiopathic arthritis (sJIA) and Still disease and evaluates the durability of drug-free inactive disease for up to nine months after canakinumab cessation. METHODS:In a multicenter, two-phase open-label study of newly diagnosed sJIA or Still disease, canakinumab was administered at 4 mg/kg subcutaneously every 4 weeks for 12 weeks. Thereafter, patients were followed for an additional 40 weeks. Routine care was provided to nonresponders. RESULTS:In total, 21 patients were recruited, and 1 was excluded due to protocol violations. Fever resolved immediately in 17/19 patients. Two nonresponders (n = 2) were managed with different strategies: one received steroids alone, and the other received steroids plus canakinumab as part of routine care. By week 12, 14 patients achieved inactive disease. Thereafter, two flares occurred at weeks 24 and 36. Macrophage activation syndrome (MAS) was diagnosed in a third patient at week 19 and responded to treatment with glucocorticoids and cyclosporine A. By week 52, 11 patients had reached drug-free inactive disease and 3 had minimal disease activity. A total of 97 adverse events were reported; four were serious (one MAS, two disease flares, and one viral infection), but none were attributed to the study drug. CONCLUSION:Canakinumab steroid-free first-line therapy in newly diagnosed sJIA induces long-lasting, drug-free inactive disease in a substantial proportion of patients. Discontinuation of canakinumab was associated with disease flares in a minority of patients.

ZUSAMMENFASSUNGMethotrexat (MTX) ist das am meisten verschriebene konventionelle Disease-Modifying Antirheumatic Drug (DMARD). In zahlreichen internationalen Leitlinien für die polyartikuläre juvenile idiopathische Arthritis (pJIA) ist MTX als Erstlinientherapie als Basismedikament empfohlen, trotzdem mangelt es an Konsensus-basierten Empfehlungen zur Verabreichungsform. Diese ist nicht standardisiert und abhängig von der Präferenz des behandelnden Rheumatologen [1, 2]. Insgesamt gibt es nur wenige Publikationen zur Evidenz bzgl. der Applikationsweise von MTX bei der JIA. Die Ergebnisse sind sehr variabel und widersprüchlich, wahrscheinlich bedingt durch sehr unterschiedliche Studiendesigns (retrospektive Registeranalysen, prospektive Beobachtung, prospektive Behandlungsstudie) und überwiegend sehr geringe Fallzahlen [3]. In den letzten Jahren wurden einige größere Studien durchgeführt zum Vergleich der Wirksamkeit von oralem zu subkutanem (s. c.) MTX, jedoch ausschließlich bei Patienten mit rheumatoider Arthritis (RA). In einem kürzlich veröffentlichten Update der aktuellen Literatur zeigt sich keine eindeutige Evidenz, dass die s. c.-Gabe der oralen überlegen ist [4].

Objectives In Germany, canakinumab is approved for the treatment of refractory systemic juvenile idiopathic arthritis (sJIA)/Still’s disease. This study assesses the experience of sJIA/Still’s disease patients treated with canakinumab in clinical practice. Methods Data of 79 sJIA/Still’s disease patients extracted from the BiKeR registry included patients’ and disease characteristics. Three subgroups with disease durations before canakinumab initiation of ≤3 months, >3 to ≤12 months, and >12 months were compared, and 2 with canakinumab as first- and second- or more-line treatment. Results Disease duration was ≤3 months before canakinumab initiation for 26 patients, >3 to ≤12 months for 24 patients, and >12 months for 29 patients. Thirty-nine patients received canakinumab as first-line treatment and 40 as second- or more-line treatment. Disease severity as assessed by the systemic Juvenile Arthritis Disease Activity Score-10 (sJADAS10) was highest for patients with a disease duration <3 months before canakinumab initiation. In the total cohort, after 3, 6, 12, 18, and 24 months, 86%, 81%, 81%, 75%, and 87% of patients reached inactive disease, respectively. Numerically, more patients reached the treatment goal of inactive disease when the disease duration was shorter before initiation of canakinumab. Minimal disease activity (sJADAS10 ≤6.0) did not differ among subgroups. Compared with second-line, more patients with first-line treatment reached inactive disease at months 6, 12, and 24 after canakinumab initiation. sJADAS10 at 12 months correlated significantly with disease duration before treatment. Conclusions Canakinumab treatment led to high improvement rates and achievement of inactive disease state, particularly if they are administered early. Data from clinical practice confirm clinical study data.

Background: Systemic juvenile idiopathic arthritis (sJIA) is characterized by the presence of arthritis and systemic signs and symptoms. In a prospective open label study of early treatment with daily injections of recombinant IL-1Ra in 20 consecutive patients with new-onset sJIA a high response rate could be achieved without corticosteroids and complete discontinuation of IL1 inhibitor therapy was possible in a substantial subset of patients [1]. Objectives: This is a prospective open label study of early treatment with three monthly sq injections of Canakinumab, a recombinant interleukin-1ß monoclonal antibody, in newly diagnosed sJIA (treatment phase). This study is intended to demonstrate high rate of response to monotherapy with Canakinumab not treated with corticosteroids. Primary outcome was response at month 3 defined as steroid-free remission with no fever >38.0°C, no arthritis defined as joint swelling or pain on motion and limited range of motion, normal CRP, no rash, serositis or hepatosplenomegaly attributed to sJIA. In an observation period, the stability of remission off medication in patients treated with Canakinumab, for up to 9 months after treatment will be analysed. Methods: In a multicentre two phase open label unblinded single arm study 20 newly diagnosed sJIA/ juvenile Still’s patients not pretreated with corticosteroids in phase 1 received Canakinumab (4 mg/Kg up to a max of 150 mg s.c. Q4W) for 12 weeks. Before baseline, a short course of 3 days of prednisolone was allowed. Patients with signs of MAS were excluded. In the phase 2, patients will be observed subsequently for at least 40 weeks (9 months). Routine care will be offered to non-responders. Results: 20 patients fulfilling all inclusion criteria but no exclusion criteria were admitted (Table 1). In 18/20 patients fever immediately disappeared. Non responders received routine care off study. 1 additional patient reached inactive disease at month 3 by a single Canakinumab injection and was not furtherly treated due to a probable allergic skin reaction. This patient was excluded from the study. At month 3, 16 patients (80%) reached primary outcome of remission. According to the sJADAS cutoffs, 14 had inactive disease, 3 had minimal disease activity and 1 patient had moderate disease activity (Figure 1). During the observation phase, there were two flares (week 18 and week 36). In a third patient, MAS was diagnosed at week 16 which also was defined as a disease flare. 10 patients already finished the observation phase of the study and 8 had drug free remission. In the total patient cohort, a marked reduction of the sJADAS was observed (Figure 2). 75 adverse events (AE) were reported in 19 of 20 patients. There were 4 serious AE (2 disease flares, 1 MAS and 1 febrile infection), none related to study drug. 1 patient discontinued due to a probable allergic skin reaction. Furthermore, there were 30 infections with 18 upper airway infection seeing the most common infection, 1 cytopenia and two injection site reactions. There were no deaths in this study. Conclusion: Canakinumab first line treatment in newly diagnosed patients with sJIA leads to a high response rate. Few patients did not respond to treatment. After discontinuation of Canakinumab flare occurred in 2/16 patients. One additional patient developed MAS 8 weeks after last injection of Canakinumab which was treated successfully. Steroid-free first line treatment with Canakinumab led to a high response rate and drug free remission in a considerable high rate of patients. The observation is ongoing. REFERENCES: [1] Vastert SJ et al. Arthritis Rheumatol. 2014 Apr;66(4):1034-43.[2] Rosina S et al. Arthritis Rheumatol. 2023; 75 (suppl 9). Acknowledgements: NIL. Disclosure of Interests: Gerd Horneff Novartis, Novartis, Ariane Klein: None declared, Kirsten Minden: None declared, Tilmann Kallinich: None declared, Frank Weller-Heinemann: None declared, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell Novartis, Novartis.

COVID-19 hat die Welt in den letzten 3 Jahren geprägt. Obwohl das Risiko eines schweren Verlaufs bei Kindern gering ist, kann es durch chronische rheumatische Erkrankungen oder die Behandlung mit immunsuppressiven oder immunmodulierenden Medikamenten beeinflusst werden. Das deutsche Register für Biologika in der Kinderrheumatologie (BIKER) erhob bei 68 Zentren systematisch Daten zu Auftreten, Präsentation und Outcome von SARS-CoV-2-Infektionen bei Kindern mit rheumatischen Erkrankungen. Insgesamt 927 SARS-CoV-2-Infektionen bei 884 pädiatrischen Patienten mit rheumatischen Erkrankungen konnten zwischen März 2020 und Dezember 2022 berichtet und analysiert werden. Juvenile idiopathische Arthritis (JIA) war die häufigste Diagnose (716 Infektionen), gefolgt von genetischer Autoinflammation (103 Infektionen), systemischen Autoimmunerkrankungen (78 Infektionen), idiopathischer Uveitis (n = 25) und Vaskulitiden (n = 5). Nur 4 Patienten wurden stationär behandelt. Eine 3½-jährige Patientin verstarb während der 1. Welle an einer Enzephalopathie und Atemstillstand. Die Patientin war wegen einer systemischen JIA mit Methotrexat (MTX) und Steroiden behandelt. Genetische Tests ergaben einen bis dahin unbekannten angeborenen Immundefekt. Kein anderer Patient musste beatmet oder intensivmedizinisch versorgt werden. Es wurde ein Fall von unkompliziertem „pediatric inflammatory multisystem syndrome“ (PIMS) bei einem MTX-behandelten JIA-Patienten gemeldet. Zum Zeitpunkt der Infektion waren über 60

Background: Tocilizumab (TCZ) has been approved for the treatment of polyarticular juvenile idiopathic arthritis (JIA) since 2013. Data on efficacy and tolerability/safety in long-term treatment are scarce. Objectives: To investigate the tolerability/safety of TCZ compared to tumour necrosis factor inhibitors (TNFi) over 36 months, and to analyse the comparative effectiveness of the substances in patients with first and second-line therapies, respectively. Methods: BIKER WA 29358 is a 5-year multi-centre prospective, observational cohort study including patients with polyarticular JIA in Germany starting treatment between 2015 and 2020 with TCZ and matched patients starting an approved TNFi (etanercept, adalimumab or golimumab). Outcomes included JADAS-10-based inactive disease and low disease activity at 12, 24 and 36 months, rates of adverse events (AE) and drug adherence, which were compared between cohorts. Results: Recruitment of 342 participants (TCZ, n=171; TNFi, n=171) was completed over 3 years ago. TCZ was used as 2nd line biologic in the majority of patients (84%), while TNFi were mostly 1st line biologics (86%). Therefore, patients starting on TCZ were older and had a longer disease duration compared to TNFi patients at treatment initiation. At baseline, significantly more patients received TCZ intravenously (72.5%) than subcutaneously (27.5%); this changed over the course of the study (intravenous 43%/subcutaneous 57%). Proportions of patients in TCZ/TNFi treatment groups achieving JADAS inactive disease at 36 months were 86/45% in 1st line biologic users and 57/50% in 2nd line biologic users, in patients still receiving treatment (PPP). At least JADAS low disease activity (LDA) was achieved in 100/68% in 1st line and 77/88% in 2nd line users of TCZ/TNFi (PPP). No significant difference between subcutaneous and intravenous administration was observed regarding rates of patients reaching JADAS inactive disease and JADAS low disease activity (PPP). Safety was assessed based on AE reporting (Table 1): 93 (54%) patients in the TCZ cohort and 102 (60%) patients in the TNFi cohort reported AE during treatment and up to 90 days after treatment discontinuation. The AE rate was similar in both cohorts (65 vs. 57/100 patient years (PY), RR 1.1 (95%CI 0.9-1.4), Wald-test), but rate of serious AE was higher in the TCZ cohort (3.4 vs. 0.5/100 PY; RR 6.4 (95%CI 1.4-29). No opportunistic infection was reported. Cytopenia was more common in the TCZ cohort (13 vs. 1, RR 15.2 (95%CI 2.0-116.3), uveitis and injection site reactions were more common in the TNFi cohort (3 vs. 13/100PY; RR 0.3 (95%CI 0.08-0.95) and 5 vs. 14/100 PY, RR 0.4 (95%CI 0.2-1.2). There was no case of death or malignancy in patients ever exposed to TCZ or TNFi in this cohort. One pregnancy occurred in the TCZ cohort in the follow-up post 90 days after discontinuation of TCZ, with delivery of a healthy child. Two pregnancies were documented in the control cohort: Outcome was delivery of a healthy child in one case and induced abortion in the other. In the TCZ or TNFi cohorts, 92 (54%) vs. 107 (63%) patients discontinued treatment, 49/38 due to lack of efficacy, 27/42 due to remission and 10/11 due to intolerance, respectively. Conclusion: In this interim analysis, treatment targets were reached with similar frequency after 36 months of treatment with TCZ or TNFi. TCZ was used predominantly as 2nd line biologic. Higher rates of remission and minimal disease activity were observed in 1st line compared to 2nd line biologic users. More serious adverse events were reported in the TCZ cohort. No new safety signals were noted so far. Observation is ongoing.Table 1. Patient characteristics, selected reported adverse events (number and rate). REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Ariane Klein: None declared, Angela Zimmer: None declared, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Christiane Reiser speaker honoraria from Novartis and Galapagos., Advisory boards: Pfzer, Sobi, Jasmin B. Kuemmerle-Deschner Novartis and Sobi, Novartis and Sobi, Novartis and Sobi, Maria Fasshauer: None declared, Kirsten Minden: None declared, Ivan Foeldvari: None declared, Christoph Rietschel: None declared, Daniel Windschall Pfizer, Novartis, Abbvie, Medac, Sobi, Canon, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell Novartis, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prassad Thomas Oommen: None declared, Frank Dressler: None declared, Gerd Horneff MSD, Roche, Pfizer, MSD, Roche, Pfizer.Figure 1Treatment goals reached by patients on treatment over 36 months (Rates; 1=100%).

Abstract Background Regular physical activity (PA) has been proven to help prevent non-communicable diseases and is beneficial for disease management in chronically ill populations. Physical inactivity and recreational screen-based media (SBM) use are related to poor health outcomes and common among youth. This study aimed to (1) investigate PA levels and recreational SBM use of adolescents with JIA over time and (2) compare these behaviours with those of their peers. Methods Data from JIA patients and their peers enrolled in the inception cohort study ICON at 11 German centers were analyzed. Individuals aged 13 and over were followed prospectively with questionnaires concerning PA level, recreational SBM use, and health-related quality of life (HRQoL) at a two-year interval. Group by time interactions were analyzed using linear mixed models. Results Data of 214 patients (mean age at first documentation 14.4 ± 0.9 years, female 63%) and 141 peers could be considered. At first documentation, patients were less physically active compared to their peers (p < 0.001). In contrast to their peers, patients’ PA levels increased over time (OR 3.69; 95% CI: 1.01–13.50, p = 0.048). Mean screen time did not differ significantly between patients and peers (first documentation: 3.5 h vs. 3.0 h, p = 0.556; follow-up: 3.6 h vs. 3.3 h, p = 0. 969). During the observation period, male patients reported higher PA levels than female patients, but also higher screen time levels. While low socioeconomic status (SES) (OR 14.40; 95%-CI: 2.84–73.15) and higher cJADAS-10 score (OR 1.31; 95%-CI: 1.03–1.66) increased the likelihood for high SBM use (≥ 4.5 h/d), higher PedsQL psychosocial health score (OR 0.93; 95%-CI: 0.88–0.99) was associated with a decreased likelihood. Conclusions Adolescents with JIA become more physically active over the disease course and achieve comparable levels of PA and recreational screen time to their peers. However, the vast majority appear to be insufficiently physically active. Future interventions to promote healthy lifestyles should include gender and SES as important determinants to reach most vulnerable groups.

Coronavirus disease 2019 (COVID-19) has influenced the world over the last 3 years. Although the risk of a severe course is low in children, it can be influenced by chronic rheumatic diseases or treatment with immunosuppressive drugs or immunomodulatory medication. The German register for biologics in pediatric rheumatology (BIKER) documented systematic data from 68 centers on the occurrence, presentation and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children with rheumatic diseases. Between March 2020 and December 2022, a total of 927 SARS-CoV‑2 infections in 884 patients could be reported and analyzed in pediatric patients with rheumatic diseases. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (716 infections) followed by genetic autoinflammation (103 infections), systemic autoimmune diseases (78 infections), idiopathic uveitis (25 infections) and vasculitis (5 infections). Only four patients were treated as inpatients. A 3.5-year-old female patient died during the first wave from encephalopathy and respiratory failure. The patient was treated with methotrexate (MTX) and steroids for systemic JIA. Genetic tests revealed a previously unknown congenital immune defect. No other patient had to be ventilated or treated on the intensive care unit. A case of uncomplicated pediatric inflammatory multisystem syndrome (PIMS) was registered in a patient with JIA treated with MTX. At the time of the infection over 60% of the patients were treated with standard disease modifying antirheumatic drugs (DMARD) and/or biologics. Although the patients treated with MTX showed a slightly longer duration of symptoms, the antirheumatic treatment did not appear to have a negative influence on the severity or outcome of the SARS-CoV‑2 infection.

ZUSAMMENFASSUNG Die juvenile idiopathische Arthritis (JIA) ist die häufigste chronisch-entzündliche rheumatische Erkrankung des Kindes- und Jugendalters. Mit der Einführung von Biologika konnte eine erhebliche Verbesserung von Prognose, Outcome und allgemeiner Lebensqualität erreicht werden, wobei ein schlechtes Ansprechen auf aktuelle Therapieoptionen bei einem Teil der Patienten die Notwendigkeit von alternativen Therapien unterstreicht. Mit der Zulassung von Januskinase-Inhibitoren, einer neuen Klasse von targeted synthetic Disease-Modifying Antirheumatic Drugs (DMARD), stehen Tofacitinib und Baricitinib aktuell als orale Therapiealternativen bei der JIA zur Verfügung. Erfahrungen aus Studien zur JIA sind begrenzt und können durch die Sammlung und Analyse von Daten aus der klinischen Praxis ergänzt werden. Auch diese sind bislang limitiert. Zur Auswertung stehen die ersten 65 Behandlungen mit Tofacitinib und 20 Patienten mit Baricitinib zur Verfügung. Trotz intensiver Vorbehandlung mit Biologika erreichten unter JAK-Inhibitoren bis zu 75 % der JIA-Patienten eine JADAS-definierte minimale Krankheitsaktivität und 50 % eine inaktive Erkrankung. 13 (20 %) Patienten der Tofacitinib-Kohorte und 1 (5 %) Patient der Baricitinib-Kohorte beendeten die Therapie aufgrund unzureichender Wirksamkeit. Die Verträglichkeit war gut, neue Sicherheitssignale konnten nicht beobachtet werden. Schwere oder opportunistische Infektionen oder thrombembolische Ereignisse wurden bislang nicht beobachtet. Nach den bisherigen limitierten Therapieerfahrungen stellen JAK-Inhibitoren eine bedeutsame Therapiealternative bei der JIA dar. Die Dokumentation wird fortgesetzt.

Background: Canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) older than 2 years of age. Real-world data are rare. Objectives: The aim of the German Biologics Registry (BiKeR) is the surveillance of JIA patients exposed to biologics including Canakinumab. Methods: Baseline demographics and disease activity parameters were documented. Efficacy was determined using the JADAS and the proposed criteria for inactive disease [1]. Safety assessments were based on reports of adverse events (AE). All reports have been coded according to MedDRA ®. Results: 79/345 sJIA patients followed by the BIKER registry were treated with Canakinumab. In 39 patients, Canakinumab was used as first biologic, while 40 patients previously used other biologics (27 were pretreated with one, 12 with two and 2 with one biologic including pre-exposure to Anakinra in 18 patients. Concomitant treatment with steroids and/or methotrexate were given to 29 (37%) and 13 (16%) patients. Patients receiving Canakinumab first line were older (6.1[3.2-11.1] compared to 4.6 [2.5-7.6] years) years but have a shorter disease duration (0.3 [0.1-0.7] years compared to 1.1 [0.5-5.1] years (median [IQR]). First line Canakinumab receivers had more frequently active systemic features (28 [72%] compared to 11 [31%] second-line users) and more often active arthritis (22 [56%] compared to 14 [39%]) while the mean number of active joints was comparable (1.9 +/12.8 vs. 1.9±3.6). First-line Canakinumab receivers showed a significantly higher disease activity reflected by a higher physicians global/parent global/CRP and sJADAS (16.7±8.0 compared to 9.8±8.1) and a higher mean number of active systemic features (2.1±1.3 compared to 0.9±0.9). In the first line cohort, the sJADAS (mean± SD) decreased from 16.7±8.7 to 2.0±3.5 at month 3 and remained low while in the preexposed cohort, the sJADAS decreased from 9.8±8.1 to 2.4±5.5 at month 3. Inactive disease defined as a sJADAS ≤2.9 (ref. 1) was reached at month 3, 6, 12, 18, 24 by 85%/87%/77%/67%/and 100% in first-line Canakinumab patients and by 87%/75%/84%/82% and 79% in biologics pre-exposed patients. A correlation was found between the disease duration before start of Canakinumab and the sJADAS10 at month 6(CC 0.31; p=0.019) and at month 12 (CC 0.246; p=0.06). 197 adverse events (AE) were reported in 57/79 (72%) within 167 patient-years (PY) of exposure to Canakinumab (118 events/100PY). Of these, 33 qualified as serious adverse events (SAE) (20/100PY). Adverse Events of Special Interest were serious and medically important infection (n=7 (4 pneumonias)), cytopenia (n=5), macrophage activation syndrome (n=6), hypersensitivity (n=2; DRESS, urticaria), evolving autoimmune diseases (2; psoriasis and type 1 diabetes mellitus) as well as each one thrombotic event, suicidality and overdose. There were no opportunistic infections, intestinal perforation, bleeding, malignancy, or death. No sJIA associated interstitial lung disease was reported. A total of 58 patients (73%) discontinued treatment, 10 (13%) due to lack or efficacy, 43 (54%) due to remission and 2 (3%) because of intolerance and 3 (4%) for other reasons. Conclusion: Canakinumab demonstrated comparable efficacy if used as first line or second line biologic for treatment of sJIA while a shorter disease duration was associated with a lower sJADAS at month 6 and 12. Safety was comparable and consistent with the overall AE profile of Canakinumab in paediatric patients. MAS as an JIA-associated feature occurred in an expected number of sJIA patients. Infections were the most frequent AE and seven medically important serious infections were reported. No new safety signals specific to the paediatric population were identified for Canakinumab; the risk profile of Canakinumab remains positive for the approved paediatric indication sJIA. REFERENCES: [1] Rosina S et al. Defining Cutoffs for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). Acknowledgements: NIL. Disclosure of Interests: Gerd Horneff MSD, Roche, Pfizer, Toni Hospach: None declared, Tilmann Kallinich: None declared, Frank Dressler: None declared, Frank Weller-Heinemann: None declared, Markus Hufnagel: None declared, Ariane Klein: None declared.

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. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1JADAS-Target inactive disease (≤2.7) in the three strategy-cohorts

Depression is a serious disorder disproportionately affecting people with chronic diseases, yet, to date is rarely recognized comorbidity in pediatric rheumatology clinical routine care. The aim of this study was to investigate the prevalence of depressive symptoms and depression in children with Juvenile idiopathic arthritis (JIA) and to identify associations to risk factors. Depressive symptoms were assessed using the Beck’s Depression Inventory (BDI)-Fast Screen Questionnaire validated for ages 13 and older and confirmed by the BDI or Hamilton Depression Scale. A cross-sectional analysis of 148 patients attending the rheumatology outpatient clinic of the Asklepios Children’s Hospital Sankt Augustin between January 2018 and May 2019 was performed. Possible associations between routinely assessed parameters of disease activity and treatment were analysed. 148 JIA patients (71.5% female), median age 14.7 years, were included. The prevalence for depressive symptoms was 13% and for depression 9.5%, of which 71.4% were newly identified with depression. Significant associations with depressive symptoms included rheumatoid factor negative polyarthritis, higher pain scores, functional limitations, higher disease activity, decreased general well-being, higher number of medications taken and not being in remission. In addition, poor treatment response (persistent pain despite therapy) and failure to achieve minimal activity/remission of disease despite intensified therapy with biologics correlated significantly with depressive symptoms. Depressive symptoms are an important comorbidity in JIA. Early recognition and treatment of psychological distress is essential to prevent deterioration in quality of life and long-term prognosis. Consequently, treat-to-target principles should include mental health as a therapeutic goal.

The efficacy of tumor necrosis factor inhibitors (TNFi) for the treatment of psoriasis is well established, but patients may develop psoriasis for the first time while on TNFi as a paradoxical effect. Limited data on this association in patients with juvenile idiopathic arthritis (JIA) are available. Safety data from patients registered to the German Biologics registry (BiKeR) were analyzed. Patients were grouped by treatment regime: single TNFi, multiple TNFi, non-TNFi biologics or bDMARD-naïve control group receiving methotrexate. TNFi-associated psoriasis was defined as incident diagnosis of psoriasis after starting TNFi treatment. Patients with a history of psoriasis or psoriasis arthritis prior to TNFi therapy were excluded. Event rates using AEs reported after first dose were compared by Wald’s test. A total of 4149 patients were treated with a TNFi (etanercept, adalimumab, golimumab, infliximab), 676 with a non-TNFi biologic (tocilizumab, abatacept, anakinra, canakinumab) and 1692 with methotrexate only. A total of 31 patients were diagnosed with incident psoriasis while on one of the above treatments. Compared with methotrexate, psoriasis was more frequent in the TNFi cohorts (RR 10.8, p = 0.019), specifically in the subgroup of TNF antibodies (RR 29.8, p = 0.0009), whereas no significant signal was observed with etanercept. Also, non-TNFi-treated patients presented high incident psoriasis rates (RR 25.0, p = 0.003). Our findings indicate a higher rate of incident psoriasis in JIA patients treated with TNFi monoclonal antibodies or non-TNFi biologic treatment. JIA patients receiving monoclonal antibody TNFi or non-TNFi bDMARD should be monitored for incident psoriasis. Medication change, if topical skin treatment remains insufficient, may be considered.

Objective: The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development. Methods: Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively. Results: In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher. Conclusions: In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.

Ein 5 Jahre alter Patient stellte sich mit Fieber seit 6 Tagen, Konjunktivitis und Husten vor. Zudem sind ein dunkler Urin und ein entfärbter Stuhl aufgefallen. Die weitere Eigen- und Familienanamnese war unauffällig. Es bestand ein Kawasaki-Syndrom mit begleitendem cholestatischem Ikterus. Eine Therapie mit Acetylsalicylsäure (ASS), hochdosierten intravenösen Immunglobulinen und Kortikosteroiden führte zur Entfieberung und über 7 Wochen zum Rückgang der Cholestase.