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<h2>Abstract</h2><h3>Background:</h3> Systemic juvenile idiopathic arthritis (sJIA) is characterized by the presence of arthritis and systemic signs and symptoms, such as daily high spiking fevers, rash, generalized lymphadenopathy, hepatosplenomegaly, and serositis. We conducted a prospective open label study of early treatment with three monthly sq injection of Canakinumab, a recombinant interleukin-1ß monoclonal antibody, in newly diagnosed sJIA (treatment phase). <h3>Objectives:</h3> 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 for up to 9 months after treatment will be analysed. <h3>Methods:</h3> In a multicentre two phase open label unblinded single arm study 20 newly diagnosed sJIA patients. Before baseline, only non-steroidal anti-inflammatory drugs as well as a short course of 3 days of prednisolone but no other treatment were allowed. Patients with signs of MAS were excluded. In phase 1, patients received Canakinumab (4 mg/Kg up to a max of 150 mg sc Q4W) in the 3 months treatment phase. In the observation phase 2, patients will be followed for 40 weeks (9 months). Routine care will be offered to non-responder. sJADAS and cutoffs were calculated [1]. <h3>Results:</h3> 20 patients fulfilling all inclusion criteria but no exclusion criteria were admitted (Table 1). 15 presented with active arthritis, all had active systemic features, 19 had fever, 17 had rash, 6 had serotitis. Upon treatment with Canakinumab in 17/19 patients fever immediately disappeared. Two 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. According to the sJADAS cuttoffs, 13 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. 15 patients completed the observational study phase. 13 patients were in ACR remission without any clinical or laboratory sign of inflammation, 8 had remission off drug > 6 months, 12 had sJADAS inactive disease, 3 had minimal disease activity. None received, corticosteroids, biologics or cDMARDs. In the total patient cohort, a marked reduction of the sJADAS was observed (Figure 2). 96 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 41 infections with 18 upper airway infection seeing the most common infection, and two injection site reactions. According to the protocol, 2 patients had to discontinue study phase 1 due to nonresponse. One presented with polyarthritis, fever and rash, the other with fever, rash, serositis lymphadenitis and splenomegaly but no arthritis. 3 patients discontinued in study phase two due to flare of the disease. All initially presented with arthritis and active systemic features. There were no deaths in this study. Figure 1Patient numbers reaching study targets Figure 2sJADAS10. Patients with a flare are outlined in red. <h3>Conclusion:</h3> This pilot study demonstrated high efficacy of Canakinumab as steroid-free first line treatment in newly diagnosed patients with sJIA with a primary response rate of 90%. According to our protocol treatment was discontinuation after 3 months leading to disease flare in 2 patients. One additional patient developed MAS 8 weeks after last injection of Canakinumab which was treated successfully. Thus, 15 (75%) of newly diagnosed patients with sJIA were efficiently treated with a three month course of Canakinumab only. <h3>REFERENCES:</h3> [1] Rosina S, Rebollo Gimenez A, Tarantola L, Vyzhga Y, Carlini L, Patrone E, Katsikas M, Saad-Magalhaes C, El-Ghoneimy D, El Miedany Y, Khubchandani R, Pal P, Simonini G, Filocamo G, Gattinara M, De Benedetti F, Montin D, Civino A, Alsuweiti M, Stenevicha V, Chasnyk V, Alexeeva E, Al-Mayouf S, Vilayuk S, Pistorio A, Ravelli A. Defining Cutoffs for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score [abstract]. <i>Arthritis Rheumatol.</i> 2023; 75 (suppl 9). https://acrabstracts.org/abstract/defining-cutoffs-for-disease-activity-states-in-systemic-juvenile-idiopathic-arthritis-based-on-the-systemic-juvenile-arthritis-disease-activity-score/. Accessed November 9, 2023 Table 1Patients' characteristics at baselineNo (rate)/ mean±SDN (male gender), n (%)20 (60%)Ethnic_european, n (%)16 (80%)Age, years, mean±SD8.4±4.9Disease duration, months, mean±SD1.2+/ 0.5Pre-treatment with NSAID, n (%)Pre-treatment with oral steroids*Pre-treatment with iv-immunoglobulin15 (75%)3 (15%)2 (10%)joints_painful, mean±SD3.1/-3.4joints_active, mean±SD3.9±4.2Patient global_VAS, mean±SD6.8±1.6Physician global_VAS, mean±SD6.0±1.3Fever, n (%)19 (95%)Rash, n (%)16 (80%)Serositis, n (%)4 (20%)Splenomegaly, n (%)10 (50%)Lymphadenopathy, n (%)7 (35%)No. of systemic manifestations, mean±SD2.8±1.0JADAS10, mean±SD23.9±5.9ESR, mm/h, mean±SD90.5±26.3CRP, mg/l, mean±SD90.2±52.2sJADAS10, mean±SD26.7±5.6*Short course of up to 3 days <h3>Acknowledgements:</h3> <b>NIL</b>. <h3>Disclosure of Interests:</h3> Gerd Horneff UCB, Pfizer, Sobi, Novartis, Ariane Klein: <b>None declared.</b> Tilmann Kallinich: <b>None declared.</b> Kirsten Minden: <b>None declared.</b> Frank Weller-Heinemann: <b>None declared.</b> Ralf Trauzeddel: <b>None declared.</b> Markus Hufnagel: <b>None declared.</b> Dirk Foell: <b>None declared</b>. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.