Lba0008 Effectiveness of Canakinumab for First Line Steroid Free Treatment in Systemic Juvenile Idiopathic Arthritis

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.