LAUSR

Macrophage activation syndrome (MAS) is a severe life-threatening complication of the systemic-onset juvenile idiopathic arthritis (soJIA). The treatment options included high-dose of the corticosteroids (CS), cyclosporine A (CsA), intravenous immunoglobulin (IVIG) and biologics, predominantly IL-1 antagonist – anakinra. In Russia anakinra has not approved yet, so canakinumab (CAN) is a single anti-IL-1 option, available in Russia.To evaluate the safety and efficacy of canakinumab in patients with severe MAS in soJIA, who failed the previous treatment.In the retrospective case series study were included 9 soJIA patients (4 boys and 5 girls) with severe MAS, resistant to combination of high-dose CS, IVIG and CsA.All patients had a MAS during the onset of JIA. The main clinical features of disease onset included: fever 9 (100%), active arthritis 5 (56%), pleuritis 7 (78%), pericarditis – 5 (56%), peritonitis 2 (22%), rash 6 (67%), hepatomegaly 9 (100%), splenomegaly 9 (100%), lymphadenopathy 7 (78%), bleeding 4 (44%), CNS involvement – 3 (33%). Initial treatment included high doses CS 8 (89%), oral CS 9 (100%), methotrexate 5 (56%), tocilizumab 4 (44%), and canakinumab 5 (56%), CsA 4 (44%), IVIG 6 (67%). TCZ was discontinued due to infusion reaction (n=2), TCZ inefficacy (n=3) and presence of MAS in all patients (n=5). In children whom TCZ was switched on CAN we used the standard dose of CAN 4 mg/kg, but if MAS occurred on the CAN we temporally increased the doses since 8 to 25 mg/kg (300 mg). In all cases MAS episodes were successfully resolved during CAN treatment. In 5 (56%) MAS had repeated course during the CAN which lead to temporally increasing the doses of CAN (pt3, pt5, pt8, pt 9) or required to increase immunosupression with abatacept or tofacitinib. Three patients with repeated MAS developed interstitial lung disease (ILD). Two patients who successfully resolved MAS after CAN had relapses of arthritis and switched CAN to TCZ.IDSexJIA onset, yRepeated MASInitial biologicMAS on CANExperience of increased CAN dosesOutcomesCurrent treatment1F7.7NTCZNNRemissionCAN2F11.5NCANNNsoJIA flare, ILDTCZ3F7.9YCANYYRemissionCAN4F3.4NTCZNYRemission, ILDCAN, CS, MMF5M0.8YTCZYYRemission, ILDCAN, abatacept, CsA, CS6M14.2YCANNNRemissionTCZ7M1.1YCANNNRemissionN8М1.3NCANYYRemissionCAN every 12 months9F9.1NTCZYYMinimal disease activityCAN, tofacitinibFootnotes: CAN – canakinumab, CS – corticosteroids, CsA – cyclosporine A, ID – identification, ILD – interstitial lung disease, F – females, M – males, N- no, TCZ – tocilizumab, Y – yes.Canakinumab is an effective rescue treatment either soJIA either MAS. In patients with MAS developed on CAN required the temporal increasing of the doses.This work was supported by the Russian Foundation for Basic Research (grant № 18-515-57001).None declared