Treatment of secondary hemophagocytic syndrome in patients with systemic juvenile idiopathic arthritis. Results of a cohort retrospective study
Authors:   National Medical Research Center of Children's Health, Moscow, Russian Federation, Kriulin I.A. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Alexeeva E.I. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Association of Pediatric Rheumatologists, Moscow, Russian Federation, Shilkrot I.Yu. ,   Association of Pediatric Rheumatologists, Moscow, Russian Federation,   National Association of Non-Governmental Medical Organizations, Moscow, Russian Federation, Dvoryakovskaya T.M. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Association of Pediatric Rheumatologists, Moscow, Russian Federation
Published: January 2023

Secondary hemophagocytic syndrome (SHS) is a life-threatening complication of systemic juvenile idiopathic arthritis (SJIA, syn.: systemic-onset juvenile idiopathic arthritis). Timely treatment of SHS can improve outcomes and reduce mortality rates. There has been little evidence worldwide on the effectiveness of therapy for SHS in patients with SJIA, including the use of genetically engineered biopharmaceutical drugs (GEBDs). Objective. To evaluate the efficacy of different treatment regimens for SHS in patients with SJIA. Patients and methods. This study included 100 patients with SJIA complicated by SHS who were examined and treated at the rheumatology department of the National Medical Research Center for Children’s Health (Moscow) from August 2010 to May 2021. All patients met the criteria for SJIA and SHS diagnosis. The efficacy of different therapy regimens for SHS was assessed according to treatment response criteria and achievement of the clinically inactive status of SHS. The Kaplan-Meier survival analysis was used to investigate the proportion and duration of the period prior to SHS recurrence (relapse-free interval) after the end of therapy, including the use of GEBDs for the treatment of SJIA. The proportion of relapse-free survival cases and the duration of relapse-free interval were assessed within 36 months in 79 of 100 patients (89/114 (78%) SHS cases). Results. Medical records of 100 patients with 114 cases of SHS were retrospectively studied. In 84/114 (73%) cases, SHS developed in patients not receiving GEBDs (“biologically naïve”), and in 30/114 (26%) cases, SHS developed against the background of GEBD therapy (“biologically non-naïve”). Combination therapy, which included intravenous (dexamethasone 17.9 [10; 20] mg/m2/day or methylprednisolone 12.1 [5; 20] mg/kg/day) and oral (prednisolone 0.9 [0.5; 2] mg/kg/day) glucocorticosteroids (GCs), as well as cyclosporine (CsA) at a dose of 4.5 [2; 7] mg/kg/day and normal human immunoglobulin (syn. intravenous immunoglobulin; IVIG) at a dose of 1.5 [0.3; 2] g/kg. In 24/114 (21%) cases, GEBDs were prescribed for the treatment of SHS: in 11 (10%) – tocilizumab, in 8 (7%) – canakinumab, and in 5 (4%) – rituximab. Hemophagocytic syndrome resolved in 111/114 (97%) cases, lethal outcome was registered in 3/114 (3%) cases. Conclusion. Response to treatment and inactive SHS status achievement in the shortest possible time were recorded when using a treatment regimen that included intravenous and oral administration of GCs, as well as CsA and IVIG, regardless of the background use of GEBDs for the treatment of SJIA. In “biologically naïve” patients, response to treatment developed faster, and the proportion and duration of relapse-free interval were significantly greater than in “biologically non-naïve” patients. Key words: secondary hemophagocytic syndrome, systemic juvenile idiopathic arthritis, treatment, genetically engineered biopharmaceutical drugs