Rituximab for rheumatic diseases in children: Results of a retrospective study of the safety of therapy

Abstract

Objective: to analyze the safety of rituximab (RTM) in children with various rheumatic diseases.Materials and methods. The retrospective study included 81 pediatric patients with a confirmed diagnosis of rheumatic disease. Data on the safety of RTM were analyzed for all patients who received at least one infusion of the drug. All patients underwent a standard clinical, laboratory and instrumental examination in accordance with the verified diagnosis before the appointment of RTM therapy. The dose of RTM for administration was calculated based on 375 mg/m 2 of body surface area, the drug was administered once a week for 1 to 4 consecutive weeks, depending on the number of CD19 lymphocytes determined after the infusion, and the tolerability of therapy.Results. Among the patients included in the study, 38 (46.9%) were with systemic lupus erythematosus (SLE), 16 (19.75%) – with juvenile idiopathic arthritis (JIA), polyarticular variant (14 (87,5%) of them – RF-positive), 9 (11,1%) – with juvenile idiopathic arthritis with systemic onset (sJIA), 6 (7.4%) – with systemic sclerosus (SSc), 5 (6.2%) – with primary Sjogren’s syndrome, 2 (2.5%) – with juvenile dermatomyositis, 4 (4.9%) – with mixed connective tissue disease, and 1 – with livedoid vasculopathy. 53 (65.4%) patients underwent more than one course of RTM therapy, with a maximum of 10 courses. The total number of infusions was 198. The median time between each course was 182 [156–315] days. RTM was effective in 67 (95%) patients, ineffective in 2 (2.5%) patients with sJIA, 2 (2.5%) patients with SLE and macrophage activation syndrome (MAS).Adverse reactions (AE) of mild to moderate severity were reported in 23 (28.4%) patients, including upper respiratory tract infections – in 7 (8.6%), urinary tract infections – in 2 (2.5%), mild infusion reactions that did not require discontinuation of therapy – in 2 (2.5%), clinically insignificant neutropenia (I–II degree) – in 4 (4.9%), a decrease in IgG levels – in 14 (17.5%) patients (median – 5.5 [4.0; 6.9] g/l). Two patients with sJIA had persistent hypogammaglobulinemia for 3 and 5 years after the last RTM infusion, respectively. The incidence of infections in patients with low IgG levels was 35.7%, and no cases were registered in patients with neutropenia. Serious AE was reported in 16 (19.7%) patients: sepsis – in 4 (4.9%), pneumonia – in 3 (3.7%), herpes zoster – in 1 (1.2%), serious infusion reactions – in 2 (2.5%), serious postinfusion reactions within 3–10 days – in 4 (4.9%) (in 3 patients (3.7%) – MAS, in 1 (1.2%) – hemorrhagic vasculitis); death was registered in 2 cases of SLE and MAS (therapy of RTM was inefficient). In general, various AE were reported in 55.6% of patients with sJIA, 52.6% of patients with SLE, 50% of patients with SSc and juvenile dermatomyositis, and 80% of patients with primary Sjogren’s syndrome. Discontinuation of therapy due to serious AE was observed in 15 (18.5%) patients.Conclusion. Our study demonstrated that RTM therapy is highly effective with an acceptable safety profile in children with rheumatic diseases. The safety data obtained indicate the need for careful monitoring of therapy, primarily taking into account the risk of infection, despite the fact that in this study the frequency of infectious complications was not high. A decrease in IgG level was observed in a small proportion of patients and did not correlate with the incidence of infections.

Keywords

• rituximab
• adverse reactions
• immune-mediated rheumatic diseases