Prospects for Anti-B-Cell Therapy in Immuno-Inflammatory Rheumatic Diseases

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.

Section: Discussionunclassified

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

Каледа¹,

Nikishina²,

Николаева³

et al. 2021

“…В.А. Насоновой» накоплен 10-летний опыт анти-В-клеточной терапии ритуксимабом у пациентов с АНЦА-СВ [38], за последний год приобретен опыт лечения меполизумабом. Представляем результаты анализа течения и исходов COVID-19 у пациентов с АНЦА-СВ, получающих ГИБП (ритуксимаб, меполизумаб), по итогам первых 8 месяцев пандемии COVID-19.…”

Section: The Course and Outcomes Of Covid-19 In Patients With Anca-asunclassified

The course and outcomes of COVID-19 in patients with ANCA-associated systemic vasculitis, receiving biological therapy (Rituximab, Mepolizumab): The results of the first 8 months of the pandemic

Бекетова¹,

Babak²,

Suprun³

2021

Self Cite

Objective. Currently, the issues of the effect of anti-B cell therapy or inhibitor of interleukin 5 on the risk of COVID-19 infecting and outcomes in patients with ANCA-associated vasculitis (AAV) has not been completely studied. We present an analysis of the COVID-19 course and outcomes in AAV patients treated with rituximab or mepolizumab from one rheumatology center registry. Methods. From November 11 to November 15, 2020, a cross-sectional study was conducted using telephone and online surveys, and information was collected from all 128 AAV patients treated with rituximab in V.A. Nasonova Research Institute of Rheumatology. Patients mean age was 51 (20-81) years, 61.7% were women. Granulomatosis with polyangiitis (GPA) was diagnosed in 58 patients, microscopic polyangiitis (MPA)-in 38, eosinophilic granulomatosis with polyangiitis (EGPA)-in 24 (including 54.2% of ANCA-negative cases), and AAV with uncertain nosological affiliationin 8 patients. Due to the disease activity or a high risk of AAV recurrence during the pandemic rituximab was prescribed in 60/126 (47.6%) patients, and mepolizumab-in 6 cases. Results. In the spring of the pandemic (until May 2020), the incidence of COVID-19 in AAV patients treated with rituximab was 4.3%, the disease course was relatively favorable. All patients recovered. At month 3-6, antibodies to SARS-CoV-2 IgG persisted in only 1 out of 4 patients. Since September 2020, the incidence has increased 3-fold, with a more severe course of COVID-19. In total, in the period until November 11, 2020, COVID-19 was diagnosed in 17.2% (22/128); the mean age of patients was 55 (25-81) years; 54.5% were women. 21/22 patients were on rituximab therapy, 2 patients had mepolizumab therapy (including 1 case after previous rituximab therapy). COVID-19 incidence was lower in patients with GPA (15.5%) vs MPA and EGPA (21.1% and 20.8% respectively). The mortality rate was 13.6%, including 2 patients with MPA and 1 patient with GPA. When analyzing the 5-year survival rate according to the registry of AAV patients treated with rituximab, prognosis worsening was noted; in 2020 there were 3 deaths due to COVID-19, in the previous 5 years-only 2 deaths. Discussion. Taking into account the fact the mechanisms of AAV and severe COVID-19 are largely synergistic (primarily in the context of microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome as manifestation of the acute inflammatory syndrome), the activity of AAV can potentially contribute to the disease onset and a severe course of COVID-19. Given the previously published information on the use of rituximab during the COVID-19 pandemic for various diseases, it seems that B cell depletion, without reducing the risk of infection, may have a protective effect with regard to the risk of severe/catastrophic COVID-19, which, however, can be insufficient in AAV patients. Further analysis of COVID-19 cases in patients with AAV and other immuno-inflammatory rheumatic diseases is exceptionally important.

“…К сожалению, терапия ГК сопряжена с высоким риском нежелательных лекарственных реакций (НЛР) и рецидивов заболевания. Поэтому мы разработали комбинированные схемы терапии низкими дозами ГК и цитостатиками (циклофосфамидом) и/или анти-В-клеточным препаратом ритуксимабом (РТМ) для лечения IgG4-СЗ [20,21]. По нашим данным, применение этих схем не уступает в эффективности ГК.…”

Section: шаг 2 критерии исключенияunclassified

The new 2019 American college of rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-related disease

Sokol¹

2020