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BACKGROUND: Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. AIM: To compare the benefits of RTX above SOCT. METHODS: The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. RESULTS: Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. CONCLUSION: RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.
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BACKGROUND: Pediatric lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) in children, determining the outcomes of the disease. There are no standardized treatment protocols for pediatric LN, and the role of biologics has not yet been conclusively defined. OBJECTIVES: analyze the safety and efficacy of rituximab biosimilar BCD020 in pediatric patients with lupus nephritis. METHODS: in a retrospective cohort study, the data from the case histories of 25 patients with LN (10 boys and 15 girls) with an onset age of 13 (9-16) years, who failed conventional non-biologic treatment or developed corticosteroid dependence/toxicity, were included. The diagnosis was made using Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. Rituximab biosimilar BCD020 was prescribed in a dosage of 375 mg/m2 every week (2-4 infusions) with repeated courses every 6-12 months (2-4 infusions) according to disease activity, B-cell depletion, and IgG levels. The dynamics of clinical and laboratory data, the activity of the disease by SLEDAI, and corticosteroid doses were assessed at the onset and during the rituximab trial. RESULTS: The main patient's characteristics were: Pre-rituximab non-biologic conventional treatment included: cyclophosphamide 15 (60%), MMF 8 (32%), azathioprine 3 (12%), hydroxychloroquine 12 (48%), and pulse therapy of methylprednisolone followed by oral methylprednisolone 25 (100%). The time before rituximab was 7.0 (3.0-24.0) months, and the whole observation period was 7.0 (0; 24) months. The initial pre-rituximab treatment slightly reduced SLEDAI levels and the proportion of patients with LN. A significant reduction of SLEDAI, the anti-dsDNA level, proteinuria, hematuria, C4 complement, ESR, and the median corticosteroid dose by 80% from the initial value, as well as the proportion of patients without corticosteroids, was observed after rituximab administration. Two deaths were observed due to catastrophic SLE with macrophage activation syndrome, accompanied by a severe infection (invasive aspergillosis, n = 2). Three patients developed serious adverse events: pneumonia (n = 2), transient agranulocytosis (n = 1) after the third rituximab infusion, and meningitis, caused by Listeria monocytosis, after the first rituximab infusion. Eight patients received antibacterial treatment for different respiratory infections without hospital admissions. CONCLUSIONS: Rituximab biosimilar BCD020 showed effectiveness in LN, whereas previous non-biologic treatment was insufficiently effective. Randomized controlled trials are required to evaluate the efficacy and safety of rituximab and evaluate the benefits when compared with conventional SLE treatment.
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Objectives: To describe the clinical characteristics of hip involvement in juvenile idiopathic arthritis (JIA) from arthritis to hip osteoarthritis (HOA) and total hip arthroplasty (THA). Study Design: Seven hundred fifty-three patients aged 2-17 years with JIA were included in the study. The comparison analysis was performed between the following subgroups: (i) JIA without hip involvement (n = 600; 79.7%) vs. JIA with hip involvement without HOA (n = 105; 13.9%), (ii) JIA with hip involvement with HOA, but without THA (n = 32; 4.3%) and JIA with hip involvement with HOA and with THA (n = 16; 2.1%). Clinical, laboratory characteristics and treatment regimens compared. Results: Hip involvement was present in 20.3% of patients. HOA was present in 6.4% (12*1,000 patient-years) of the entire JIA group and 31.4% of patients with hip involvement. Sixteen patients (2.1%; 4.0*1,000 patient-years) required THA. The following factors were associated with HOA: sJIA (OR = 3.6, p = 0.008; HR = 3.0, p = 0.002), delayed remission (OR = 4.2, p = 0.004; HR = 1.4, p = 0.538), delay in biologic therapy initiation (OR = 7.5, p = 0.00001; HR = 6.7, p = 0.002), alkaline phosphatase <165 U\l (OR = 4.1, p = 0.0003; HR = 5.2, p = 0.000004), treatment with corticosteroids (CS) (OR = 2.6, p = 0.008; HR = 1.2, p = 0.670), cumulative corticosteroids >2,700 mg (OR = 4.3, p = 0.032; HR = 1.4, p = 0.527). The following factors were associated with THA: delay in biologic treatment initiation (OR = 1.04, p = 0.0001; HR = 9.1, p = 0.034), delayed hip involvement (OR = 5.2, p = 0.002; HR = 3.0, p = 0.044), and methylprednisolone pulse therapy (OR = 10.8, p = 0.0000001; HR = 5.6, p = 0.002). Conclusion: Both sJIA and systemic CS, impaired calcium-phosphorus metabolism, and delayed hip arthritis are associated with HOA development in JIA. HOA is considered to be a severe adverse event of CS treatment, especially delayed hip involvement.
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BACKGROUND: Immunosuppressive drugs, incomplete vaccine coverage, immune system dysregulation might be factors of a low level of anti-vaccine antibodies in JIA patients. The study aimed to evaluate vaccine coverage, post-vaccine immunity, and risk factors of non-protective levels of antibodies against measles, mumps, rubella, hepatitis B, and diphtheria in JIA patients. METHODS: A cross-sectional study included 170 children diagnosed with JIA aged 2 to 17 years who received routine vaccinations against measles, rubella, mumps (MMR), diphtheria, and hepatitis B national vaccine schedule. In all patients, the levels of post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B, and diphtheria were measured with ELISA. RESULTS: Protective level of antibodies were 50% against hepatitis B, 52% - diphtheria, 58% - measles, 80% - mumps, 98% rubella. MMR's best coverage had patients with enthesitis-related arthritis-85%, compared to oligoarthritis-70%, polyarthritis-69%, systemic arthritis-63%. Diphtheria coverage was 50, 51, 46, 63%, respectively. Incomplete MMR vaccination had 39% patients, treated with biologics, 22% with methotrexate and 14% with NSAID (p = 0.025), and 61, 46, 36% for diphtheria (p = 0.021). Incomplete vaccination was a risk factor of non-protective level of antibodies against measles (HR = 2.03 [95%CI: 1.02; 4.0], p = 0.042), mumps (HR = 6.25 [95%CI: 2.13; 17.9], p = 0.0008) and diphtheria (HR = 2.39 [95%CI: 1.18; 4.85], p = 0.016) vaccines, as well as JIA category, biologics, corticosteroids and long-term methotrexate treatment for distinct vaccines. One-third part of JIA patients continued vaccination against MMR and diphtheria without serious adverse events and JIA flare. There were no differences between patients who continued MMR vaccination or denied in the means of JIA category and treatment options. Patients, continued diphtheria vaccination rare received methotrexate (p = 0.02), biologics (p = 0.004), but had higher levels of anti-diphtheria antibodies (p = 0.024) compare who omitted vaccination. Methotrexate (OR = 9.5 [95%CI: 1.004; 90.3]) and biologics (OR = 4.4 [95%CI: 1.6; 12.1]) were predictors of omitted diphtheria revaccination. CONCLUSION: Children with JIA may have lower anti-vaccine antibody levels and required routine checks, especially in children with incomplete vaccination, biologics, systemic arthritis, and long-term methotrexate treatment. Revaccination of JIA patients was safe and effective.
