Rituximab Biosimilar Found Effective in Pediatric Patients With Lupus Nephritis

A retrospective cohort analysis published in Biomedicines found that a rituximab biosimilar, BCD-020, was effective and tolerable in pediatric patients with lupus nephritis, a kidney disease caused by systemic lupus erythematosus (SLE).

“The implementation of rituximab biosimilar BCD-020 therapy allowed for a more effective treatment of SLE patients and the minimization of the side effects of standard therapy. It is necessary to evaluate the effectiveness of rituximab not only as a rescue treatment in cases of severe courses of SLE and the failure of standard therapy, but also as a remission induction tool in forms of SLE that are not only severe but also moderate [disease],” wrote the authors.

Pediatric lupus nephritis is one of the most serious conditions that can result from SLE in children. There is no standardized treatment guideline for pediatric lupus nephritis, and belimumab, a common treatment for the disease in adults, is only approved for patients over 5 years of age. Although the use of biologics has significantly changed the treatment landscape for many rheumatic diseases, the role biologic drugs can play in treatment for pediatric lupus nephritis has not been clearly defined.

BCD-020, also known as AcellBia, is the first Russian rituximab biosimilar approved for medical use in lymphoma patients in Russia and some Commonwealth of Independent States countries. The biosimilar was developed by Biocad CJSC. It references Rituxan (rituximab), which is FDA-approved to treat rheumatoid arthritis, CD20-positive B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, microscopic polyangiitis and granulomatosis with polyangiitis, and pemphigus vulgaris.

The researchers collected data from the case histories of 25 pediatric patients (n = 10 boys and 15 girls) with lupus nephritis who failed conventional non-biologic treatment or developed corticosteroid dependence/toxicity from 2 centers between 2014 and 2021. The average age of disease onset was 13 years (range, 9-16). The diagnoses were made using the Systemic Lupus International Collaborating Clinics classification criteria.

During the evaluation period, patients were prescribed BCD-020 at a dosage of 375 mg/m² each week for 2 to 4 infusion sessions. The treatment course was repeated every 6 to 12 months according to disease activity, B-cell depletion, and immunoglobulin G levels.

The conventional therapies used to treat the patients prior to receiving the rituximab biosimilar were cyclophosphamide (n = 15; 60%), mycophenolate mofetil (n = 8; 32%), azathioprine (n = 3; 12%), hydroxychloroquine (n = 12; 48%), and pulse therapy of methylprednisolone followed by oral methylprednisolone (n = 25; 100%). Changes in disease outcomes from baseline were measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Rituximab treatment initially reduced SLEDAI levels slightly and the proportion of patients with lupus nephritis. During treatment, the researchers observed significant reductions (80%) in SLEDAI, the anti–double-stranded DNA level, proteinuria, hematuria, C4 complement, erythrocyte sedimentation rate, and the median corticosteroid dose needed by patients from baseline. Additionally, the proportion of patients without corticosteroids was reduced after rituximab administration.

Two deaths were observed as a result of catastrophic SLE with macrophage activation syndrome, accompanied by a severe infection (invasive aspergillosis, n = 2). Three patients experienced severe adverse events, including pneumonia (n = 2) and transient agranulocytosis (n = 1) after the third rituximab infusion.

One patient developed meningitis, which was caused by Listeria moncytosis and was observed after the first rituximab infusion. This patient received 2 additional rituximab courses 8 months after recovering and did not experience any follow-up adverse events. Overall, 8 patients received antibacterial treatment for respiratory infections without hospital admission.

The limitations of the study were attributed to the retrospective nature of the study as well as missing data, a lack of unified treatment protocol, and different lupus nephritis classes of patients. Additionally, assessing the real extent of serious adverse events was difficult due to the small sample size of the study.

"The implementation of rituximab biosimilar BCD-020 therapy allowed for a more effective treatment of SLE patients and the minimization of the side effects of standard therapy," the authors concluded, but also noted that randomized controlled trails are required to further confirm the safety and efficacy of rituximab in this population and evaluate the benefits when compared with conventional therapy for SLE. They also recommended a long follow-up observation period to accurately evaluate the long-term safety of rituximab in pediatric patients with lupus nephritis.

Reference

Kostik M, Kalashnikova E, Rinat R, et al. Rituximab biosimilar BCD020 shows superior efficacy above conventional non-biologics treatment in pediatric lupus nephritis: the data of retrospective cohort study. Biomedicines. 2023; 11(5):1503. doi:10.3390/biomedicines11051503