Rituximab Biosimilar BCD020 Effectively Treats Pediatric Lupus Nephritis

The rituximab biosimilar, BCD020, was effective in treating pediatric lupus nephritis when previous non-biologic treatment was insufficiently effective, according to a study published in biomedicines.¹ Investigators emphasized future trials assessing the safety and efficacy of rituximab, as well as determining the benefits of the biosimilar compared with conventional systemic lupus erythematosus (SLE) treatment, are required.

Mikhail Kostik, MD, PhD

Credit: ResearchGate.net

“Pediatric lupus nephritis is one of the most serious manifestations of SLE in children, determining the outcomes of the disease,” Mikhail Kostik, MD, PhD, Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Russia, and colleagues. “There are no standardized treatment protocols for pediatric lupus nephritis, and the role of biologics has not yet been conclusively defined.”

Rituximab and belimumab are 2 biologic drugs commonly used to treat SLE. Although it is not officially approved for the treatment of SLE despite its known efficacy, rituximab is prescribed to treat severe, high-activity, life-threatening SLE.²

A retrospective cohort study analyzed the data from 25 pediatric patients with lupus nephritis (10 boys and 15 girls) with a median onset age of 13 (9 – 16) years who failed conventional non-biologic treatment or developed corticosteroid dependence or toxicity. Diagnosis was confirmed via the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria.

The biosimilar BCD020 was given every 2 to 4 weeks at a dosage of 375 mg/m² with repeated courses every 6 to 12 months according to B-cell depletion, disease activity, and immunoglobulin G (IgG) levels. Clinical and laboratory data, corticosteroid doses, and disease activity based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were evaluated at the onset and during the study.

Prior to rituximab biosimilar initiation, non-biologic conventional treatments included pulse therapy of methylprednisolone followed by oral methylprednisolone (n = 25, 100%), cyclophosphamide (n = 15, 60%), hydroxychloroquine (n = 12, 48%), Mycophenolate mofetil (MMF) (n = 8, 32%), and azathioprine (n = 3, 12%). The time before biosimilar initiation was 7.0 months and the observation period was 7.0 months.

Initial treatment pre-rituximab slightly reduced SLEDAI levels and the proportion of pediatric patients with lupus nephritis.

After rituximab administration, patients experienced a reduction of SLEDAI (-60%), C4 complement, proteinuria, hematuria, the anti-double stranded DNA (anti-dsDNA) level (-16%), erythrocyte sedimentation rate (ESR), the proportion of patients not using corticosteroids (-36%), and the median corticosteroid dose by 80% from baseline value.

During the trial, 2 deaths were reported due to catastrophic SLE with macrophage activation syndrome, which was coupled with a severe infection. Additionally, 3 patients reported serious adverse events after the third biosimilar infusion (pneumonia: n = 2; transient agranulocytosis: n = 1) and meningitis after the first infusion. A total of 8 patients received antibacterial treatment for respiratory infections. Most infectious events were reported during the first year of treatment.

Investigators noted that the retrospective nature of the study design, the lack of a unified treatment protocol, missing data, and different classes of lupus nephritis limited the study. Results may have also been affected by changes in treatment, time of initiation, indications for rituximab, and the choice of drug. Severe adverse reaction rate assessment was difficult to determine because of the small sample size coupled with the use of rituximab in pediatric patients with severe catastrophic courses of SLE.

“The implementation of rituximab biosimilar BCD020 therapy allowed for a more effective treatment of SLE patients and the minimization of the side effects of standard therapy,” investigators concluded. “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, for which it is necessary to conduct prospective placebo-controlled trials and compare the effect of rituximab therapy with SOCT, while including a long follow-up observation period.”

References

1. ^{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. Published 2023 May 22. doi:10.3390/biomedicines11051503}
2. ^{Wise, L.M.; Stohl, W. Belimumab and Rituximab in Systemic Lupus Erythematosus: A Tale of Two B Cell-Targeting Agents. Front. Med. 2020, 7, 303.}