What biological drugs are used to treat Systemic Lupus Erythematosus (SLE) in children?

From the Guidelines

Biological drugs such as rituximab and belimumab are used in the treatment of childhood systemic lupus erythematosus (SLE), particularly for severe manifestations or when conventional treatments fail. When considering the treatment of childhood SLE, it is essential to take into account the unique aspects of this population, including dose adjustment, growth, fertility, and psychosocial factors, as highlighted in the kdigo 2024 clinical practice guideline for the management of lupus nephritis 1. Some key points to consider in the treatment of childhood SLE include:

• The use of immunosuppression regimens similar to those used in adults, but with consideration of the specific needs of pediatric patients 1
• The potential for severe disease in the pediatric population, with suggestive evidence that disease is often more severe in this group 1
• The importance of addressing issues such as adherence concerns, growth concerns, fertility concerns, and psychosocial concerns in the treatment plan 1
• The use of biological drugs such as rituximab and belimumab, which target specific immune pathways involved in SLE pathogenesis, and have been shown to be effective in the treatment of severe manifestations of SLE 1. In terms of specific treatment regimens, rituximab and belimumab are commonly used biological drugs in the treatment of childhood SLE, with rituximab typically administered at 375 mg/m² weekly for four weeks or as two 750 mg/m² doses two weeks apart, and belimumab given at 10 mg/kg IV every two weeks for the first three doses, then monthly thereafter, or as a subcutaneous injection of 200 mg weekly 1. It is crucial to individualize treatment duration and monitor disease activity, complete blood counts, and immunoglobulin levels regularly, under the supervision of pediatric rheumatologists, with careful consideration of infection risks and premedication to prevent infusion reactions 1.

From the FDA Drug Label

BENLYSTA is a prescription medicine used to treat: ○ adults and children 5 years of age and older with active systemic lupus erythematosus (SLE or lupus) who are receiving other lupus medicines, and ○ adults and children 5 years of age and older with active lupus nephritis (lupus-related kidney inflammation), who are receiving other lupus medicines

Biological drugs used in childhood SLE:

• Belimumab (BENLYSTA) is used to treat systemic lupus erythematosus (SLE) in children 5 years of age and older.
• Belimumab (BENLYSTA) is used to treat lupus nephritis in children 5 years of age and older.
• The safety and effectiveness of belimumab have been established in pediatric patients 5 to less than 18 years of age for the treatment of SLE and lupus nephritis 2.
• The safety and effectiveness of belimumab have not been established in pediatric patients less than 5 years of age 2.

From the Research

Biological Drugs Used in Childhood SLE

• The use of biological drugs in childhood Systemic Lupus Erythematosus (SLE) has been studied in various research papers 3, 4, 5.
• Belimumab, a B-cell-targeting biologic agent, was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years 3.
• Rituximab may be used for refractory lupus nephritis patients in combination with another Disease-Modifying Antirheumatic Drug (DMARD) 3.
• New therapies targeting CD20, such as atacicept and telitacicept, seem to be promising drugs for SLE patients 3.
• Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial results in phase II randomized control trials in adult SLE patients, and could be alternative treatments for pediatric patients with severe interferon-mediated inflammatory disease in the future 3.

Effectiveness of Biological Drugs

• A randomized controlled trial found that belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy 5.
• The combination of belimumab and rituximab could be developed as a therapeutic strategy for patients with SLE 5.
• Baricitinib and ustekinumab, which have shown positive results in phase II trials with adult SLE, may raise the expectation that these drugs could be beneficial when used in cSLE 6.

Treatment and Management

• The management of cSLE patients includes evaluations of disease activity and cumulative damage scores, routine non-live vaccinations, physical activity, and addressing mental health issues 3.
• Antimalarials and glucocorticoids are still the most common drugs used to treat cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients 3.
• DMARDs should be standardized for each patient, based on disease flare and cSLE severity 3.
• Mycophenolate mofetil or intravenous cyclophosphamide is suggested as induction therapy for lupus nephritis classes III and IV 3.