Updates in Pediatric Lupus: Experts Discuss Advances in Lupus Nephritis Treatments, Monogenic Lupus & More

Other options: Targeted B cell therapy has also recently shown some promise. Dr. Jackson highlighted recent research on belimumab and newer anti-CD20 agents. Belimumab is a monoclonal antibody that targets B cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). In clinical trials, belimumab showed modest—but statistically significant—improvement in renal outcomes when added to baseline immunosuppression.³ In December 2020, it became the first drug approved by the FDA to treat adults with lupus nephritis. Intravenous belimumab is also FDA approved to treat children older than 5 with systemic lupus erythematosus who are receiving standard care.

Another potential method of targeting B cells is through B cell depletion with anti-CD20 agents, such as rituximab. In a previous large clinical trial, rituximab failed to show a benefit in lupus nephritis.⁴ However, Dr. Jackson suggested this may be due to incomplete B cell depletion with rituximab. Newer anti-CD20 agents, such as obinutuzumab, have enhanced B cell depletion and may prove viable therapeutic options for lupus nephritis. A phase 2 trial is ongoing, but Dr. Jackson reported interim analysis of unpublished data that at the one-year mark do show some benefit.

For pediatric lupus nephritis, clinicians still lack FDA-approved treatment options, but the growing options for adult patients provide hope that pediatric options won’t be far behind. As technology, such as single-cell RNA sequencing, advances, Dr. Jackson believes this will help elucidate the pathophysiology of lupus nephritis and provide more targets for future therapies. Questions remain with such agents as voclosporin, belimumab and obinutuzumab, especially in pediatric rheumatology. But this research provides hope for future clinical trials and treatment advances.

Dr. Vogel

Monogenic Lupus

The session’s second speaker was Tiphanie Vogel, MD, PhD, an assistant professor and pediatric rheumatologist at Baylor College of Medicine and Texas Children’s Hospital, Houston. She discussed updates in monogenic lupus.

Dr. Vogel began her presentation discussing three children with a new diagnosis of lupus, highlighting the heterogeneity of the disease. According to Dr. Vogel, genetic and deep-immune profiling tools should allow us to work toward a time when we can meaningfully subgroup our patients in ways that are diagnostically and therapeutically helpful to their care. Although cases of monogenic lupus are rare and contribute only a fraction of the overall heritability, they can significantly inform the pathogenesis and mechanisms of lupus.

Several mechanisms of monogenic lupus have been described and can be grouped into different pathways. Dr. Vogel said these genetic mutations can be related to complement dysregulation, poor apoptotic clearance, poor lymphocyte tolerance and poor nucleic acid sensing leading to enhanced interferon signaling. It’s important to remember these pathways are very interconnected, and it can be helpful to think about how certain disorders may fit into the different groups. This approach is critical to understanding lupus and to the development of better diagnostics and therapeutics.