Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that poses unique diagnostic and therapeutic challenges in children, given they experience more severe disease and higher morbidity than adults. Incomplete disease control and adverse effects limit current treatments. The type I interferon (IFN) signaling axis remains one of the most critical immunologic pathways implicated in SLE and autoinflammatory conditions, such as the rare monogenic disorder called chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). The shared interferon-mediated mechanism provides an immunopathologic bridge and therapeutic target. Anifrolumab, a completely human monoclonal antibody targeting the type I interferon receptor, inhibits the interferon pathway. While the FDA approved anifrolumab for adult patients with moderate to severe SLE, the safety and efficacy have yet to be established in pediatrics. 

Methods: We describe two pediatric patients: one with early-onset, refractory SLE who demonstrated marked clinical improvement while receiving off-label anifrolumab, and another with CANDLE syndrome who exhibited a partial response to baricitinib but achieved significant inflammatory control with the addition of anifrolumab. We also discuss existing anifrolumab literature involving children and its relation to our patients.

Results: Our first patient is a 10-year-old male ultimately diagnosed with monogenic lupus secondary to a C2 deficiency. His disease course has been complex, beginning with macrophage activation syndrome at age 1, inflammatory myositis at age 3, and class II lupus nephritis at age 6, when he was formally diagnosed with SLE. At age 7, he developed significant cutaneous lupus and positive SLE-specific autoantibodies. He was treated with several standard therapies throughout these symptoms, but ultimately experienced control of alopecia, arthralgias, and transaminitis with anifrolumab. Our 11-year-old female was born with multiple comorbidities and required immunosuppressants from a young age due to an orbital pseudotumor. She later developed inflammatory myositis refractory to several therapies. At age seven, genetic testing revealed her previous variant of unknown significance matched a proteasome subunit beta type-8 (PSMB8) mutation that was consistent with CANDLE. Due to the interferonopathy pathophysiology associated with this mutation, anifrolumab was added to her regimen. This allowed for discontinuation of lifelong corticosteroid therapy, leading to marked improvement in muscle weakness, accelerated linear growth, and normalization of cytopenias and muscle enzymes. Both patients showed normalization of interferon signatures and tolerated therapy without significant adverse events.

Conclusion: These cases and existing literature highlight the potential safety and efficacy of interferon blockade in pediatric SLE and autoinflammatory syndromes. Further studies are still needed to establish dosing, safety, and long-term outcomes in the pediatric population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anifrolumab-use-in-youngsters-with-rheumatic-conditions-case-series-and-a-review-of-the-evidence-base/