Anifrolumab use in children with refractory rheumatic conditions and elevated interferon signatures: A case report.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease where loss of immune tolerance and pathogenic autoantibody production lead to multisystem inflammation and damage. The type I interferon (IFN-I) signaling axis remains a critical immunologic pathway implicated in SLE and autoinflammatory conditions, such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). The shared IFN-mediated mechanism may provide a shared therapeutic target between diseases. Anifrolumab, a fully human monoclonal antibody targeting the IFN-I receptor, is FDA-approved for adult patients with moderate to severe SLE, but its safety and efficacy are not well established in pediatric patients. The current literature supporting the use of anifrolumab in pediatric rheumatologic conditions is limited to case reports and small case series describing anifrolumab use in refractory dermatologic manifestations of SLE and dermatomyositis and type 1 interferonopathies, such as CANDLE and STING-associated vasculopathy with onset in infancy (SAVI). We add to this literature by describing 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. These cases described how our patients benefited systemically from IFN blockade in refractory pediatric SLE and CANDLE syndrome. Further clinical trials are still needed to establish dosing, safety, and long-term outcomes in pediatric populations, given case series and reports are limited by lack of standardization, blinding, and sample size.