Baricitinib in Two Pediatric Patients with COPA syndrome: A Case Series and Literature Review

Abstract

COPA syndrome is a rare, autosomal dominant inborn error of immunity driven by dysregulated type I interferon signaling. It typically presents in early childhood with interstitial lung disease (ILD), arthritis, and systemic inflammation. Current treatments are largely extrapolated from adult protocols, and disease management remains challenging. Recent evidence suggests that Janus kinase inhibitors (JAKi), which block interferon signaling, may offer a targeted therapeutic approach. We report two pediatric patients with genetically confirmed COPA syndrome who demonstrated sustained clinical improvement following initiation of baricitinib, a JAKi. Both cases exhibited early-onset ILD and systemic inflammation. Genetic testing identified pathogenic variants in the COPA gene. Conventional immunosuppressants provided only partial and temporary relief with disease flares when immunosuppression was tapered. Baricitinib was initiated, and both patients showed rapid clinical response, improved pulmonary function, reduced systemic inflammation, lung parenchymal radiographic stabilization, and improvement of ILD symptoms. Baricitinib was well tolerated overall and enabled tapering and discontinuation of corticosteroids and other immunosuppressants. These cases align with limited existing literature showing efficacy of JAKi in COPA syndrome and further support the role of precision medicine targeting type I interferonopathies. While long-term safety data remain limited, early findings suggest that JAK inhibition represents a promising therapeutic strategy in COPA syndrome. Careful monitoring for viral reactivation and infection is essential. Larger studies and longer follow-up are needed to validate these results and to optimize management of this complex pediatric autoimmune disease.