Short-term efficacy of tofacitinib, a JAK inhibitor, in IFIH1-related Aicardi-Goutières syndrome

Abstract

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous type-I interferonopathy presenting in infancy with intracranial calcifications, white matter lesions, and brain atrophy. AGS7, caused by gain-of-function (GOF) mutations in the IFIH1 gene, triggers excessive type-I interferon production, leading to autoimmune responses. We describe an 18-year-old female diagnosed with AGS7 due to a somatic GOF mutation in IFIH1. In 2014, she presented with multiple joint swelling, facial rash, and hair loss, and received a diagnosis of juvenile idiopathic arthritis and systemic lupus erythematosus. Traditional immunosuppressants were administered, but provided little benefit. Genetic testing in 2023 revealed a GOF variant (p.R720G) in IFIH1. Given the link between IFIH1 variants and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, we administered tofacitinib (a JAK inhibitor) and oral methylprednisolone, with tapering of the traditional immunosuppressants. After nearly one year, the patient showed no significant disease activity and normal hair growth, with no notable changes in thyroid function. Although treatment of AGS remains challenging, this case suggests tofacitinib can successfully manage AGS7 symptoms. More clinical studies are needed to verify the long-term safety and efficacy of tofacitinib.