Janus Kinase Inhibition in the Aicardi–Goutières Syndrome
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The Aicardi–Goutières syndrome is a genetic interferonopathy that is associated with severe disability and death. Most children with this syndrome are unable to walk or talk and have multisystemic complications, including skin inflammation. Janus kinase (JAK) inhibitors may be effective in blocking interferon activation in patients with the Aicardi–Goutières syndrome.

An open-label study of a singlecenter, expanded-access program involving 35 patients with genetically confirmed Aicardi–Goutières syndrome was conducted. The patients received baricitinib, an oral JAK1 and JAK2 inhibitor. JAK inhibitors are associated with infection, anemia, lymphopenia, and thrombosis. Two patients died during the study: one who had been receiving glucocorticoids for a decade, including a 7-year period before the study, had Aicardi– Goutières syndrome–related multisystem organ failure with an opportunistic infection, and the other had Aicardi–Goutières syndrome–related pulmonary hypertension with thrombotic microangiopathy. Among these variables, only thrombocytosis increased in severity during the study.

Patients who are receiving baricitinib should be monitored closely, especially those with underlying thrombotic risk factors or those who are receiving systemic glucocorticoids or immunosuppressive regimens. The measurement of neurologic improvement is complex, but the data suggested improvement in neurologic function, even in patients with severe and long-standing disease.

source: https://www.nejm.org/doi/full/10.1056/NEJMc2001362?rss=searchAndBrowse