JAK Inhibitor Treatment in AGS

Inclusion Criteria

• Clinical or molecular identification of Aicardi Goutières Syndrome including the following features
• Cerebrospinal fluid (CSF) or blood markers suggesting elevations of markers of interferon activation including CSF pleocytosis, elevation of interferon, and/or neopterin and tetrahydrobiopterin elevations
• Evidence of neurologic disease on neuroimaging including intracranial calcifications and or a leukoencephalopathy
• Clinical features of disease including features such as microcephaly, subacute encephalopathy, myopathy, spastic diplegia, skin involvement, autoimmune hepatitis, hematologic abnormalities
• OR have documented mutations felt to be pathogenic in an AGS associated gene.
• Are ≥1 month of age.
• Are ≥4.5 kg in body weight.
• Females after menarche must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
• Parental/guardian permission (informed consent).

Exclusion Criteria

• Are pregnant or nursing at the time of entry or unable to use contraception as detailed below
• Are females of childbearing potential (women >12 or who have had at least one menstrual period regardless of age) who are sexually active and who do not agree to use 2 forms of highly effective methods of birth control (see below) or remain abstinent during the study and for at least 28 days following the last dose of investigational product
• Are sexually active males who do not agree to use 2 forms of highly effective birth control (see below) with female partners of childbearing potential or remain abstinent during the study and for at least 28 days following the last dose of investigational product.
• Each of the following is considered a single highly effective method of birth control (the patient should choose 2):
• oral, injectable, or implanted hormonal contraceptives
• condom with spermicidal foam/gel/film/cream/suppository
• occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
• intrauterine device
• intrauterine system (for example, progestin releasing coil)
• vasectomized male (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)
• Overall health status that in the opinion of the investigator limits the safety of the use of bariticinib
• Have been exposed to a live vaccine within 12 weeks prior to entry or are expected to need/receive a live vaccine (including herpes zoster vaccination) during the course of the study, with the exception of oral rotavirus vaccinations for which the time period is 2 weeks. Young patients who are not yet vaccinated and will be unable to receive live vaccines while they are receiving the program drug (baricitinib) may be included after a documented conversation by a physician not affiliated with the study or the medical monitor with the parents to ensure parental consent and understanding of the risk/benefit ratio of not receiving scheduled vaccinations. These subjects will only be included in the study after a physician obtaining consent also describes the risk/benefit ratio of not receiving scheduled vaccinations.
• Have the following evidence of renal insufficiency:
• An estimated glomerular filtration rate (eGFR) based on the most recent available serum creatinine of 450 msec for males and >470 msec for females); have echocardiogram results that, in the opinion of the investigator, places them at greater risk if included in the study.
• Are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures
• Have received an immunosuppressive biologic agent/monoclonal antibody within 4 half-lives prior to entry, for example, anakinra (4 half- lives=18 hours); etanercept (4 half-lives=18 days); infliximab; or adalimumab (4 half-lives=36 days). Use i