Article ; Online: JAK Inhibition in Aicardi-Goutières Syndrome: a Monocentric Multidisciplinary Real-World Approach Study.
Journal of clinical immunology
2023 Volume 43, Issue 6, Page(s) 1436–1447
Abstract: The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a ... ...
| Abstract | The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery. |
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| MeSH term(s) | Humans ; Autoimmune Diseases of the Nervous System/diagnosis ; Autoimmune Diseases of the Nervous System/drug therapy ; Autoimmune Diseases of the Nervous System/genetics ; Nervous System Malformations/diagnosis ; Nervous System Malformations/drug therapy ; Nervous System Malformations/genetics ; Signal Transduction ; Genetic Testing | |||||
| Language | English | |||||
| Publishing date | 2023-05-12 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 779361-3 | |||||
| ISSN | 1573-2592 ; 0271-9142 | |||||
| ISSN (online) | 1573-2592 | |||||
| ISSN | 0271-9142 | |||||
| DOI | 10.1007/s10875-023-01500-z | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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