Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome.

Details

Serval ID
serval:BIB_399FE048032A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome.
Journal
Journal of clinical immunology
Author(s)
Volpi S., Insalaco A., Caorsi R., Santori E., Messia V., Sacco O., Terheggen-Lagro S., Cardinale F., Scarselli A., Pastorino C., Moneta G., Cangemi G., Passarelli C., Ricci M., Girosi D., Derchi M., Bocca P., Diociaiuti A., El Hachem M., Cancrini C., Tomà P., Granata C., Ravelli A., Candotti F., Picco P., DeBenedetti F., Gattorno M.
ISSN
1573-2592 (Electronic)
ISSN-L
0271-9142
Publication state
Published
Issued date
07/2019
Peer-reviewed
Oui
Volume
39
Number
5
Pages
476-485
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib.
We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis.
We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease.
We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.
Keywords
Child, Child, Preschool, Female, Humans, Interferon Type I/blood, Janus Kinase Inhibitors/adverse effects, Janus Kinase Inhibitors/therapeutic use, Lung Diseases, Interstitial/blood, Lung Diseases, Interstitial/drug therapy, Lung Diseases, Interstitial/genetics, Membrane Proteins/genetics, Off-Label Use, Pyrazoles/adverse effects, Pyrazoles/therapeutic use, Receptor, Interferon alpha-beta/antagonists & inhibitors, Skin Diseases/blood, Skin Diseases/drug therapy, Skin Diseases/genetics, Syndrome, Treatment Outcome, Vascular Diseases/blood, Vascular Diseases/drug therapy, Vascular Diseases/genetics, JAK inhibitor, Recurrent fever, pulmonary fibrosis
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2019 0:14
Last modification date
07/07/2020 5:20
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