RT Journal Article
T1 Impact of JAK Inhibitors in Pediatric Patients with STAT1 Gain of Function (GOF) Mutations-10 Children and Review of the Literature.
A1 Deya-Martinez, Angela
A1 Riviere, Jaques G
A1 Roxo-Junior, Persio
A1 Ramakers, Jan
A1 Bloomfield, Marketa
A1 Guisado Hernandez, Paloma
A1 Blanco Lobo, Pilar
A1 Abu Jamra, Soraya Regina
A1 Esteve-Sole, Ana
A1 Kanderova, Veronika
A1 Garcia-Garcia, Ana
A1 Lopez-Corbeto, Mireia
A1 Martinez Pomar, Natalia
A1 Martin-Nalda, Andrea
A1 Alsina, Laia
A1 Neth, Olaf
A1 Olbrich, Peter
K1 Baricitinib
K1 Children
K1 Chronic mucocutaneous candidiasis
K1 Inborn errors of immunity
K1 JAK inhibitors
K1 JAK-STAT pathway
K1 Pediatrics
K1 Primary immunodeficiency disease
K1 Ruxolitinib
K1 STAT1 GOF
AB Since the first description of gain of function (GOF) mutations in signal transducer and activator of transcription (STAT) 1, more than 300 patients have been described with a broad clinical phenotype including infections and severe immune dysregulation. Whilst Jak inhibitors (JAKinibs) have demonstrated benefits in several reported cases, their indications, dosing, and monitoring remain to be established. A retrospective, multicenter study recruiting pediatric patients with STAT1 GOF under JAKinib treatment was performed and, when applicable, compared with the available reports from the literature. Ten children (median age 8.5 years (3-18), receiving JAKinibs (ruxolitinib (n = 9) and baricitinib (n = 1)) with a median follow-up of 18 months (2-42) from 6 inborn errors of immunity (IEI) reference centers were included. Clinical profile and JAKinib indications in our series were similar to the previously published 14 pediatric patients. 9/10 (our cohort) and 14/14 patients (previous reports) showed partial or complete responses. The median immune deficiency and dysregulation activity scores were 15.99 (5.2-40) pre and 7.55 (3-14.1) under therapy (p = 0.0078). Infection, considered a likely adverse event of JAKinib therapy, was observed in 1/10 patients; JAKinibs were stopped in 3/10 children, due to hepatotoxicity, pre-HSCT, and absence of response. Our study supports the potentially beneficial use of JAKinibs in patients with STAT1 GOF, in line with previously published data. However, consensus regarding their indications and timing, dosing, treatment duration, and monitoring, as well as defining biomarkers to monitor clinical and immunological responses, remains to be determined, in form of international prospective multicenter studies using established IEI registries.
PB Springer New York LLC
YR 2022
FD 2022-04-29
LK http://hdl.handle.net/10668/20620
UL http://hdl.handle.net/10668/20620
LA en
NO Deyà-Martínez A, Rivière JG, Roxo-Junior P, Ramakers J, Bloomfield M, Guisado Hernandez P, et al.  Impact of JAK Inhibitors in Pediatric Patients with STAT1 Gain of Function (GOF) Mutations-10 Children and Review of the Literature. J Clin Immunol. 2022 Jul;42(5):1071-1082.
DS RISalud
RD Apr 8, 2025