JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F24%3A10471084" target="_blank" >RIV/00669806:_____/24:10471084 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10471084 RIV/00216208:11130/24:10471084 RIV/00216208:11140/24:10471084 RIV/00064203:_____/24:10471084
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=f074thY9P-" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=f074thY9P-</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jaci.2023.10.018" target="_blank" >10.1016/j.jaci.2023.10.018</a>
Alternative languages
Result language
angličtina
Original language name
JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study
Original language description
BACKGROUND: Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling present with variable manifestations of immune dysregulation and infections. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but initially reported outcomes were poor. JAK inhibitors (JAKi) offer a targeted treatment option that may be an alternative or bridge to HSCT. However, data on their current use, treatment efficacy and adverse events (AE) are limited. OBJECTIVE: We evaluated the current off-label JAKi treatment experience for JAK/STAT IEI among ESID/EBMT-IEWP centers. METHODS: Multicenter retrospective study on patients with a genetic disorder of hyperactive JAK/STAT signaling, who received JAKi treatment for at least 3 months. RESULTS: Sixty-nine patients (72% children) were evaluated (45 STAT1-GOF, 21 STAT3-GOF, 1 STAT5B-GOF, 1 SOCS1-LOF, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, treatment resulted in improvement (partial or complete remission) of clinical symptoms in 87% of STAT1-GOF and in 90% of STAT3-GOF patients. We documented very heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. AE (i.e. infections and weight gain) were frequent (38% of patients), but mild (grade I-II) and transient in most patients. At last follow-up, 52/69 (74%) of patients are still receiving JAKi treatment, while 11 patients eventually underwent HSCT following previous JAKi bridging therapy with a 91% overall survival. CONCLUSIONS: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT-IEI patients. Prospective studies to define optimal JAKi dosing for the variable clinical presentations and age ranges should be pursued.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Allergy and Clinical Immunology
ISSN
0091-6749
e-ISSN
1097-6825
Volume of the periodical
153
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
275-286
UT code for WoS article
001159754000001
EID of the result in the Scopus database
2-s2.0-85178371751