JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10471084 RIV/00216208:11130/24:10471084 RIV/00216208:11140/24:10471084 RIV/00064203:_____/24:10471084

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Allergy and Clinical Immunology

ISSN

0091-6749

e-ISSN

1097-6825

Svazek periodika

153

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

275-286

Kód UT WoS článku

001159754000001

EID výsledku v databázi Scopus

2-s2.0-85178371751