JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study
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...
Ausführliche Beschreibung
Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
Enthalten in: The journal of allergy and clinical immunology - Amsterdam [u.a.] : Elsevier, 1971, 153, Seite 275-286.e18 |
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Übergeordnetes Werk: |
volume:153 ; pages:275-286.e18 |
DOI / URN: |
10.1016/j.jaci.2023.10.018 |
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Katalog-ID: |
ELV066425913 |
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035 | |a (DE-627)ELV066425913 | ||
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041 | |a eng | ||
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084 | |a 44.78 |2 bkl | ||
100 | 1 | |a Fischer, Marco |e verfasserin |0 (orcid)0000-0002-2704-7912 |4 aut | |
245 | 1 | 0 | |a JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study |
264 | 1 | |c 2023 | |
336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a 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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. | ||
650 | 4 | |a JAK/STAT signaling | |
650 | 4 | |a gain of function | |
650 | 4 | |a immune dysregulation | |
650 | 4 | |a primary immunodeficiency | |
650 | 4 | |a inborn error of immunity | |
650 | 4 | |a JAK inhibitor | |
650 | 4 | |a autoimmunity | |
650 | 4 | |a ruxolitinib | |
650 | 4 | |a baricitinib | |
650 | 4 | |a chronic mucocutaneous candidiasis | |
700 | 1 | |a Olbrich, Peter |e verfasserin |4 aut | |
700 | 1 | |a Hadjadj, Jérôme |e verfasserin |4 aut | |
700 | 1 | |a Aumann, Volker |e verfasserin |4 aut | |
700 | 1 | |a Bakhtiar, Shahrzad |e verfasserin |4 aut | |
700 | 1 | |a Barlogis, Vincent |e verfasserin |4 aut | |
700 | 1 | |a von Bismarck, Philipp |e verfasserin |4 aut | |
700 | 1 | |a Bloomfield, Markéta |e verfasserin |4 aut | |
700 | 1 | |a Booth, Claire |e verfasserin |4 aut | |
700 | 1 | |a Buddingh, Emmeline P. |e verfasserin |4 aut | |
700 | 1 | |a Cagdas, Deniz |e verfasserin |4 aut | |
700 | 1 | |a Castelle, Martin |e verfasserin |4 aut | |
700 | 1 | |a Chan, Alice Y. |e verfasserin |4 aut | |
700 | 1 | |a Chandrakasan, Shanmuganathan |e verfasserin |4 aut | |
700 | 1 | |a Chetty, Kritika |e verfasserin |4 aut | |
700 | 1 | |a Cougoul, Pierre |e verfasserin |4 aut | |
700 | 1 | |a Crickx, Etienne |e verfasserin |4 aut | |
700 | 1 | |a Dara, Jasmeen |e verfasserin |4 aut | |
700 | 1 | |a Deyà-Martínez, Angela |e verfasserin |4 aut | |
700 | 1 | |a Farmand, Susan |e verfasserin |4 aut | |
700 | 1 | |a Formankova, Renata |e verfasserin |4 aut | |
700 | 1 | |a Gennery, Andrew R. |e verfasserin |4 aut | |
700 | 1 | |a Gonzalez-Granado, Luis Ignacio |e verfasserin |4 aut | |
700 | 1 | |a Hagin, David |e verfasserin |4 aut | |
700 | 1 | |a Hanitsch, Leif Gunnar |e verfasserin |4 aut | |
700 | 1 | |a Hanzlikovà, Jana |e verfasserin |4 aut | |
700 | 1 | |a Hauck, Fabian |e verfasserin |4 aut | |
700 | 1 | |a Ivorra-Cortés, José |e verfasserin |4 aut | |
700 | 1 | |a Kisand, Kai |e verfasserin |4 aut | |
700 | 1 | |a Kiykim, Ayca |e verfasserin |4 aut | |
700 | 1 | |a Körholz, Julia |e verfasserin |4 aut | |
700 | 1 | |a Leahy, Timothy Ronan |e verfasserin |4 aut | |
700 | 1 | |a van Montfrans, Joris |e verfasserin |4 aut | |
700 | 1 | |a Nademi, Zohreh |e verfasserin |4 aut | |
700 | 1 | |a Nelken, Brigitte |e verfasserin |4 aut | |
700 | 1 | |a Parikh, Suhag |e verfasserin |4 aut | |
700 | 1 | |a Plado, Silvi |e verfasserin |4 aut | |
700 | 1 | |a Ramakers, Jan |e verfasserin |4 aut | |
700 | 1 | |a Redlich, Antje |e verfasserin |4 aut | |
700 | 1 | |a Rieux-Laucat, Frédéric |e verfasserin |4 aut | |
700 | 1 | |a Rivière, Jacques G. |e verfasserin |4 aut | |
700 | 1 | |a Rodina, Yulia |e verfasserin |4 aut | |
700 | 1 | |a Júnior, Pérsio Roxo |e verfasserin |4 aut | |
700 | 1 | |a Salou, Sarah |e verfasserin |4 aut | |
700 | 1 | |a Schuetz, Catharina |e verfasserin |4 aut | |
700 | 1 | |a Shcherbina, Anna |e verfasserin |4 aut | |
700 | 1 | |a Slatter, Mary A. |e verfasserin |4 aut | |
700 | 1 | |a Touzot, Fabien |e verfasserin |4 aut | |
700 | 1 | |a Unal, Ekrem |e verfasserin |4 aut | |
700 | 1 | |a Lankester, Arjan C. |e verfasserin |4 aut | |
700 | 1 | |a Burns, Siobhan |e verfasserin |4 aut | |
700 | 1 | |a Seppänen, Mikko R.J. |e verfasserin |4 aut | |
700 | 1 | |a Neth, Olaf |e verfasserin |4 aut | |
700 | 1 | |a Albert, Michael H. |e verfasserin |4 aut | |
700 | 1 | |a Ehl, Stephan |e verfasserin |4 aut | |
700 | 1 | |a Neven, Bénédicte |e verfasserin |4 aut | |
700 | 1 | |a Speckmann, Carsten |e verfasserin |0 (orcid)0000-0002-6217-1556 |4 aut | |
773 | 0 | 8 | |i Enthalten in |t The journal of allergy and clinical immunology |d Amsterdam [u.a.] : Elsevier, 1971 |g 153, Seite 275-286.e18 |h Online-Ressource |w (DE-627)32045553X |w (DE-600)2006613-2 |w (DE-576)094478864 |x 1097-6825 |7 nnns |
773 | 1 | 8 | |g volume:153 |g pages:275-286.e18 |
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912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_31 | ||
912 | |a GBV_ILN_32 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
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912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_90 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_100 | ||
912 | |a GBV_ILN_101 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_168 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_187 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_224 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_370 | ||
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912 | |a GBV_ILN_702 | ||
912 | |a GBV_ILN_2001 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2004 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2007 | ||
912 | |a GBV_ILN_2008 | ||
912 | |a GBV_ILN_2009 | ||
912 | |a GBV_ILN_2010 | ||
912 | |a GBV_ILN_2011 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_2015 | ||
912 | |a GBV_ILN_2020 | ||
912 | |a GBV_ILN_2021 | ||
912 | |a GBV_ILN_2025 | ||
912 | |a GBV_ILN_2026 | ||
912 | |a GBV_ILN_2027 | ||
912 | |a GBV_ILN_2034 | ||
912 | |a GBV_ILN_2044 | ||
912 | |a GBV_ILN_2048 | ||
912 | |a GBV_ILN_2049 | ||
912 | |a GBV_ILN_2050 | ||
912 | |a GBV_ILN_2055 | ||
912 | |a GBV_ILN_2056 | ||
912 | |a GBV_ILN_2059 | ||
912 | |a GBV_ILN_2061 | ||
912 | |a GBV_ILN_2064 | ||
912 | |a GBV_ILN_2088 | ||
912 | |a GBV_ILN_2106 | ||
912 | |a GBV_ILN_2110 | ||
912 | |a GBV_ILN_2111 | ||
912 | |a GBV_ILN_2112 | ||
912 | |a GBV_ILN_2122 | ||
912 | |a GBV_ILN_2129 | ||
912 | |a GBV_ILN_2143 | ||
912 | |a GBV_ILN_2152 | ||
912 | |a GBV_ILN_2153 | ||
912 | |a GBV_ILN_2190 | ||
912 | |a GBV_ILN_2232 | ||
912 | |a GBV_ILN_2336 | ||
912 | |a GBV_ILN_2470 | ||
912 | |a GBV_ILN_2507 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4035 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4242 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4251 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4326 | ||
912 | |a GBV_ILN_4333 | ||
912 | |a GBV_ILN_4334 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4393 | ||
912 | |a GBV_ILN_4700 | ||
936 | b | k | |a 44.45 |j Immunologie |q VZ |
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10.1016/j.jaci.2023.10.018 doi (DE-627)ELV066425913 (ELSEVIER)S0091-6749(23)01390-8 DE-627 ger DE-627 rda eng 610 VZ 44.45 bkl 44.78 bkl Fischer, Marco verfasserin (orcid)0000-0002-2704-7912 aut JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis Olbrich, Peter verfasserin aut Hadjadj, Jérôme verfasserin aut Aumann, Volker verfasserin aut Bakhtiar, Shahrzad verfasserin aut Barlogis, Vincent verfasserin aut von Bismarck, Philipp verfasserin aut Bloomfield, Markéta verfasserin aut Booth, Claire verfasserin aut Buddingh, Emmeline P. verfasserin aut Cagdas, Deniz verfasserin aut Castelle, Martin verfasserin aut Chan, Alice Y. verfasserin aut Chandrakasan, Shanmuganathan verfasserin aut Chetty, Kritika verfasserin aut Cougoul, Pierre verfasserin aut Crickx, Etienne verfasserin aut Dara, Jasmeen verfasserin aut Deyà-Martínez, Angela verfasserin aut Farmand, Susan verfasserin aut Formankova, Renata verfasserin aut Gennery, Andrew R. verfasserin aut Gonzalez-Granado, Luis Ignacio verfasserin aut Hagin, David verfasserin aut Hanitsch, Leif Gunnar verfasserin aut Hanzlikovà, Jana verfasserin aut Hauck, Fabian verfasserin aut Ivorra-Cortés, José verfasserin aut Kisand, Kai verfasserin aut Kiykim, Ayca verfasserin aut Körholz, Julia verfasserin aut Leahy, Timothy Ronan verfasserin aut van Montfrans, Joris verfasserin aut Nademi, Zohreh verfasserin aut Nelken, Brigitte verfasserin aut Parikh, Suhag verfasserin aut Plado, Silvi verfasserin aut Ramakers, Jan verfasserin aut Redlich, Antje verfasserin aut Rieux-Laucat, Frédéric verfasserin aut Rivière, Jacques G. verfasserin aut Rodina, Yulia verfasserin aut Júnior, Pérsio Roxo verfasserin aut Salou, Sarah verfasserin aut Schuetz, Catharina verfasserin aut Shcherbina, Anna verfasserin aut Slatter, Mary A. verfasserin aut Touzot, Fabien verfasserin aut Unal, Ekrem verfasserin aut Lankester, Arjan C. verfasserin aut Burns, Siobhan verfasserin aut Seppänen, Mikko R.J. verfasserin aut Neth, Olaf verfasserin aut Albert, Michael H. verfasserin aut Ehl, Stephan verfasserin aut Neven, Bénédicte verfasserin aut Speckmann, Carsten verfasserin (orcid)0000-0002-6217-1556 aut Enthalten in The journal of allergy and clinical immunology Amsterdam [u.a.] : Elsevier, 1971 153, Seite 275-286.e18 Online-Ressource (DE-627)32045553X (DE-600)2006613-2 (DE-576)094478864 1097-6825 nnns volume:153 pages:275-286.e18 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 44.45 Immunologie VZ 44.78 Immunkrankheiten VZ AR 153 275-286.e18 |
spelling |
10.1016/j.jaci.2023.10.018 doi (DE-627)ELV066425913 (ELSEVIER)S0091-6749(23)01390-8 DE-627 ger DE-627 rda eng 610 VZ 44.45 bkl 44.78 bkl Fischer, Marco verfasserin (orcid)0000-0002-2704-7912 aut JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis Olbrich, Peter verfasserin aut Hadjadj, Jérôme verfasserin aut Aumann, Volker verfasserin aut Bakhtiar, Shahrzad verfasserin aut Barlogis, Vincent verfasserin aut von Bismarck, Philipp verfasserin aut Bloomfield, Markéta verfasserin aut Booth, Claire verfasserin aut Buddingh, Emmeline P. verfasserin aut Cagdas, Deniz verfasserin aut Castelle, Martin verfasserin aut Chan, Alice Y. verfasserin aut Chandrakasan, Shanmuganathan verfasserin aut Chetty, Kritika verfasserin aut Cougoul, Pierre verfasserin aut Crickx, Etienne verfasserin aut Dara, Jasmeen verfasserin aut Deyà-Martínez, Angela verfasserin aut Farmand, Susan verfasserin aut Formankova, Renata verfasserin aut Gennery, Andrew R. verfasserin aut Gonzalez-Granado, Luis Ignacio verfasserin aut Hagin, David verfasserin aut Hanitsch, Leif Gunnar verfasserin aut Hanzlikovà, Jana verfasserin aut Hauck, Fabian verfasserin aut Ivorra-Cortés, José verfasserin aut Kisand, Kai verfasserin aut Kiykim, Ayca verfasserin aut Körholz, Julia verfasserin aut Leahy, Timothy Ronan verfasserin aut van Montfrans, Joris verfasserin aut Nademi, Zohreh verfasserin aut Nelken, Brigitte verfasserin aut Parikh, Suhag verfasserin aut Plado, Silvi verfasserin aut Ramakers, Jan verfasserin aut Redlich, Antje verfasserin aut Rieux-Laucat, Frédéric verfasserin aut Rivière, Jacques G. verfasserin aut Rodina, Yulia verfasserin aut Júnior, Pérsio Roxo verfasserin aut Salou, Sarah verfasserin aut Schuetz, Catharina verfasserin aut Shcherbina, Anna verfasserin aut Slatter, Mary A. verfasserin aut Touzot, Fabien verfasserin aut Unal, Ekrem verfasserin aut Lankester, Arjan C. verfasserin aut Burns, Siobhan verfasserin aut Seppänen, Mikko R.J. verfasserin aut Neth, Olaf verfasserin aut Albert, Michael H. verfasserin aut Ehl, Stephan verfasserin aut Neven, Bénédicte verfasserin aut Speckmann, Carsten verfasserin (orcid)0000-0002-6217-1556 aut Enthalten in The journal of allergy and clinical immunology Amsterdam [u.a.] : Elsevier, 1971 153, Seite 275-286.e18 Online-Ressource (DE-627)32045553X (DE-600)2006613-2 (DE-576)094478864 1097-6825 nnns volume:153 pages:275-286.e18 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 44.45 Immunologie VZ 44.78 Immunkrankheiten VZ AR 153 275-286.e18 |
allfields_unstemmed |
10.1016/j.jaci.2023.10.018 doi (DE-627)ELV066425913 (ELSEVIER)S0091-6749(23)01390-8 DE-627 ger DE-627 rda eng 610 VZ 44.45 bkl 44.78 bkl Fischer, Marco verfasserin (orcid)0000-0002-2704-7912 aut JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis Olbrich, Peter verfasserin aut Hadjadj, Jérôme verfasserin aut Aumann, Volker verfasserin aut Bakhtiar, Shahrzad verfasserin aut Barlogis, Vincent verfasserin aut von Bismarck, Philipp verfasserin aut Bloomfield, Markéta verfasserin aut Booth, Claire verfasserin aut Buddingh, Emmeline P. verfasserin aut Cagdas, Deniz verfasserin aut Castelle, Martin verfasserin aut Chan, Alice Y. verfasserin aut Chandrakasan, Shanmuganathan verfasserin aut Chetty, Kritika verfasserin aut Cougoul, Pierre verfasserin aut Crickx, Etienne verfasserin aut Dara, Jasmeen verfasserin aut Deyà-Martínez, Angela verfasserin aut Farmand, Susan verfasserin aut Formankova, Renata verfasserin aut Gennery, Andrew R. verfasserin aut Gonzalez-Granado, Luis Ignacio verfasserin aut Hagin, David verfasserin aut Hanitsch, Leif Gunnar verfasserin aut Hanzlikovà, Jana verfasserin aut Hauck, Fabian verfasserin aut Ivorra-Cortés, José verfasserin aut Kisand, Kai verfasserin aut Kiykim, Ayca verfasserin aut Körholz, Julia verfasserin aut Leahy, Timothy Ronan verfasserin aut van Montfrans, Joris verfasserin aut Nademi, Zohreh verfasserin aut Nelken, Brigitte verfasserin aut Parikh, Suhag verfasserin aut Plado, Silvi verfasserin aut Ramakers, Jan verfasserin aut Redlich, Antje verfasserin aut Rieux-Laucat, Frédéric verfasserin aut Rivière, Jacques G. verfasserin aut Rodina, Yulia verfasserin aut Júnior, Pérsio Roxo verfasserin aut Salou, Sarah verfasserin aut Schuetz, Catharina verfasserin aut Shcherbina, Anna verfasserin aut Slatter, Mary A. verfasserin aut Touzot, Fabien verfasserin aut Unal, Ekrem verfasserin aut Lankester, Arjan C. verfasserin aut Burns, Siobhan verfasserin aut Seppänen, Mikko R.J. verfasserin aut Neth, Olaf verfasserin aut Albert, Michael H. verfasserin aut Ehl, Stephan verfasserin aut Neven, Bénédicte verfasserin aut Speckmann, Carsten verfasserin (orcid)0000-0002-6217-1556 aut Enthalten in The journal of allergy and clinical immunology Amsterdam [u.a.] : Elsevier, 1971 153, Seite 275-286.e18 Online-Ressource (DE-627)32045553X (DE-600)2006613-2 (DE-576)094478864 1097-6825 nnns volume:153 pages:275-286.e18 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 44.45 Immunologie VZ 44.78 Immunkrankheiten VZ AR 153 275-286.e18 |
allfieldsGer |
10.1016/j.jaci.2023.10.018 doi (DE-627)ELV066425913 (ELSEVIER)S0091-6749(23)01390-8 DE-627 ger DE-627 rda eng 610 VZ 44.45 bkl 44.78 bkl Fischer, Marco verfasserin (orcid)0000-0002-2704-7912 aut JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis Olbrich, Peter verfasserin aut Hadjadj, Jérôme verfasserin aut Aumann, Volker verfasserin aut Bakhtiar, Shahrzad verfasserin aut Barlogis, Vincent verfasserin aut von Bismarck, Philipp verfasserin aut Bloomfield, Markéta verfasserin aut Booth, Claire verfasserin aut Buddingh, Emmeline P. verfasserin aut Cagdas, Deniz verfasserin aut Castelle, Martin verfasserin aut Chan, Alice Y. verfasserin aut Chandrakasan, Shanmuganathan verfasserin aut Chetty, Kritika verfasserin aut Cougoul, Pierre verfasserin aut Crickx, Etienne verfasserin aut Dara, Jasmeen verfasserin aut Deyà-Martínez, Angela verfasserin aut Farmand, Susan verfasserin aut Formankova, Renata verfasserin aut Gennery, Andrew R. verfasserin aut Gonzalez-Granado, Luis Ignacio verfasserin aut Hagin, David verfasserin aut Hanitsch, Leif Gunnar verfasserin aut Hanzlikovà, Jana verfasserin aut Hauck, Fabian verfasserin aut Ivorra-Cortés, José verfasserin aut Kisand, Kai verfasserin aut Kiykim, Ayca verfasserin aut Körholz, Julia verfasserin aut Leahy, Timothy Ronan verfasserin aut van Montfrans, Joris verfasserin aut Nademi, Zohreh verfasserin aut Nelken, Brigitte verfasserin aut Parikh, Suhag verfasserin aut Plado, Silvi verfasserin aut Ramakers, Jan verfasserin aut Redlich, Antje verfasserin aut Rieux-Laucat, Frédéric verfasserin aut Rivière, Jacques G. verfasserin aut Rodina, Yulia verfasserin aut Júnior, Pérsio Roxo verfasserin aut Salou, Sarah verfasserin aut Schuetz, Catharina verfasserin aut Shcherbina, Anna verfasserin aut Slatter, Mary A. verfasserin aut Touzot, Fabien verfasserin aut Unal, Ekrem verfasserin aut Lankester, Arjan C. verfasserin aut Burns, Siobhan verfasserin aut Seppänen, Mikko R.J. verfasserin aut Neth, Olaf verfasserin aut Albert, Michael H. verfasserin aut Ehl, Stephan verfasserin aut Neven, Bénédicte verfasserin aut Speckmann, Carsten verfasserin (orcid)0000-0002-6217-1556 aut Enthalten in The journal of allergy and clinical immunology Amsterdam [u.a.] : Elsevier, 1971 153, Seite 275-286.e18 Online-Ressource (DE-627)32045553X (DE-600)2006613-2 (DE-576)094478864 1097-6825 nnns volume:153 pages:275-286.e18 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 44.45 Immunologie VZ 44.78 Immunkrankheiten VZ AR 153 275-286.e18 |
allfieldsSound |
10.1016/j.jaci.2023.10.018 doi (DE-627)ELV066425913 (ELSEVIER)S0091-6749(23)01390-8 DE-627 ger DE-627 rda eng 610 VZ 44.45 bkl 44.78 bkl Fischer, Marco verfasserin (orcid)0000-0002-2704-7912 aut JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis Olbrich, Peter verfasserin aut Hadjadj, Jérôme verfasserin aut Aumann, Volker verfasserin aut Bakhtiar, Shahrzad verfasserin aut Barlogis, Vincent verfasserin aut von Bismarck, Philipp verfasserin aut Bloomfield, Markéta verfasserin aut Booth, Claire verfasserin aut Buddingh, Emmeline P. verfasserin aut Cagdas, Deniz verfasserin aut Castelle, Martin verfasserin aut Chan, Alice Y. verfasserin aut Chandrakasan, Shanmuganathan verfasserin aut Chetty, Kritika verfasserin aut Cougoul, Pierre verfasserin aut Crickx, Etienne verfasserin aut Dara, Jasmeen verfasserin aut Deyà-Martínez, Angela verfasserin aut Farmand, Susan verfasserin aut Formankova, Renata verfasserin aut Gennery, Andrew R. verfasserin aut Gonzalez-Granado, Luis Ignacio verfasserin aut Hagin, David verfasserin aut Hanitsch, Leif Gunnar verfasserin aut Hanzlikovà, Jana verfasserin aut Hauck, Fabian verfasserin aut Ivorra-Cortés, José verfasserin aut Kisand, Kai verfasserin aut Kiykim, Ayca verfasserin aut Körholz, Julia verfasserin aut Leahy, Timothy Ronan verfasserin aut van Montfrans, Joris verfasserin aut Nademi, Zohreh verfasserin aut Nelken, Brigitte verfasserin aut Parikh, Suhag verfasserin aut Plado, Silvi verfasserin aut Ramakers, Jan verfasserin aut Redlich, Antje verfasserin aut Rieux-Laucat, Frédéric verfasserin aut Rivière, Jacques G. verfasserin aut Rodina, Yulia verfasserin aut Júnior, Pérsio Roxo verfasserin aut Salou, Sarah verfasserin aut Schuetz, Catharina verfasserin aut Shcherbina, Anna verfasserin aut Slatter, Mary A. verfasserin aut Touzot, Fabien verfasserin aut Unal, Ekrem verfasserin aut Lankester, Arjan C. verfasserin aut Burns, Siobhan verfasserin aut Seppänen, Mikko R.J. verfasserin aut Neth, Olaf verfasserin aut Albert, Michael H. verfasserin aut Ehl, Stephan verfasserin aut Neven, Bénédicte verfasserin aut Speckmann, Carsten verfasserin (orcid)0000-0002-6217-1556 aut Enthalten in The journal of allergy and clinical immunology Amsterdam [u.a.] : Elsevier, 1971 153, Seite 275-286.e18 Online-Ressource (DE-627)32045553X (DE-600)2006613-2 (DE-576)094478864 1097-6825 nnns volume:153 pages:275-286.e18 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 44.45 Immunologie VZ 44.78 Immunkrankheiten VZ AR 153 275-286.e18 |
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Enthalten in The journal of allergy and clinical immunology 153, Seite 275-286.e18 volume:153 pages:275-286.e18 |
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Enthalten in The journal of allergy and clinical immunology 153, Seite 275-286.e18 volume:153 pages:275-286.e18 |
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JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis |
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Fischer, Marco @@aut@@ Olbrich, Peter @@aut@@ Hadjadj, Jérôme @@aut@@ Aumann, Volker @@aut@@ Bakhtiar, Shahrzad @@aut@@ Barlogis, Vincent @@aut@@ von Bismarck, Philipp @@aut@@ Bloomfield, Markéta @@aut@@ Booth, Claire @@aut@@ Buddingh, Emmeline P. @@aut@@ Cagdas, Deniz @@aut@@ Castelle, Martin @@aut@@ Chan, Alice Y. @@aut@@ Chandrakasan, Shanmuganathan @@aut@@ Chetty, Kritika @@aut@@ Cougoul, Pierre @@aut@@ Crickx, Etienne @@aut@@ Dara, Jasmeen @@aut@@ Deyà-Martínez, Angela @@aut@@ Farmand, Susan @@aut@@ Formankova, Renata @@aut@@ Gennery, Andrew R. @@aut@@ Gonzalez-Granado, Luis Ignacio @@aut@@ Hagin, David @@aut@@ Hanitsch, Leif Gunnar @@aut@@ Hanzlikovà, Jana @@aut@@ Hauck, Fabian @@aut@@ Ivorra-Cortés, José @@aut@@ Kisand, Kai @@aut@@ Kiykim, Ayca @@aut@@ Körholz, Julia @@aut@@ Leahy, Timothy Ronan @@aut@@ van Montfrans, Joris @@aut@@ Nademi, Zohreh @@aut@@ Nelken, Brigitte @@aut@@ Parikh, Suhag @@aut@@ Plado, Silvi @@aut@@ Ramakers, Jan @@aut@@ Redlich, Antje @@aut@@ Rieux-Laucat, Frédéric @@aut@@ Rivière, Jacques G. @@aut@@ Rodina, Yulia @@aut@@ Júnior, Pérsio Roxo @@aut@@ Salou, Sarah @@aut@@ Schuetz, Catharina @@aut@@ Shcherbina, Anna @@aut@@ Slatter, Mary A. @@aut@@ Touzot, Fabien @@aut@@ Unal, Ekrem @@aut@@ Lankester, Arjan C. @@aut@@ Burns, Siobhan @@aut@@ Seppänen, Mikko R.J. @@aut@@ Neth, Olaf @@aut@@ Albert, Michael H. @@aut@@ Ehl, Stephan @@aut@@ Neven, Bénédicte @@aut@@ Speckmann, Carsten @@aut@@ |
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2023-01-01T00:00:00Z |
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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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 91% overall survival.Conclusions: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT IEI patients. 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Fischer, Marco |
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610 VZ 44.45 bkl 44.78 bkl JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study JAK/STAT signaling gain of function immune dysregulation primary immunodeficiency inborn error of immunity JAK inhibitor autoimmunity ruxolitinib baricitinib chronic mucocutaneous candidiasis |
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JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study |
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Fischer, Marco Olbrich, Peter Hadjadj, Jérôme Aumann, Volker Bakhtiar, Shahrzad Barlogis, Vincent von Bismarck, Philipp Bloomfield, Markéta Booth, Claire Buddingh, Emmeline P. Cagdas, Deniz Castelle, Martin Chan, Alice Y. Chandrakasan, Shanmuganathan Chetty, Kritika Cougoul, Pierre Crickx, Etienne Dara, Jasmeen Deyà-Martínez, Angela Farmand, Susan Formankova, Renata Gennery, Andrew R. Gonzalez-Granado, Luis Ignacio Hagin, David Hanitsch, Leif Gunnar Hanzlikovà, Jana Hauck, Fabian Ivorra-Cortés, José Kisand, Kai Kiykim, Ayca Körholz, Julia Leahy, Timothy Ronan van Montfrans, Joris Nademi, Zohreh Nelken, Brigitte Parikh, Suhag Plado, Silvi Ramakers, Jan Redlich, Antje Rieux-Laucat, Frédéric Rivière, Jacques G. Rodina, Yulia Júnior, Pérsio Roxo Salou, Sarah Schuetz, Catharina Shcherbina, Anna Slatter, Mary A. Touzot, Fabien Unal, Ekrem Lankester, Arjan C. Burns, Siobhan Seppänen, Mikko R.J. Neth, Olaf Albert, Michael H. Ehl, Stephan Neven, Bénédicte Speckmann, Carsten |
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jak inhibitor treatment for inborn errors of jak/stat signaling: an esid/ebmt-iewp retrospective study |
title_auth |
JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study |
abstract |
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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. |
abstractGer |
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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. |
abstract_unstemmed |
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 are limited.Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers.Methods: We conducted a 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 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 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 highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 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. |
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title_short |
JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study |
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Olbrich, Peter Hadjadj, Jérôme Aumann, Volker Bakhtiar, Shahrzad Barlogis, Vincent von Bismarck, Philipp Bloomfield, Markéta Booth, Claire Buddingh, Emmeline P. Cagdas, Deniz Castelle, Martin Chan, Alice Y. Chandrakasan, Shanmuganathan Chetty, Kritika Cougoul, Pierre Crickx, Etienne Dara, Jasmeen Deyà-Martínez, Angela Farmand, Susan Formankova, Renata Gennery, Andrew R. Gonzalez-Granado, Luis Ignacio Hagin, David Hanitsch, Leif Gunnar Hanzlikovà, Jana Hauck, Fabian Ivorra-Cortés, José Kisand, Kai Kiykim, Ayca Körholz, Julia Leahy, Timothy Ronan van Montfrans, Joris Nademi, Zohreh Nelken, Brigitte Parikh, Suhag Plado, Silvi Ramakers, Jan Redlich, Antje Rieux-Laucat, Frédéric Rivière, Jacques G. Rodina, Yulia Júnior, Pérsio Roxo Salou, Sarah Schuetz, Catharina Shcherbina, Anna Slatter, Mary A. Touzot, Fabien Unal, Ekrem Lankester, Arjan C. Burns, Siobhan Seppänen, Mikko R.J. Neth, Olaf Albert, Michael H. Ehl, Stephan Neven, Bénédicte Speckmann, Carsten |
author2Str |
Olbrich, Peter Hadjadj, Jérôme Aumann, Volker Bakhtiar, Shahrzad Barlogis, Vincent von Bismarck, Philipp Bloomfield, Markéta Booth, Claire Buddingh, Emmeline P. Cagdas, Deniz Castelle, Martin Chan, Alice Y. Chandrakasan, Shanmuganathan Chetty, Kritika Cougoul, Pierre Crickx, Etienne Dara, Jasmeen Deyà-Martínez, Angela Farmand, Susan Formankova, Renata Gennery, Andrew R. Gonzalez-Granado, Luis Ignacio Hagin, David Hanitsch, Leif Gunnar Hanzlikovà, Jana Hauck, Fabian Ivorra-Cortés, José Kisand, Kai Kiykim, Ayca Körholz, Julia Leahy, Timothy Ronan van Montfrans, Joris Nademi, Zohreh Nelken, Brigitte Parikh, Suhag Plado, Silvi Ramakers, Jan Redlich, Antje Rieux-Laucat, Frédéric Rivière, Jacques G. Rodina, Yulia Júnior, Pérsio Roxo Salou, Sarah Schuetz, Catharina Shcherbina, Anna Slatter, Mary A. Touzot, Fabien Unal, Ekrem Lankester, Arjan C. Burns, Siobhan Seppänen, Mikko R.J. Neth, Olaf Albert, Michael H. Ehl, Stephan Neven, Bénédicte Speckmann, Carsten |
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doi_str |
10.1016/j.jaci.2023.10.018 |
up_date |
2024-07-06T17:43:02.716Z |
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