Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

Sarah C. Grünert; Terry G. J. Derks; Katarina Adrian; Khalid Al-Thihli; Diana Ballhausen; Joanna Bidiuk; Andrea Bordugo; Monica Boyer; Drago Bratkovic; Michaela Brunner-Krainz; Alberto Burlina; Anupam Chakrapani; Willemijn Corpeleijn; Alison Cozens; Charlotte Dawson; Helena Dhamko; Maja Djordjevic Milosevic; Hernan Eiroa; Yael Finezilber; Carolina Fischinger Moura de Souza; Maria Concepción Garcia-Jiménez; Serena Gasperini; Dorothea Haas; Johannes Häberle; Rebecca Halligan; Law Hiu Fung; Alexandra Hörbe-Blindt; Laura Maria Horka; Martina Huemer; Sema Kalkan Uçar; Bozica Kecman; Sebile Kilavuz; Gergely Kriván; Martin Lindner; Natalia Lüsebrink; Konstantinos Makrilkakis; Anne Mei-Kwun Kwok; Esther M. Maier; Arianna Maiorana; Shawn E. McCandless; John James Mitchell; Hiroshi Mizumoto; Helen Mundy; Carlos Ochoa; Kathryn Pierce; Pilar Quijada Fraile; Debra Regier; Alessandro Rossi; René Santer; Hester C. Schuman; Piotr Sobieraj; Johannes Spenger; Ronen Spiegel; Karolina M. Stepien; Galit Tal; Mojca Zerjav Tanšek; Ana Drole Torkar; Michel Tchan; Santhosh Thyagu; Samantha A. Schrier Vergano; Erika Vucko; Natalie Weinhold; Petra Zsidegh; Saskia B. Wortmann

doi:10.1016/j.gim.2022.04.001

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

Sarah C. Grünert^*, Terry G. J. Derks, Katarina Adrian, Khalid Al-Thihli, Diana Ballhausen, Joanna Bidiuk, Andrea Bordugo, Monica Boyer, Drago Bratkovic, Michaela Brunner-Krainz, Alberto Burlina, Anupam Chakrapani, Willemijn Corpeleijn, Alison Cozens, Charlotte Dawson, Helena Dhamko, Maja Djordjevic Milosevic, Hernan Eiroa, Yael Finezilber, Carolina Fischinger Moura de SouzaMaria Concepción Garcia-Jiménez, Serena Gasperini, Dorothea Haas, Johannes Häberle, Rebecca Halligan, Law Hiu Fung, Alexandra Hörbe-Blindt, Laura Maria Horka, Martina Huemer, Sema Kalkan Uçar, Bozica Kecman, Sebile Kilavuz, Gergely Kriván, Martin Lindner, Natalia Lüsebrink, Konstantinos Makrilkakis, Anne Mei-Kwun Kwok, Esther M. Maier, Arianna Maiorana, Shawn E. McCandless, John James Mitchell, Hiroshi Mizumoto, Helen Mundy, Carlos Ochoa, Kathryn Pierce, Pilar Quijada Fraile, Debra Regier, Alessandro Rossi, René Santer, Hester C. Schuman, Piotr Sobieraj, Johannes Spenger, Ronen Spiegel, Karolina M. Stepien, Galit Tal, Mojca Zerjav Tanšek, Ana Drole Torkar, Michel Tchan, Santhosh Thyagu, Samantha A. Schrier Vergano, Erika Vucko, Natalie Weinhold, Petra Zsidegh, Saskia B. Wortmann

^*Corresponding author for this work

Pediatric surgery

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction–related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction–related symptoms and safety profile in individuals with GSD Ib.

Original language	English
Pages (from-to)	1781-1788
Number of pages	8
Journal	Genetics in Medicine
Volume	24
Issue number	8
Early online date	2022
DOIs	https://doi.org/10.1016/j.gim.2022.04.001
Publication status	Published - Aug 2022

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10.1016/j.gim.2022.04.001

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Grünert, S. C., Derks, T. G. J., Adrian, K., Al-Thihli, K., Ballhausen, D., Bidiuk, J., Bordugo, A., Boyer, M., Bratkovic, D., Brunner-Krainz, M., Burlina, A., Chakrapani, A., Corpeleijn, W., Cozens, A., Dawson, C., Dhamko, H., Milosevic, M. D., Eiroa, H., Finezilber, Y., ... Wortmann, S. B. (2022). Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire. Genetics in Medicine, 24(8), 1781-1788. https://doi.org/10.1016/j.gim.2022.04.001

@article{a9396a00aa66442a8a88ca4a4b6aae61,

title = "Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire",

abstract = "Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction–related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction–related symptoms and safety profile in individuals with GSD Ib.",

keywords = "GSD Ib, Glycogen storage disease type Ib, Neutropenia, SGLT2 inhibitors, SLC37A4",

author = "Gr{\"u}nert, {Sarah C.} and Derks, {Terry G. J.} and Katarina Adrian and Khalid Al-Thihli and Diana Ballhausen and Joanna Bidiuk and Andrea Bordugo and Monica Boyer and Drago Bratkovic and Michaela Brunner-Krainz and Alberto Burlina and Anupam Chakrapani and Willemijn Corpeleijn and Alison Cozens and Charlotte Dawson and Helena Dhamko and Milosevic, {Maja Djordjevic} and Hernan Eiroa and Yael Finezilber and {Moura de Souza}, {Carolina Fischinger} and Garcia-Jim{\'e}nez, {Maria Concepci{\'o}n} and Serena Gasperini and Dorothea Haas and Johannes H{\"a}berle and Rebecca Halligan and Fung, {Law Hiu} and Alexandra H{\"o}rbe-Blindt and Horka, {Laura Maria} and Martina Huemer and U{\c c}ar, {Sema Kalkan} and Bozica Kecman and Sebile Kilavuz and Gergely Kriv{\'a}n and Martin Lindner and Natalia L{\"u}sebrink and Konstantinos Makrilkakis and {Mei-Kwun Kwok}, Anne and Maier, {Esther M.} and Arianna Maiorana and McCandless, {Shawn E.} and Mitchell, {John James} and Hiroshi Mizumoto and Helen Mundy and Carlos Ochoa and Kathryn Pierce and Fraile, {Pilar Quijada} and Debra Regier and Alessandro Rossi and Ren{\'e} Santer and Schuman, {Hester C.} and Piotr Sobieraj and Johannes Spenger and Ronen Spiegel and Stepien, {Karolina M.} and Galit Tal and Tan{\v s}ek, {Mojca Zerjav} and Torkar, {Ana Drole} and Michel Tchan and Santhosh Thyagu and {Schrier Vergano}, {Samantha A.} and Erika Vucko and Natalie Weinhold and Petra Zsidegh and Wortmann, {Saskia B.}",

note = "Funding Information: Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (Project ID No. 739543). We are grateful to Hanka Dekker and Caroline van Essen (representing Volwassen Kinderen en Stofwisselingsziekten, the Dutch metabolic patient organization) and Enrique Contreras (representing Asociacion Espa{\~n}ola de Enfermos de Glucogenosis, the Spanish glycogen storage disease patient organization) for co-creation of the webinars and their input during the development of the questionnaire. This research has been supported by Nina Contreras D'Agosto, a little girl living with Glycogen Storage Disease type 1b, and her parents Marta D'Agosto and Enrique Landelino Contreras “Lande”, through the platform “Nina The Warrior” and its thousands of followers and donors at www.ninalaguerrera.org. They are members of the Board of Directors of the Global GSD1b Research Alliance “CureGSD1b” (www.curegsd1b.org), a growing world-wide community with nearly 200 GSD1b patients and families. Conceptualization: S.C.G. T.G.J.D. S.B.W.; Data Curation: all authors; Formal Analysis: S.C.G. T.G.J.D. S.B.W.; Methodology: S.C.G. T.G.J.D. S.B.W.; Project Administration: S.C.G. T.G.J.D. S.B.W.; Software: T.G.J.D.; Supervision: S.C.G. T.G.J.D. S.B.W.; Writing-original draft: S.C.G. T.G.J.D. S.B.W.; Writing-review and editing: S.C.G. T.G.J.D. K.A. K.A.T. D.B. J.B. A.B. M.B. D.B. M.B.K. A.B. A.C. W.C. A.C. C.D. H.D. M.D.M. H.E. Y.F. C.F.D.S. Ma.C.G.J. S.G. D.H. J.H. R.H. L.H.F. A.H.B. L.M.H. M.H. S.K.U. B.K. S.K. G.K. M.L. N.L. K.M. A.M.K.K, E.M.M. A.M. S.E.M. J.J.M. H.M. H.M. C.O. K.P. P.Q.F. D.R. A.R. R.S. H.C.S. P.S. J.S. R.S. K.M.S. G.T. M.Z.T. A.D.T. M.T. S.T. S.A.S.V. E.V. N.W. P.Z. S.B.W. This is a retrospective collection of anonymized data collected during regular patient care, for which, in line with the Declaration of Helsinki,12 neither individual patients{\textquoteright} consent nor formal research ethics committee approval was required. Authors at institutions that required patient consent were responsible to obtain this permission from the patient or guardian. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = aug,

doi = "10.1016/j.gim.2022.04.001",

language = "English",

volume = "24",

pages = "1781--1788",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Lippincott Williams and Wilkins",

number = "8",

}

Grünert, SC, Derks, TGJ, Adrian, K, Al-Thihli, K, Ballhausen, D, Bidiuk, J, Bordugo, A, Boyer, M, Bratkovic, D, Brunner-Krainz, M, Burlina, A, Chakrapani, A, Corpeleijn, W, Cozens, A, Dawson, C, Dhamko, H, Milosevic, MD, Eiroa, H, Finezilber, Y, Moura de Souza, CF, Garcia-Jiménez, MC, Gasperini, S, Haas, D, Häberle, J, Halligan, R, Fung, LH, Hörbe-Blindt, A, Horka, LM, Huemer, M, Uçar, SK, Kecman, B, Kilavuz, S, Kriván, G, Lindner, M, Lüsebrink, N, Makrilkakis, K, Mei-Kwun Kwok, A, Maier, EM, Maiorana, A, McCandless, SE, Mitchell, JJ, Mizumoto, H, Mundy, H, Ochoa, C, Pierce, K, Fraile, PQ, Regier, D, Rossi, A, Santer, R, Schuman, HC, Sobieraj, P, Spenger, J, Spiegel, R, Stepien, KM, Tal, G, Tanšek, MZ, Torkar, AD, Tchan, M, Thyagu, S, Schrier Vergano, SA, Vucko, E, Weinhold, N, Zsidegh, P & Wortmann, SB 2022, 'Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire', Genetics in Medicine, vol. 24, no. 8, pp. 1781-1788. https://doi.org/10.1016/j.gim.2022.04.001

TY - JOUR

T1 - Efficacy and safety of empagliflozin in glycogen storage disease type Ib

T2 - Data from an international questionnaire

AU - Grünert, Sarah C.

AU - Derks, Terry G. J.

AU - Adrian, Katarina

AU - Al-Thihli, Khalid

AU - Ballhausen, Diana

AU - Bidiuk, Joanna

AU - Bordugo, Andrea

AU - Boyer, Monica

AU - Bratkovic, Drago

AU - Brunner-Krainz, Michaela

AU - Burlina, Alberto

AU - Chakrapani, Anupam

AU - Corpeleijn, Willemijn

AU - Cozens, Alison

AU - Dawson, Charlotte

AU - Dhamko, Helena

AU - Milosevic, Maja Djordjevic

AU - Eiroa, Hernan

AU - Finezilber, Yael

AU - Moura de Souza, Carolina Fischinger

AU - Garcia-Jiménez, Maria Concepción

AU - Gasperini, Serena

AU - Haas, Dorothea

AU - Häberle, Johannes

AU - Halligan, Rebecca

AU - Fung, Law Hiu

AU - Hörbe-Blindt, Alexandra

AU - Horka, Laura Maria

AU - Huemer, Martina

AU - Uçar, Sema Kalkan

AU - Kecman, Bozica

AU - Kilavuz, Sebile

AU - Kriván, Gergely

AU - Lindner, Martin

AU - Lüsebrink, Natalia

AU - Makrilkakis, Konstantinos

AU - Mei-Kwun Kwok, Anne

AU - Maier, Esther M.

AU - Maiorana, Arianna

AU - McCandless, Shawn E.

AU - Mitchell, John James

AU - Mizumoto, Hiroshi

AU - Mundy, Helen

AU - Ochoa, Carlos

AU - Pierce, Kathryn

AU - Fraile, Pilar Quijada

AU - Regier, Debra

AU - Rossi, Alessandro

AU - Santer, René

AU - Schuman, Hester C.

AU - Sobieraj, Piotr

AU - Spenger, Johannes

AU - Spiegel, Ronen

AU - Stepien, Karolina M.

AU - Tal, Galit

AU - Tanšek, Mojca Zerjav

AU - Torkar, Ana Drole

AU - Tchan, Michel

AU - Thyagu, Santhosh

AU - Schrier Vergano, Samantha A.

AU - Vucko, Erika

AU - Weinhold, Natalie

AU - Zsidegh, Petra

AU - Wortmann, Saskia B.

N1 - Funding Information: Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (Project ID No. 739543). We are grateful to Hanka Dekker and Caroline van Essen (representing Volwassen Kinderen en Stofwisselingsziekten, the Dutch metabolic patient organization) and Enrique Contreras (representing Asociacion Española de Enfermos de Glucogenosis, the Spanish glycogen storage disease patient organization) for co-creation of the webinars and their input during the development of the questionnaire. This research has been supported by Nina Contreras D'Agosto, a little girl living with Glycogen Storage Disease type 1b, and her parents Marta D'Agosto and Enrique Landelino Contreras “Lande”, through the platform “Nina The Warrior” and its thousands of followers and donors at www.ninalaguerrera.org. They are members of the Board of Directors of the Global GSD1b Research Alliance “CureGSD1b” (www.curegsd1b.org), a growing world-wide community with nearly 200 GSD1b patients and families. Conceptualization: S.C.G. T.G.J.D. S.B.W.; Data Curation: all authors; Formal Analysis: S.C.G. T.G.J.D. S.B.W.; Methodology: S.C.G. T.G.J.D. S.B.W.; Project Administration: S.C.G. T.G.J.D. S.B.W.; Software: T.G.J.D.; Supervision: S.C.G. T.G.J.D. S.B.W.; Writing-original draft: S.C.G. T.G.J.D. S.B.W.; Writing-review and editing: S.C.G. T.G.J.D. K.A. K.A.T. D.B. J.B. A.B. M.B. D.B. M.B.K. A.B. A.C. W.C. A.C. C.D. H.D. M.D.M. H.E. Y.F. C.F.D.S. Ma.C.G.J. S.G. D.H. J.H. R.H. L.H.F. A.H.B. L.M.H. M.H. S.K.U. B.K. S.K. G.K. M.L. N.L. K.M. A.M.K.K, E.M.M. A.M. S.E.M. J.J.M. H.M. H.M. C.O. K.P. P.Q.F. D.R. A.R. R.S. H.C.S. P.S. J.S. R.S. K.M.S. G.T. M.Z.T. A.D.T. M.T. S.T. S.A.S.V. E.V. N.W. P.Z. S.B.W. This is a retrospective collection of anonymized data collected during regular patient care, for which, in line with the Declaration of Helsinki,12 neither individual patients’ consent nor formal research ethics committee approval was required. Authors at institutions that required patient consent were responsible to obtain this permission from the patient or guardian. Publisher Copyright: © 2022 The Authors

PY - 2022/8

Y1 - 2022/8

N2 - Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction–related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction–related symptoms and safety profile in individuals with GSD Ib.

AB - Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction–related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction–related symptoms and safety profile in individuals with GSD Ib.

KW - GSD Ib

KW - Glycogen storage disease type Ib

KW - Neutropenia

KW - SGLT2 inhibitors

KW - SLC37A4

UR - http://www.scopus.com/inward/record.url?scp=85129682988&partnerID=8YFLogxK

U2 - 10.1016/j.gim.2022.04.001

DO - 10.1016/j.gim.2022.04.001

M3 - Article

C2 - 35503103

SN - 1098-3600

VL - 24

SP - 1781

EP - 1788

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 8

ER -

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

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