Quantification of Glucocorticoid-Associated Morbidity in Severe Asthma Using the Glucocorticoid Toxicity Index

P. Jane McDowell; John H. Stone; Yuqing Zhang; Kirsty Honeyford; Louise Dunn; R. Jayne Logan; Claire A. Butler; Lorcan P.A. McGarvey; Liam G. Heaney

doi:10.1016/j.jaip.2020.08.032

Quantification of Glucocorticoid-Associated Morbidity in Severe Asthma Using the Glucocorticoid Toxicity Index

P. Jane McDowell, John H. Stone, Yuqing Zhang, Kirsty Honeyford, Louise Dunn, R. Jayne Logan, Claire A. Butler, Lorcan P.A. McGarvey, Liam G. Heaney^*

^*Corresponding author for this work

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

26 Citations (Scopus)

Abstract

Background:

Glucocorticoid (GC)-associated morbidity in severe asthma (SA) is well recognized but varies in individual patients; systematic measurement of GC toxicity is important to measure improvement with steroid-sparing monoclonal antibodies.

Objective: To describe for the first time individual patient GC toxicity in steroid-dependent SA using the Glucocorticoid Toxicity Index (GTI).

Methods: An observational consecutive patient cohort study was performed at a UK Regional SA Specialist clinic for systematic assessment of GC-associated morbidity using the GTI in routine clinical care. GTI was correlated with commonly used patient-reported outcome measures. An approach to GTI scoring, calculation of minimal clinically important difference (MCID), and development of digital GTI application in routine clinical care are described.

Results: All patients had significant oral GC exposure (cumulative prednisolone/prior year, 4280 [3083, 5475] mg) with wide distribution of toxicity in individual patients (mean GTI score, 177.5 [73.7]). GTI score had only modest correlation with recent prednisolone exposure: maintenance prednisolone dose (rho = 0.26, P =.01), cumulative exposure/prior year (rho = 0.38, P <.001), and GC boosts/prior year (rho = 0.25, P =.01). GTI toxicity demonstrated stronger associations with asthma-related quality of life (mini-Asthma Quality of Life Questionnaire [mini-AQLQ] r = −0.50, P <.001 and St. George's Respiratory Questionnaire r = 0.42, P <.001). GTI MCID was calculated as 10 points. Multiple linear regression demonstrated that age and mini-AQLQ were strongest predictors of GC toxicity.

Conclusions: The GTI is a useful tool to systematically capture and quantify GC toxicity at the individual patient level. GC toxicity varies widely between individual patients with SA and correlated only modestly with GC exposure over the preceding year. Age and mini-AQLQ are better predictors of GC toxicity. The GTI and MCID will facilitate assessment of individual SA response to steroid-sparing agents in clinical trials and routine care.

Original language	English
Pages (from-to)	365-372.e5
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	9
Issue number	1
Early online date	01 Sept 2020
DOIs	https://doi.org/10.1016/j.jaip.2020.08.032
Publication status	Published - Jan 2021

Bibliographical note

Funding Information:
Conflicts of interest: P. Jane McDowell has received honoraria from GlaxoSmithKline. J. H. Stone has consulted on glucocorticoid toxicity for Roche/Genentech, ChemoCentryx, Principia Biopharma, Sanofi, Regeneron, InflaRx, and Grunenthal; Copyright of the GTI 2.0 is owned by J.H.Stone’s employers, Massachusetts General Hospital. © 2016, 2018, all rights reserved. K. Honeyford has received honoraria from GlaxoSmithKline, Napp Pharmaceuticals, AstraZeneca, and Teva. C. A. Butler has received honoraria from GlaxoSmithKline, Napp Pharmaceutical, and AstraZeneca. L. P. A. McGarvey has relevant financial activities outside the submitted work including personal fees from Bayer, Merck & Co., Bellus Health, Chiesi, Applied Clinical Intelligence, and Shionogi Inc.; grants from Merck & Co.; and nonfinancial support from Boehringer Ingelheim . L. G. Heaney has received sponsorship for attending international scientific meetings from AstraZeneca , Boehringer Ingelheim , Chiesi , GlaxoSmithKline , and Napp Pharmaceutical ; has received lecture fees/advisory board fees from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia; and has received institutional grant funding from MedImmune , Novartis UK , Roche / Genetech Inc. , and GlaxoSmithKline . In addition, he is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with Amgen, Genetech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine, and Vitalograph. The rest of the authors declare that they have no relevant conflicts of interest.

Funding Information:
Conflicts of interest: P. Jane McDowell has received honoraria from GlaxoSmithKline. J. H. Stone has consulted on glucocorticoid toxicity for Roche/Genentech, ChemoCentryx, Principia Biopharma, Sanofi, Regeneron, InflaRx, and Grunenthal; Copyright of the GTI 2.0 is owned by J.H.Stone's employers, Massachusetts General Hospital. ? 2016, 2018, all rights reserved. K. Honeyford has received honoraria from GlaxoSmithKline, Napp Pharmaceuticals, AstraZeneca, and Teva. C. A. Butler has received honoraria from GlaxoSmithKline, Napp Pharmaceutical, and AstraZeneca. L. P. A. McGarvey has relevant financial activities outside the submitted work including personal fees from Bayer, Merck & Co., Bellus Health, Chiesi, Applied Clinical Intelligence, and Shionogi Inc.; grants from Merck & Co.; and nonfinancial support from Boehringer Ingelheim. L. G. Heaney has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceutical; has received lecture fees/advisory board fees from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia; and has received institutional grant funding from MedImmune, Novartis UK, Roche/Genetech Inc., and GlaxoSmithKline. In addition, he is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with Amgen, Genetech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine, and Vitalograph. The rest of the authors declare that they have no relevant conflicts of interest.

Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

Corticosteroid toxicity
Glucocorticoids
Morbidity
Severe asthma

ASJC Scopus subject areas

Immunology and Allergy

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10.1016/j.jaip.2020.08.032Licence: Unspecified

Exacerbation and glucocorticoid toxicity profile in patients receiving mepolizumab for severe eosinophilic asthma
McDowell, P. J. (Author), Heaney, L. (Supervisor) & McGarvey, L. (Supervisor), Dec 2022
Student thesis: Doctoral Thesis › Doctor of Philosophy

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@article{f7209bdb1b114a5fb7764fd026b6973b,

title = "Quantification of Glucocorticoid-Associated Morbidity in Severe Asthma Using the Glucocorticoid Toxicity Index",

abstract = "Background: Glucocorticoid (GC)-associated morbidity in severe asthma (SA) is well recognized but varies in individual patients; systematic measurement of GC toxicity is important to measure improvement with steroid-sparing monoclonal antibodies. Objective: To describe for the first time individual patient GC toxicity in steroid-dependent SA using the Glucocorticoid Toxicity Index (GTI). Methods: An observational consecutive patient cohort study was performed at a UK Regional SA Specialist clinic for systematic assessment of GC-associated morbidity using the GTI in routine clinical care. GTI was correlated with commonly used patient-reported outcome measures. An approach to GTI scoring, calculation of minimal clinically important difference (MCID), and development of digital GTI application in routine clinical care are described. Results: All patients had significant oral GC exposure (cumulative prednisolone/prior year, 4280 [3083, 5475] mg) with wide distribution of toxicity in individual patients (mean GTI score, 177.5 [73.7]). GTI score had only modest correlation with recent prednisolone exposure: maintenance prednisolone dose (rho = 0.26, P =.01), cumulative exposure/prior year (rho = 0.38, P <.001), and GC boosts/prior year (rho = 0.25, P =.01). GTI toxicity demonstrated stronger associations with asthma-related quality of life (mini-Asthma Quality of Life Questionnaire [mini-AQLQ] r = −0.50, P <.001 and St. George's Respiratory Questionnaire r = 0.42, P <.001). GTI MCID was calculated as 10 points. Multiple linear regression demonstrated that age and mini-AQLQ were strongest predictors of GC toxicity. Conclusions: The GTI is a useful tool to systematically capture and quantify GC toxicity at the individual patient level. GC toxicity varies widely between individual patients with SA and correlated only modestly with GC exposure over the preceding year. Age and mini-AQLQ are better predictors of GC toxicity. The GTI and MCID will facilitate assessment of individual SA response to steroid-sparing agents in clinical trials and routine care.",

keywords = "Corticosteroid toxicity, Glucocorticoids, Morbidity, Severe asthma",

author = "McDowell, {P. Jane} and Stone, {John H.} and Yuqing Zhang and Kirsty Honeyford and Louise Dunn and Logan, {R. Jayne} and Butler, {Claire A.} and McGarvey, {Lorcan P.A.} and Heaney, {Liam G.}",

note = "Funding Information: Conflicts of interest: P. Jane McDowell has received honoraria from GlaxoSmithKline. J. H. Stone has consulted on glucocorticoid toxicity for Roche/Genentech, ChemoCentryx, Principia Biopharma, Sanofi, Regeneron, InflaRx, and Grunenthal; Copyright of the GTI 2.0 is owned by J.H.Stone{\textquoteright}s employers, Massachusetts General Hospital. {\textcopyright} 2016, 2018, all rights reserved. K. Honeyford has received honoraria from GlaxoSmithKline, Napp Pharmaceuticals, AstraZeneca, and Teva. C. A. Butler has received honoraria from GlaxoSmithKline, Napp Pharmaceutical, and AstraZeneca. L. P. A. McGarvey has relevant financial activities outside the submitted work including personal fees from Bayer, Merck & Co., Bellus Health, Chiesi, Applied Clinical Intelligence, and Shionogi Inc.; grants from Merck & Co.; and nonfinancial support from Boehringer Ingelheim . L. G. Heaney has received sponsorship for attending international scientific meetings from AstraZeneca , Boehringer Ingelheim , Chiesi , GlaxoSmithKline , and Napp Pharmaceutical ; has received lecture fees/advisory board fees from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia; and has received institutional grant funding from MedImmune , Novartis UK , Roche / Genetech Inc. , and GlaxoSmithKline . In addition, he is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with Amgen, Genetech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine, and Vitalograph. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Conflicts of interest: P. Jane McDowell has received honoraria from GlaxoSmithKline. J. H. Stone has consulted on glucocorticoid toxicity for Roche/Genentech, ChemoCentryx, Principia Biopharma, Sanofi, Regeneron, InflaRx, and Grunenthal; Copyright of the GTI 2.0 is owned by J.H.Stone's employers, Massachusetts General Hospital. ? 2016, 2018, all rights reserved. K. Honeyford has received honoraria from GlaxoSmithKline, Napp Pharmaceuticals, AstraZeneca, and Teva. C. A. Butler has received honoraria from GlaxoSmithKline, Napp Pharmaceutical, and AstraZeneca. L. P. A. McGarvey has relevant financial activities outside the submitted work including personal fees from Bayer, Merck & Co., Bellus Health, Chiesi, Applied Clinical Intelligence, and Shionogi Inc.; grants from Merck & Co.; and nonfinancial support from Boehringer Ingelheim. L. G. Heaney has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceutical; has received lecture fees/advisory board fees from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia; and has received institutional grant funding from MedImmune, Novartis UK, Roche/Genetech Inc., and GlaxoSmithKline. In addition, he is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with Amgen, Genetech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine, and Vitalograph. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: {\textcopyright} 2020 American Academy of Allergy, Asthma & Immunology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2021",

month = jan,

doi = "10.1016/j.jaip.2020.08.032",

language = "English",

volume = "9",

pages = "365--372.e5",

journal = "Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "Elsevier Inc.",

number = "1",

}

TY - JOUR

T1 - Quantification of Glucocorticoid-Associated Morbidity in Severe Asthma Using the Glucocorticoid Toxicity Index

AU - McDowell, P. Jane

AU - Stone, John H.

AU - Zhang, Yuqing

AU - Honeyford, Kirsty

AU - Dunn, Louise

AU - Logan, R. Jayne

AU - Butler, Claire A.

AU - McGarvey, Lorcan P.A.

AU - Heaney, Liam G.

N1 - Funding Information: Conflicts of interest: P. Jane McDowell has received honoraria from GlaxoSmithKline. J. H. Stone has consulted on glucocorticoid toxicity for Roche/Genentech, ChemoCentryx, Principia Biopharma, Sanofi, Regeneron, InflaRx, and Grunenthal; Copyright of the GTI 2.0 is owned by J.H.Stone’s employers, Massachusetts General Hospital. © 2016, 2018, all rights reserved. K. Honeyford has received honoraria from GlaxoSmithKline, Napp Pharmaceuticals, AstraZeneca, and Teva. C. A. Butler has received honoraria from GlaxoSmithKline, Napp Pharmaceutical, and AstraZeneca. L. P. A. McGarvey has relevant financial activities outside the submitted work including personal fees from Bayer, Merck & Co., Bellus Health, Chiesi, Applied Clinical Intelligence, and Shionogi Inc.; grants from Merck & Co.; and nonfinancial support from Boehringer Ingelheim . L. G. Heaney has received sponsorship for attending international scientific meetings from AstraZeneca , Boehringer Ingelheim , Chiesi , GlaxoSmithKline , and Napp Pharmaceutical ; has received lecture fees/advisory board fees from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia; and has received institutional grant funding from MedImmune , Novartis UK , Roche / Genetech Inc. , and GlaxoSmithKline . In addition, he is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with Amgen, Genetech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine, and Vitalograph. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Conflicts of interest: P. Jane McDowell has received honoraria from GlaxoSmithKline. J. H. Stone has consulted on glucocorticoid toxicity for Roche/Genentech, ChemoCentryx, Principia Biopharma, Sanofi, Regeneron, InflaRx, and Grunenthal; Copyright of the GTI 2.0 is owned by J.H.Stone's employers, Massachusetts General Hospital. ? 2016, 2018, all rights reserved. K. Honeyford has received honoraria from GlaxoSmithKline, Napp Pharmaceuticals, AstraZeneca, and Teva. C. A. Butler has received honoraria from GlaxoSmithKline, Napp Pharmaceutical, and AstraZeneca. L. P. A. McGarvey has relevant financial activities outside the submitted work including personal fees from Bayer, Merck & Co., Bellus Health, Chiesi, Applied Clinical Intelligence, and Shionogi Inc.; grants from Merck & Co.; and nonfinancial support from Boehringer Ingelheim. L. G. Heaney has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceutical; has received lecture fees/advisory board fees from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance, and Circassia; and has received institutional grant funding from MedImmune, Novartis UK, Roche/Genetech Inc., and GlaxoSmithKline. In addition, he is academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with Amgen, Genetech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine, and Vitalograph. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: © 2020 American Academy of Allergy, Asthma & Immunology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - Background: Glucocorticoid (GC)-associated morbidity in severe asthma (SA) is well recognized but varies in individual patients; systematic measurement of GC toxicity is important to measure improvement with steroid-sparing monoclonal antibodies. Objective: To describe for the first time individual patient GC toxicity in steroid-dependent SA using the Glucocorticoid Toxicity Index (GTI). Methods: An observational consecutive patient cohort study was performed at a UK Regional SA Specialist clinic for systematic assessment of GC-associated morbidity using the GTI in routine clinical care. GTI was correlated with commonly used patient-reported outcome measures. An approach to GTI scoring, calculation of minimal clinically important difference (MCID), and development of digital GTI application in routine clinical care are described. Results: All patients had significant oral GC exposure (cumulative prednisolone/prior year, 4280 [3083, 5475] mg) with wide distribution of toxicity in individual patients (mean GTI score, 177.5 [73.7]). GTI score had only modest correlation with recent prednisolone exposure: maintenance prednisolone dose (rho = 0.26, P =.01), cumulative exposure/prior year (rho = 0.38, P <.001), and GC boosts/prior year (rho = 0.25, P =.01). GTI toxicity demonstrated stronger associations with asthma-related quality of life (mini-Asthma Quality of Life Questionnaire [mini-AQLQ] r = −0.50, P <.001 and St. George's Respiratory Questionnaire r = 0.42, P <.001). GTI MCID was calculated as 10 points. Multiple linear regression demonstrated that age and mini-AQLQ were strongest predictors of GC toxicity. Conclusions: The GTI is a useful tool to systematically capture and quantify GC toxicity at the individual patient level. GC toxicity varies widely between individual patients with SA and correlated only modestly with GC exposure over the preceding year. Age and mini-AQLQ are better predictors of GC toxicity. The GTI and MCID will facilitate assessment of individual SA response to steroid-sparing agents in clinical trials and routine care.

AB - Background: Glucocorticoid (GC)-associated morbidity in severe asthma (SA) is well recognized but varies in individual patients; systematic measurement of GC toxicity is important to measure improvement with steroid-sparing monoclonal antibodies. Objective: To describe for the first time individual patient GC toxicity in steroid-dependent SA using the Glucocorticoid Toxicity Index (GTI). Methods: An observational consecutive patient cohort study was performed at a UK Regional SA Specialist clinic for systematic assessment of GC-associated morbidity using the GTI in routine clinical care. GTI was correlated with commonly used patient-reported outcome measures. An approach to GTI scoring, calculation of minimal clinically important difference (MCID), and development of digital GTI application in routine clinical care are described. Results: All patients had significant oral GC exposure (cumulative prednisolone/prior year, 4280 [3083, 5475] mg) with wide distribution of toxicity in individual patients (mean GTI score, 177.5 [73.7]). GTI score had only modest correlation with recent prednisolone exposure: maintenance prednisolone dose (rho = 0.26, P =.01), cumulative exposure/prior year (rho = 0.38, P <.001), and GC boosts/prior year (rho = 0.25, P =.01). GTI toxicity demonstrated stronger associations with asthma-related quality of life (mini-Asthma Quality of Life Questionnaire [mini-AQLQ] r = −0.50, P <.001 and St. George's Respiratory Questionnaire r = 0.42, P <.001). GTI MCID was calculated as 10 points. Multiple linear regression demonstrated that age and mini-AQLQ were strongest predictors of GC toxicity. Conclusions: The GTI is a useful tool to systematically capture and quantify GC toxicity at the individual patient level. GC toxicity varies widely between individual patients with SA and correlated only modestly with GC exposure over the preceding year. Age and mini-AQLQ are better predictors of GC toxicity. The GTI and MCID will facilitate assessment of individual SA response to steroid-sparing agents in clinical trials and routine care.

KW - Corticosteroid toxicity

KW - Glucocorticoids

KW - Morbidity

KW - Severe asthma

U2 - 10.1016/j.jaip.2020.08.032

DO - 10.1016/j.jaip.2020.08.032

M3 - Article

C2 - 32882446

AN - SCOPUS:85091213432

SN - 2213-2198

VL - 9

SP - 365-372.e5

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

IS - 1

ER -

Quantification of Glucocorticoid-Associated Morbidity in Severe Asthma Using the Glucocorticoid Toxicity Index

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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Student theses

Exacerbation and glucocorticoid toxicity profile in patients receiving mepolizumab for severe eosinophilic asthma

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