Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma

Ekaterina Khaleva; Chris Brightling; Thomas Eiwegger; Alan Altraja; Philippe Bégin; Katharina Blumchen; Apostolos Bossios; Arnaud Bourdin; Anneke Ten Brinke; Guy Brusselle; Roxana Silvia Bumbacea; Andrew Bush; Thomas B. Casale; Graham W. Clarke; Rekha Chaudhuri; Kian Fan Chung; Courtney Coleman; Jonathan Corren; Sven Erik Dahlén; Antoine Deschildre; Ratko Djukanovic; Katrien Eger; Andrew Exley; Louise Fleming; David J. Jackson; Ji Hyang Lee; Clare S. Murray; Katharine C. Pike; Steve Turner; Graham Roberts; behalf of the 3TR Asthma Definition of Response Working Group

doi:10.1183/13993003.00691-2024

Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma

Ekaterina Khaleva
, Chris Brightling
, Thomas Eiwegger
, Alan Altraja
, Philippe Bégin
, Katharina Blumchen
, Apostolos Bossios
, Arnaud Bourdin
, Anneke Ten Brinke
, Guy Brusselle
, Roxana Silvia Bumbacea
, Andrew Bush
, Thomas B. Casale
, Graham W. Clarke
, Rekha Chaudhuri
, Kian Fan Chung
, Courtney Coleman
, Jonathan Corren
, Sven Erik Dahlén
, Antoine Deschildre

Ratko Djukanovic, Katrien Eger, Andrew Exley, Louise Fleming, David J. Jackson, Ji Hyang Lee, Clare S. Murray, Katharine C. Pike, Steve Turner, Graham Roberts^*, behalf of the 3TR Asthma Definition of Response Working Group

^*Corresponding author for this work

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

18 Citations (Scopus)

Abstract

Background
We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biological therapies for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life.

Methods
International expert healthcare professionals and patients with severe asthma were invited to 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA, 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of healthcare professionals evaluated CONFiRM's external validity.

Results
Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroid use were rated as the most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between healthcare professionals and patients, although patients assigned greater importance to quality of life. The CONFiRM score quantified response to a biologic from −31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (area under the curve ≥0.92) and a substantial (area under the curve ≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult, respectively; p<0.0001).

Conclusions
We have developed novel patient-centred paediatric and adult CONFiRMs that include quality of life measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.

Original language	English
Article number	2400691
Number of pages	19
Journal	European Respiratory Journal
Volume	65
Issue number	3
Early online date	27 Mar 2025
DOIs	https://doi.org/10.1183/13993003.00691-2024
Publication status	E-pub ahead of print - 27 Mar 2025

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Publisher Copyright:
Copyright ©The authors 2025.

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Khaleva, E., Brightling, C., Eiwegger, T., Altraja, A., Bégin, P., Blumchen, K., Bossios, A., Bourdin, A., Brinke, A. T., Brusselle, G., Bumbacea, R. S., Bush, A., Casale, T. B., Clarke, G. W., Chaudhuri, R., Chung, K. F., Coleman, C., Corren, J., Dahlén, S. E., ... behalf of the 3TR Asthma Definition of Response Working Group (2025). Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma. European Respiratory Journal, 65(3), Article 2400691. Advance online publication. https://doi.org/10.1183/13993003.00691-2024

@article{ecb83721cd2e4da3af33c6ccbb3091b4,

title = "Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma",

abstract = "Background We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biological therapies for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life. Methods International expert healthcare professionals and patients with severe asthma were invited to 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA, 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of healthcare professionals evaluated CONFiRM's external validity. Results Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroid use were rated as the most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between healthcare professionals and patients, although patients assigned greater importance to quality of life. The CONFiRM score quantified response to a biologic from −31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (area under the curve ≥0.92) and a substantial (area under the curve ≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult, respectively; p<0.0001). Conclusions We have developed novel patient-centred paediatric and adult CONFiRMs that include quality of life measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.",

author = "Ekaterina Khaleva and Chris Brightling and Thomas Eiwegger and Alan Altraja and Philippe B{\'e}gin and Katharina Blumchen and Apostolos Bossios and Arnaud Bourdin and Brinke, \{Anneke Ten\} and Guy Brusselle and Bumbacea, \{Roxana Silvia\} and Andrew Bush and Casale, \{Thomas B.\} and Clarke, \{Graham W.\} and Rekha Chaudhuri and Chung, \{Kian Fan\} and Courtney Coleman and Jonathan Corren and Dahl{\'e}n, \{Sven Erik\} and Antoine Deschildre and Ratko Djukanovic and Katrien Eger and Andrew Exley and Louise Fleming and Jackson, \{David J.\} and Lee, \{Ji Hyang\} and Murray, \{Clare S.\} and Pike, \{Katharine C.\} and Steve Turner and Graham Roberts and \{behalf of the 3TR Asthma Definition of Response Working Group\}",

note = "Publisher Copyright: Copyright {\textcopyright}The authors 2025.",

year = "2025",

month = mar,

day = "27",

doi = "10.1183/13993003.00691-2024",

language = "English",

volume = "65",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "3",

}

Khaleva, E, Brightling, C, Eiwegger, T, Altraja, A, Bégin, P, Blumchen, K, Bossios, A, Bourdin, A, Brinke, AT, Brusselle, G, Bumbacea, RS, Bush, A, Casale, TB, Clarke, GW, Chaudhuri, R, Chung, KF, Coleman, C, Corren, J, Dahlén, SE, Deschildre, A, Djukanovic, R, Eger, K, Exley, A, Fleming, L, Jackson, DJ, Lee, JH, Murray, CS, Pike, KC, Turner, S, Roberts, G & behalf of the 3TR Asthma Definition of Response Working Group 2025, 'Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma', European Respiratory Journal, vol. 65, no. 3, 2400691. https://doi.org/10.1183/13993003.00691-2024

TY - JOUR

T1 - Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma

AU - Khaleva, Ekaterina

AU - Brightling, Chris

AU - Eiwegger, Thomas

AU - Altraja, Alan

AU - Bégin, Philippe

AU - Blumchen, Katharina

AU - Bossios, Apostolos

AU - Bourdin, Arnaud

AU - Brinke, Anneke Ten

AU - Brusselle, Guy

AU - Bumbacea, Roxana Silvia

AU - Bush, Andrew

AU - Casale, Thomas B.

AU - Clarke, Graham W.

AU - Chaudhuri, Rekha

AU - Chung, Kian Fan

AU - Coleman, Courtney

AU - Corren, Jonathan

AU - Dahlén, Sven Erik

AU - Deschildre, Antoine

AU - Djukanovic, Ratko

AU - Eger, Katrien

AU - Exley, Andrew

AU - Fleming, Louise

AU - Jackson, David J.

AU - Lee, Ji Hyang

AU - Murray, Clare S.

AU - Pike, Katharine C.

AU - Turner, Steve

AU - Roberts, Graham

AU - behalf of the 3TR Asthma Definition of Response Working Group

PY - 2025/3/27

Y1 - 2025/3/27

N2 - Background We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biological therapies for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life. Methods International expert healthcare professionals and patients with severe asthma were invited to 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA, 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of healthcare professionals evaluated CONFiRM's external validity. Results Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroid use were rated as the most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between healthcare professionals and patients, although patients assigned greater importance to quality of life. The CONFiRM score quantified response to a biologic from −31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (area under the curve ≥0.92) and a substantial (area under the curve ≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult, respectively; p<0.0001). Conclusions We have developed novel patient-centred paediatric and adult CONFiRMs that include quality of life measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.

AB - Background We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biological therapies for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life. Methods International expert healthcare professionals and patients with severe asthma were invited to 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA, 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of healthcare professionals evaluated CONFiRM's external validity. Results Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroid use were rated as the most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between healthcare professionals and patients, although patients assigned greater importance to quality of life. The CONFiRM score quantified response to a biologic from −31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (area under the curve ≥0.92) and a substantial (area under the curve ≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult, respectively; p<0.0001). Conclusions We have developed novel patient-centred paediatric and adult CONFiRMs that include quality of life measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.

UR - https://www.scopus.com/pages/publications/105004022308

U2 - 10.1183/13993003.00691-2024

DO - 10.1183/13993003.00691-2024

M3 - Article (Academic Journal)

C2 - 39510551

AN - SCOPUS:105004022308

SN - 0903-1936

VL - 65

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 3

M1 - 2400691

ER -

Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma

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