Exploring definitions and predictors of response to biologics for severe asthma

Ghislaine Scelo; Trung N Tran; Tham T Le; Malin Faregås; Delbert Dorscheid; John Busby; Mona Al-Ahmad; Riyad Al-Lehebi; Alan Altraja; Aaron Beastall; Celine Bergeron; Leif Bjermer; Anne S Bjerrum; Diana Jimena Cano-Rosales; Giorgio Walter Canonica; Victoria Carter; Jeremy Charriot; George C Christoff; Borja G Cosio; Eve Denton; Maria Jose Fernandez-Sanchez; João A Fonseca; Peter G Gibson; Celine Goh; Liam G Heaney; Enrico Heffler; Mark Hew; Takashi Iwanaga; Rohit Katial; Mariko S Koh; Piotr Kuna; Désirée Larenas-Linnemann; Lauri Lehtimäki; Bassam Mahboub; Neil Martin; Hisako Matsumoto; Andrew N Menzies-Gow; Nikolaos G Papadopoulos; Pujan Patel; Luis Perez-De-Llano; Matthew Peters; Paul E Pfeffer; Todor A Popov; Celeste M Porsbjerg; Chin K Rhee; Mohsen Sadatsafavi; Camille Taillé; Carlos A Torres-Duque; Ming-Ju Tsai; Charlotte S Ulrik; John W Upham; Anna von Bülow; Eileen Wang; Michael E Wechsler; David B Price

doi:10.1016/j.jaip.2024.05.016

Exploring definitions and predictors of response to biologics for severe asthma

Ghislaine Scelo, Trung N Tran, Tham T Le, Malin Faregås, Delbert Dorscheid, John Busby, Mona Al-Ahmad, Riyad Al-Lehebi, Alan Altraja, Aaron Beastall, Celine Bergeron, Leif Bjermer, Anne S Bjerrum, Diana Jimena Cano-Rosales, Giorgio Walter Canonica, Victoria Carter, Jeremy Charriot, George C Christoff, Borja G Cosio, Eve DentonMaria Jose Fernandez-Sanchez, João A Fonseca, Peter G Gibson, Celine Goh, Liam G Heaney, Enrico Heffler, Mark Hew, Takashi Iwanaga, Rohit Katial, Mariko S Koh, Piotr Kuna, Désirée Larenas-Linnemann, Lauri Lehtimäki, Bassam Mahboub, Neil Martin, Hisako Matsumoto, Andrew N Menzies-Gow, Nikolaos G Papadopoulos, Pujan Patel, Luis Perez-De-Llano, Matthew Peters, Paul E Pfeffer, Todor A Popov, Celeste M Porsbjerg, Chin K Rhee, Mohsen Sadatsafavi, Camille Taillé, Carlos A Torres-Duque, Ming-Ju Tsai, Charlotte S Ulrik, John W Upham, Anna von Bülow, Eileen Wang, Michael E Wechsler, David B Price

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Abstract

BACKGROUND: Biologic effectiveness is often assessed as 'response', a term which eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.

OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.

METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in 4 asthma outcome domains were assessed in the 1-year period pre- and post-biologic-initiation in patients with predefined level of pre-biologic impairment. Responder cut-offs were: ≥50% reduction in exacerbation rate, ≥50% reduction in long-term oral corticosteroid [LTOCS] daily dose, ≥1 category improvement in asthma control, and ≥100mL improvement in FEV1. Responders were defined using single- and multiple-domains. The association between pre-biologic characteristics and post-biologic-initiation response were examined by multivariable analysis.

RESULTS: 2,210 patients were included. Responder rate ranged from 80.7% (n=566/701) for exacerbation-response to 10.6% (n=9/85) for 4-domain-response. Many responders still exhibited significant impairment post-biologic-initiation: 46.7% (n=206/441) of asthma control-responders with uncontrolled asthma pre-biologic still had incompletely-controlled disease post-biologic-initiation. Predictors of response were outcome-dependent. Lung function-responders were more likely to have higher pre-biologic FeNO (OR:1.20 for every 25ppb increase), and shorter asthma duration (OR:0.81, for every 10-year increase in duration). Higher BEC and presence of T2-related comorbidities were positively associated with higher odds of meeting LTOCS-, control- and lung function-responder criteria.

CONCLUSION: Our findings underscore the multi-modal nature of 'response', show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed.

Original language	English
Pages (from-to)	2347-2361
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	12
Issue number	9
Early online date	18 May 2024
DOIs	https://doi.org/10.1016/j.jaip.2024.05.016
Publication status	Published - 05 Sept 2024

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Exploring definitions and predictors of response to biologics for severe asthma
Copyright 2024 the authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 610 KBLicence: CC BY-NC-ND

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Scelo, G., Tran, T. N., Le, T. T., Faregås, M., Dorscheid, D., Busby, J., Al-Ahmad, M., Al-Lehebi, R., Altraja, A., Beastall, A., Bergeron, C., Bjermer, L., Bjerrum, A. S., Cano-Rosales, D. J., Canonica, G. W., Carter, V., Charriot, J., Christoff, G. C., Cosio, B. G., ... Price, D. B. (2024). Exploring definitions and predictors of response to biologics for severe asthma. Journal of Allergy and Clinical Immunology: In Practice, 12(9), 2347-2361. https://doi.org/10.1016/j.jaip.2024.05.016

@article{c579368280894a0ca61986d6cbcc1f0b,

title = "Exploring definitions and predictors of response to biologics for severe asthma",

abstract = "BACKGROUND: Biologic effectiveness is often assessed as 'response', a term which eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in 4 asthma outcome domains were assessed in the 1-year period pre- and post-biologic-initiation in patients with predefined level of pre-biologic impairment. Responder cut-offs were: ≥50% reduction in exacerbation rate, ≥50% reduction in long-term oral corticosteroid [LTOCS] daily dose, ≥1 category improvement in asthma control, and ≥100mL improvement in FEV1. Responders were defined using single- and multiple-domains. The association between pre-biologic characteristics and post-biologic-initiation response were examined by multivariable analysis.RESULTS: 2,210 patients were included. Responder rate ranged from 80.7% (n=566/701) for exacerbation-response to 10.6% (n=9/85) for 4-domain-response. Many responders still exhibited significant impairment post-biologic-initiation: 46.7% (n=206/441) of asthma control-responders with uncontrolled asthma pre-biologic still had incompletely-controlled disease post-biologic-initiation. Predictors of response were outcome-dependent. Lung function-responders were more likely to have higher pre-biologic FeNO (OR:1.20 for every 25ppb increase), and shorter asthma duration (OR:0.81, for every 10-year increase in duration). Higher BEC and presence of T2-related comorbidities were positively associated with higher odds of meeting LTOCS-, control- and lung function-responder criteria.CONCLUSION: Our findings underscore the multi-modal nature of 'response', show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed.",

author = "Ghislaine Scelo and Tran, {Trung N} and Le, {Tham T} and Malin Fareg{\aa}s and Delbert Dorscheid and John Busby and Mona Al-Ahmad and Riyad Al-Lehebi and Alan Altraja and Aaron Beastall and Celine Bergeron and Leif Bjermer and Bjerrum, {Anne S} and Cano-Rosales, {Diana Jimena} and Canonica, {Giorgio Walter} and Victoria Carter and Jeremy Charriot and Christoff, {George C} and Cosio, {Borja G} and Eve Denton and Fernandez-Sanchez, {Maria Jose} and Fonseca, {Jo{\~a}o A} and Gibson, {Peter G} and Celine Goh and Heaney, {Liam G} and Enrico Heffler and Mark Hew and Takashi Iwanaga and Rohit Katial and Koh, {Mariko S} and Piotr Kuna and D{\'e}sir{\'e}e Larenas-Linnemann and Lauri Lehtim{\"a}ki and Bassam Mahboub and Neil Martin and Hisako Matsumoto and Menzies-Gow, {Andrew N} and Papadopoulos, {Nikolaos G} and Pujan Patel and Luis Perez-De-Llano and Matthew Peters and Pfeffer, {Paul E} and Popov, {Todor A} and Porsbjerg, {Celeste M} and Rhee, {Chin K} and Mohsen Sadatsafavi and Camille Taill{\'e} and Torres-Duque, {Carlos A} and Ming-Ju Tsai and Ulrik, {Charlotte S} and Upham, {John W} and {von B{\"u}low}, Anna and Eileen Wang and Wechsler, {Michael E} and Price, {David B}",

note = "Copyright {\textcopyright} 2024. Published by Elsevier Inc.",

year = "2024",

month = sep,

day = "5",

doi = "10.1016/j.jaip.2024.05.016",

language = "English",

volume = "12",

pages = "2347--2361",

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

issn = "2213-2198",

publisher = "American Academy of Allergy, Asthma and Immunology",

number = "9",

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Scelo, G, Tran, TN, Le, TT, Faregås, M, Dorscheid, D, Busby, J, Al-Ahmad, M, Al-Lehebi, R, Altraja, A, Beastall, A, Bergeron, C, Bjermer, L, Bjerrum, AS, Cano-Rosales, DJ, Canonica, GW, Carter, V, Charriot, J, Christoff, GC, Cosio, BG, Denton, E, Fernandez-Sanchez, MJ, Fonseca, JA, Gibson, PG, Goh, C, Heaney, LG, Heffler, E, Hew, M, Iwanaga, T, Katial, R, Koh, MS, Kuna, P, Larenas-Linnemann, D, Lehtimäki, L, Mahboub, B, Martin, N, Matsumoto, H, Menzies-Gow, AN, Papadopoulos, NG, Patel, P, Perez-De-Llano, L, Peters, M, Pfeffer, PE, Popov, TA, Porsbjerg, CM, Rhee, CK, Sadatsafavi, M, Taillé, C, Torres-Duque, CA, Tsai, M-J, Ulrik, CS, Upham, JW, von Bülow, A, Wang, E, Wechsler, ME & Price, DB 2024, 'Exploring definitions and predictors of response to biologics for severe asthma', Journal of Allergy and Clinical Immunology: In Practice, vol. 12, no. 9, pp. 2347-2361. https://doi.org/10.1016/j.jaip.2024.05.016

TY - JOUR

T1 - Exploring definitions and predictors of response to biologics for severe asthma

AU - Scelo, Ghislaine

AU - Tran, Trung N

AU - Le, Tham T

AU - Faregås, Malin

AU - Dorscheid, Delbert

AU - Busby, John

AU - Al-Ahmad, Mona

AU - Al-Lehebi, Riyad

AU - Altraja, Alan

AU - Beastall, Aaron

AU - Bergeron, Celine

AU - Bjermer, Leif

AU - Bjerrum, Anne S

AU - Cano-Rosales, Diana Jimena

AU - Canonica, Giorgio Walter

AU - Carter, Victoria

AU - Charriot, Jeremy

AU - Christoff, George C

AU - Cosio, Borja G

AU - Denton, Eve

AU - Fernandez-Sanchez, Maria Jose

AU - Fonseca, João A

AU - Gibson, Peter G

AU - Goh, Celine

AU - Heaney, Liam G

AU - Heffler, Enrico

AU - Hew, Mark

AU - Iwanaga, Takashi

AU - Katial, Rohit

AU - Koh, Mariko S

AU - Kuna, Piotr

AU - Larenas-Linnemann, Désirée

AU - Lehtimäki, Lauri

AU - Mahboub, Bassam

AU - Martin, Neil

AU - Matsumoto, Hisako

AU - Menzies-Gow, Andrew N

AU - Papadopoulos, Nikolaos G

AU - Patel, Pujan

AU - Perez-De-Llano, Luis

AU - Peters, Matthew

AU - Pfeffer, Paul E

AU - Popov, Todor A

AU - Porsbjerg, Celeste M

AU - Rhee, Chin K

AU - Sadatsafavi, Mohsen

AU - Taillé, Camille

AU - Torres-Duque, Carlos A

AU - Tsai, Ming-Ju

AU - Ulrik, Charlotte S

AU - Upham, John W

AU - von Bülow, Anna

AU - Wang, Eileen

AU - Wechsler, Michael E

AU - Price, David B

PY - 2024/9/5

Y1 - 2024/9/5

N2 - BACKGROUND: Biologic effectiveness is often assessed as 'response', a term which eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in 4 asthma outcome domains were assessed in the 1-year period pre- and post-biologic-initiation in patients with predefined level of pre-biologic impairment. Responder cut-offs were: ≥50% reduction in exacerbation rate, ≥50% reduction in long-term oral corticosteroid [LTOCS] daily dose, ≥1 category improvement in asthma control, and ≥100mL improvement in FEV1. Responders were defined using single- and multiple-domains. The association between pre-biologic characteristics and post-biologic-initiation response were examined by multivariable analysis.RESULTS: 2,210 patients were included. Responder rate ranged from 80.7% (n=566/701) for exacerbation-response to 10.6% (n=9/85) for 4-domain-response. Many responders still exhibited significant impairment post-biologic-initiation: 46.7% (n=206/441) of asthma control-responders with uncontrolled asthma pre-biologic still had incompletely-controlled disease post-biologic-initiation. Predictors of response were outcome-dependent. Lung function-responders were more likely to have higher pre-biologic FeNO (OR:1.20 for every 25ppb increase), and shorter asthma duration (OR:0.81, for every 10-year increase in duration). Higher BEC and presence of T2-related comorbidities were positively associated with higher odds of meeting LTOCS-, control- and lung function-responder criteria.CONCLUSION: Our findings underscore the multi-modal nature of 'response', show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed.

AB - BACKGROUND: Biologic effectiveness is often assessed as 'response', a term which eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in 4 asthma outcome domains were assessed in the 1-year period pre- and post-biologic-initiation in patients with predefined level of pre-biologic impairment. Responder cut-offs were: ≥50% reduction in exacerbation rate, ≥50% reduction in long-term oral corticosteroid [LTOCS] daily dose, ≥1 category improvement in asthma control, and ≥100mL improvement in FEV1. Responders were defined using single- and multiple-domains. The association between pre-biologic characteristics and post-biologic-initiation response were examined by multivariable analysis.RESULTS: 2,210 patients were included. Responder rate ranged from 80.7% (n=566/701) for exacerbation-response to 10.6% (n=9/85) for 4-domain-response. Many responders still exhibited significant impairment post-biologic-initiation: 46.7% (n=206/441) of asthma control-responders with uncontrolled asthma pre-biologic still had incompletely-controlled disease post-biologic-initiation. Predictors of response were outcome-dependent. Lung function-responders were more likely to have higher pre-biologic FeNO (OR:1.20 for every 25ppb increase), and shorter asthma duration (OR:0.81, for every 10-year increase in duration). Higher BEC and presence of T2-related comorbidities were positively associated with higher odds of meeting LTOCS-, control- and lung function-responder criteria.CONCLUSION: Our findings underscore the multi-modal nature of 'response', show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed.

U2 - 10.1016/j.jaip.2024.05.016

DO - 10.1016/j.jaip.2024.05.016

M3 - Article

C2 - 38768896

SN - 2213-2198

VL - 12

SP - 2347

EP - 2361

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

IS - 9

ER -

Exploring definitions and predictors of response to biologics for severe asthma

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