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

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

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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
Number of pages	111
Journal	Journal of Allergy and Clinical Immunology: In Practice
DOIs	https://doi.org/10.1016/j.jaip.2024.05.016 https://doi.org/10.1016/j.jaip.2024.05.016
State	Published - 13 May 2024

Keywords

anti-IgE
anti-IL5/5R
anti-IL4Rα
control
exacerbation
lung function
oral corticosteroid

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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. https://doi.org/10.1016/j.jaip.2024.05.016, https://doi.org/10.1016/j.jaip.2024.05.016

@article{66df9dfc8ac543ce82ce037e0fae777c,

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

abstract = "Background: Biologic effectiveness is often assessed as {\textquoteleft}response{\textquoteright}, 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 {\textquoteleft}response{\textquoteright}, show that many responders experience residual symptoms post-biologic-initiation, and that predictors of response vary according to outcome assessed.",

keywords = "anti-IgE, anti-IL5/5R, anti-IL4Rα, control, exacerbation, lung function, oral corticosteroid",

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 Carlos.a. Torres-Duque 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.}",

year = "2024",

month = may,

day = "13",

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

language = "English",

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

issn = "2213-2198",

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

}

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. https://doi.org/10.1016/j.jaip.2024.05.016, 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 - 2024/5/13

Y1 - 2024/5/13

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.

KW - anti-IgE

KW - anti-IL5/5R

KW - anti-IL4Rα

KW - control

KW - exacerbation

KW - lung function

KW - oral corticosteroid

U2 - 10.1016/j.jaip.2024.05.016

DO - 10.1016/j.jaip.2024.05.016

M3 - Article

SN - 2213-2198

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

ER -

Exploring definitions and predictors of response to biologics for severe asthma

Abstract

Keywords

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