Real-world biologics response and super-response in the International Severe Asthma Registry cohort

Eve Denton; Mark Hew; Matthew J Peters; John W Upham; Lakmini Bulathsinhala; Trung N Tran; Neil  Martin; Celine Bergeron; Mona Al-Ahmad; Alan Altraja; Désirée Larenas-Linnemann; Ruth Murray; Carlos Andres  Celis-Preciado; Riyad  Al-Lehebi; Manon M. Belhassen; Mohit  Bhutani; Sinthia Z  Bosnic-Anticevich; Arnaud Bourdin; Guy  Brusselle; John  Busby; Giorgio Walter Canonica; Enrico Heffler; Kenneth R Chapman; Jeremy  Charriot; George C Christoff; Li Ping  Chung; Borja G. Cosio; Andréanne Côté; Richard W  Costello; Breda Cushen; James Fingleton; João A. Fonseca; Peter G.  Gibson; Liam G Heaney; Erick  Wan-Chun Huang; Takashi Iwanaga; David J Jackson; Mariko Siyue Koh; Lauri Lehtimäki; Jorge  Máspero; Bassam Mahboub; Andrew Menzies-Gow; Patrick Mitchell; Nikolaos G Papadopoulos; Andriana I. Papaioannou; Luis  Perez-De-Llano; Diahn-Warng Perng Steve; Paul E Pfeffer; Todor A Popov; Celeste M. Porsbjerg; Chin Kook Rhee; Nicolas Roche; Mohsen Sadatsafavi; Sundeep Salvi; Johannes  Martin Schmid; Chau-Chyun  Sheu; Concetta Sirena; Carlos A.  Torres-Duque; Laila Salameh; Pujan H  Patel; Charlotte  Suppli Ulrik; Eileen Wang; Michael E Wechsler; David Price; ISAR LUMINANT

doi:10.1111/all.16178

Real-world biologics response and super-response in the International Severe Asthma Registry cohort

Eve Denton, Mark Hew, Matthew J Peters, John W Upham, Lakmini Bulathsinhala, Trung N Tran, Neil Martin, Celine Bergeron , Mona Al-Ahmad, Alan Altraja, Désirée Larenas-Linnemann, Ruth Murray, Carlos Andres Celis-Preciado, Riyad Al-Lehebi, Manon M. Belhassen, Mohit Bhutani, Sinthia Z Bosnic-Anticevich, Arnaud Bourdin, Guy Brusselle, John BusbyGiorgio Walter Canonica, Enrico Heffler, Kenneth R Chapman, Jeremy Charriot, George C Christoff, Li Ping Chung, Borja G. Cosio, Andréanne Côté, Richard W Costello, Breda Cushen, James Fingleton, João A. Fonseca, Peter G. Gibson, Liam G Heaney, Erick Wan-Chun Huang, Takashi Iwanaga, David J Jackson, Mariko Siyue Koh, Lauri Lehtimäki, Jorge Máspero, Bassam Mahboub, Andrew Menzies-Gow, Patrick Mitchell, Nikolaos G Papadopoulos, Andriana I. Papaioannou, Luis Perez-De-Llano, Diahn-Warng Perng Steve, Paul E Pfeffer, Todor A Popov, Celeste M. Porsbjerg, Chin Kook Rhee, Nicolas Roche, Mohsen Sadatsafavi, Sundeep Salvi, Johannes Martin Schmid, Chau-Chyun Sheu, Concetta Sirena, Carlos A. Torres-Duque, Laila Salameh, Pujan H Patel, Charlotte Suppli Ulrik, Eileen Wang, Michael E Wechsler, David Price^* (Corresponding Author), ISAR LUMINANT

^*Corresponding author for this work

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

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Abstract

Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.
Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti422 IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.
Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics.
Biologic initiators had worse baseline impairment than non-initiators, despite having similar
biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54%
FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and
39%, respectively, were super-responses. Responses/super-responses were more frequent in
biologic initiators than in non-initiators; nevertheless, ~40–50% of initiators did not meet response criteria.
Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies.
Biologics are initiated in patients who have worse baseline impairments than non-initiators
despite similar biomarker levels. Although biologic initiators exhibited clinical responses and
super-responses in all outcome domains, 40–50% did not meet the response criteria

Original language	English
Pages (from-to)	2700-2716
Number of pages	17
Journal	Allergy
Volume	79
Issue number	10
Early online date	22 Jun 2024
DOIs	https://doi.org/10.1111/all.16178
Publication status	Published - Oct 2024

Bibliographical note

The authors thank Dr David Neil (PhD) of the Observational and Pragmatic Research Institute (OPRI), Ms Pui Yee Lai (MA) of OPRI, and Ms Andrea Lim (BSc, Hons) of OPRI, for editorial support, which was funded by the Observational and Pragmatic Research Institute Pte. Ltd. Finally, a big thank you to our International Severe Asthma Registry collaborators (see online Supplement in Data S1). collaborators (see
online Supplement).

Data Availability Statement

The de-identified data collected for LUMINANT may be made available to entities wishing to perform appropriate, ethics-approved analyses after approval of the protocol by the International Severe Asthma Registry Steering Committee, with an appropriate signed data access agreement. The LUMINANT study protocol will be made available upon reasonable request to the corresponding author.

Keywords

Asthma
Biologics
Clinical response
International Severe Asthma Registry (ISAR)
Monoclonal antibodies
Super-responders

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Denton, E., Hew, M., Peters, M. J., Upham, J. W., Bulathsinhala, L., Tran, T. N., Martin, N., Bergeron , C., Al-Ahmad, M., Altraja, A., Larenas-Linnemann, D., Murray, R., Celis-Preciado, C. A., Al-Lehebi, R., Belhassen, M. M., Bhutani, M., Bosnic-Anticevich, S. Z., Bourdin, A., Brusselle, G., ... ISAR LUMINANT (2024). Real-world biologics response and super-response in the International Severe Asthma Registry cohort. Allergy, 79(10), 2700-2716. https://doi.org/10.1111/all.16178

Denton, E, Hew, M, Peters, MJ, Upham, JW, Bulathsinhala, L, Tran, TN, Martin, N, Bergeron , C, Al-Ahmad, M, Altraja, A, Larenas-Linnemann, D, Murray, R, Celis-Preciado, CA, Al-Lehebi, R, Belhassen, MM, Bhutani, M, Bosnic-Anticevich, SZ, Bourdin, A, Brusselle, G, Busby, J, Canonica, GW, Heffler, E, Chapman, KR, Charriot, J, Christoff, GC, Chung, LP, Cosio, BG, Côté, A, Costello, RW, Cushen, B, Fingleton, J, Fonseca, JA, Gibson, PG, Heaney, LG, Wan-Chun Huang, E, Iwanaga, T, Jackson, DJ, Koh, MS, Lehtimäki, L, Máspero, J, Mahboub, B, Menzies-Gow, A, Mitchell, P, Papadopoulos, NG, Papaioannou, AI, Perez-De-Llano, L, Perng Steve, D-W, Pfeffer, PE, Popov, TA, Porsbjerg, CM, Rhee, CK, Roche, N, Sadatsafavi, M, Salvi, S, Martin Schmid, J, Sheu, C-C, Sirena, C, Torres-Duque, CA, Salameh, L, Patel, PH, Suppli Ulrik, C, Wang, E, Wechsler, ME, Price, D & ISAR LUMINANT 2024, 'Real-world biologics response and super-response in the International Severe Asthma Registry cohort', Allergy, vol. 79, no. 10, pp. 2700-2716. https://doi.org/10.1111/all.16178

@article{83ade39b787e4fd583fa0c94509d7be8,

title = "Real-world biologics response and super-response in the International Severe Asthma Registry cohort",

abstract = "Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti422 IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics.Biologic initiators had worse baseline impairment than non-initiators, despite having similarbiomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54%FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and39%, respectively, were super-responses. Responses/super-responses were more frequent inbiologic initiators than in non-initiators; nevertheless, ~40–50% of initiators did not meet response criteria.Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies.Biologics are initiated in patients who have worse baseline impairments than non-initiatorsdespite similar biomarker levels. Although biologic initiators exhibited clinical responses andsuper-responses in all outcome domains, 40–50% did not meet the response criteria",

keywords = "Asthma, Biologics, Clinical response, International Severe Asthma Registry (ISAR), Monoclonal antibodies, Super-responders",

author = "Eve Denton and Mark Hew and Peters, {Matthew J} and Upham, {John W} and Lakmini Bulathsinhala and Tran, {Trung N} and Neil Martin and Celine Bergeron and Mona Al-Ahmad and Alan Altraja and D{\'e}sir{\'e}e Larenas-Linnemann and Ruth Murray and Celis-Preciado, {Carlos Andres} and Riyad Al-Lehebi and Belhassen, {Manon M.} and Mohit Bhutani and Bosnic-Anticevich, {Sinthia Z} and Arnaud Bourdin and Guy Brusselle and John Busby and Canonica, {Giorgio Walter} and Enrico Heffler and Chapman, {Kenneth R} and Jeremy Charriot and Christoff, {George C} and Chung, {Li Ping} and Cosio, {Borja G.} and Andr{\'e}anne C{\^o}t{\'e} and Costello, {Richard W} and Breda Cushen and James Fingleton and Fonseca, {Jo{\~a}o A.} and Gibson, {Peter G.} and Heaney, {Liam G} and {Wan-Chun Huang}, Erick and Takashi Iwanaga and Jackson, {David J} and Koh, {Mariko Siyue} and Lauri Lehtim{\"a}ki and Jorge M{\'a}spero and Bassam Mahboub and Andrew Menzies-Gow and Patrick Mitchell and Papadopoulos, {Nikolaos G} and Papaioannou, {Andriana I.} and Luis Perez-De-Llano and {Perng Steve}, Diahn-Warng and Pfeffer, {Paul E} and Popov, {Todor A} and Porsbjerg, {Celeste M.} and Rhee, {Chin Kook} and Nicolas Roche and Mohsen Sadatsafavi and Sundeep Salvi and {Martin Schmid}, Johannes and Chau-Chyun Sheu and Concetta Sirena and Torres-Duque, {Carlos A.} and Laila Salameh and Patel, {Pujan H} and {Suppli Ulrik}, Charlotte and Eileen Wang and Wechsler, {Michael E} and David Price and {ISAR LUMINANT}",

note = "The authors thank Dr David Neil (PhD) of the Observational and Pragmatic Research Institute (OPRI), Ms Pui Yee Lai (MA) of OPRI, and Ms Andrea Lim (BSc, Hons) of OPRI, for editorial support, which was funded by the Observational and Pragmatic Research Institute Pte. Ltd. Finally, a big thank you to our International Severe Asthma Registry collaborators (see online Supplement in Data S1). collaborators (see online Supplement).",

year = "2024",

month = oct,

doi = "10.1111/all.16178",

language = "English",

volume = "79",

pages = "2700--2716",

journal = "Allergy",

issn = "0105-4538",

publisher = "John Wiley & Sons, Ltd (10.1111)",

number = "10",

}

TY - JOUR

T1 - Real-world biologics response and super-response in the International Severe Asthma Registry cohort

AU - Denton, Eve

AU - Hew, Mark

AU - Peters, Matthew J

AU - Upham, John W

AU - Bulathsinhala, Lakmini

AU - Tran, Trung N

AU - Martin, Neil

AU - Bergeron , Celine

AU - Al-Ahmad, Mona

AU - Altraja, Alan

AU - Larenas-Linnemann, Désirée

AU - Murray, Ruth

AU - Celis-Preciado, Carlos Andres

AU - Al-Lehebi, Riyad

AU - Belhassen, Manon M.

AU - Bhutani, Mohit

AU - Bosnic-Anticevich, Sinthia Z

AU - Bourdin, Arnaud

AU - Brusselle, Guy

AU - Busby, John

AU - Canonica, Giorgio Walter

AU - Heffler, Enrico

AU - Chapman, Kenneth R

AU - Charriot, Jeremy

AU - Christoff, George C

AU - Chung, Li Ping

AU - Cosio, Borja G.

AU - Côté, Andréanne

AU - Costello, Richard W

AU - Cushen, Breda

AU - Fingleton, James

AU - Fonseca, João A.

AU - Gibson, Peter G.

AU - Heaney, Liam G

AU - Wan-Chun Huang, Erick

AU - Iwanaga, Takashi

AU - Jackson, David J

AU - Koh, Mariko Siyue

AU - Lehtimäki, Lauri

AU - Máspero, Jorge

AU - Mahboub, Bassam

AU - Menzies-Gow, Andrew

AU - Mitchell, Patrick

AU - Papadopoulos, Nikolaos G

AU - Papaioannou, Andriana I.

AU - Perez-De-Llano, Luis

AU - Perng Steve, Diahn-Warng

AU - Pfeffer, Paul E

AU - Popov, Todor A

AU - Porsbjerg, Celeste M.

AU - Rhee, Chin Kook

AU - Roche, Nicolas

AU - Sadatsafavi, Mohsen

AU - Salvi, Sundeep

AU - Martin Schmid, Johannes

AU - Sheu, Chau-Chyun

AU - Sirena, Concetta

AU - Torres-Duque, Carlos A.

AU - Salameh, Laila

AU - Patel, Pujan H

AU - Suppli Ulrik, Charlotte

AU - Wang, Eileen

AU - Wechsler, Michael E

AU - Price, David

AU - ISAR LUMINANT

N1 - The authors thank Dr David Neil (PhD) of the Observational and Pragmatic Research Institute (OPRI), Ms Pui Yee Lai (MA) of OPRI, and Ms Andrea Lim (BSc, Hons) of OPRI, for editorial support, which was funded by the Observational and Pragmatic Research Institute Pte. Ltd. Finally, a big thank you to our International Severe Asthma Registry collaborators (see online Supplement in Data S1). collaborators (see online Supplement).

PY - 2024/10

Y1 - 2024/10

N2 - Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti422 IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics.Biologic initiators had worse baseline impairment than non-initiators, despite having similarbiomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54%FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and39%, respectively, were super-responses. Responses/super-responses were more frequent inbiologic initiators than in non-initiators; nevertheless, ~40–50% of initiators did not meet response criteria.Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies.Biologics are initiated in patients who have worse baseline impairments than non-initiatorsdespite similar biomarker levels. Although biologic initiators exhibited clinical responses andsuper-responses in all outcome domains, 40–50% did not meet the response criteria

AB - Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti422 IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics.Biologic initiators had worse baseline impairment than non-initiators, despite having similarbiomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54%FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and39%, respectively, were super-responses. Responses/super-responses were more frequent inbiologic initiators than in non-initiators; nevertheless, ~40–50% of initiators did not meet response criteria.Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies.Biologics are initiated in patients who have worse baseline impairments than non-initiatorsdespite similar biomarker levels. Although biologic initiators exhibited clinical responses andsuper-responses in all outcome domains, 40–50% did not meet the response criteria

KW - Asthma

KW - Biologics

KW - Clinical response

KW - International Severe Asthma Registry (ISAR)

KW - Monoclonal antibodies

KW - Super-responders

U2 - 10.1111/all.16178

DO - 10.1111/all.16178

M3 - Article

SN - 0105-4538

VL - 79

SP - 2700

EP - 2716

JO - Allergy

JF - Allergy

IS - 10

ER -

Real-world biologics response and super-response in the International Severe Asthma Registry cohort

Abstract

Bibliographical note

Data Availability Statement

Keywords

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