TY - JOUR
T1 - Real-world biologics response and super-response in the International Severe Asthma Registry cohort
AU - the ISAR LUMINANT Working Group
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 Andrés
AU - Al-Lehebi, Riyad
AU - Belhassen, Manon
AU - Bhutani, Mohit
AU - Bosnic-Anticevich, Sinthia Z.
AU - Bourdin, Arnaud
AU - Brusselle, Guy G.
AU - Busby, John
AU - Canonica, Giorgio Walter
AU - Heffler, Enrico
AU - Chapman, Kenneth R.
AU - Charriot, Jérémy
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 - Huang, Erick Wan Chun
AU - Iwanaga, Takashi
AU - Jackson, David J.
AU - Koh, Mariko Siyue
AU - Lehtimäki, Lauri
AU - Máspero, Jorge
AU - Mahboub, Bassam
AU - Menzies-Gow, Andrew N.
AU - Mitchell, Patrick D.
AU - Papadopoulos, Nikolaos G.
AU - Papaioannou, Andriana I.
AU - Perez-de-Llano, Luis
AU - Perng, 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 - Schmid, Johannes Martin
AU - Sheu, Chau-Chyun
AU - Sirena, Concetta
AU - Torres-Duque, Carlos A.
AU - Salameh, Laila
AU - Patel, Pujan H.
AU - Ulrik, Charlotte Suppli
AU - Wang, Eileen
AU - Wechsler, Michael E.
AU - Price, David B.
N1 - Publisher Copyright:
© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2024
Y1 - 2024
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, anti-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.
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, anti-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.
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
AN - SCOPUS:85196741194
SN - 0105-4538
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
ER -