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 Andrés Celis-Preciado, Riyad Al-Lehebi, Manon Belhassen, Mohit Bhutani, Sinthia Z. Bosnic-Anticevich, Arnaud Bourdin, Guy G. Brusselle, John BusbyGiorgio Walter Canonica, Enrico Heffler, Kenneth R. Chapman, Jérémy 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 N. Menzies-Gow, Patrick D. Mitchell, Nikolaos G. Papadopoulos, Andriana I. Papaioannou, Luis Perez-de-Llano, Diahn Warng Perng, 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 B. Price*, the ISAR LUMINANT Working Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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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, 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.

Original languageEnglish
Pages (from-to)2700-2716
Number of pages17
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume79
Issue number10
Early online date22 Jun 2024
DOIs
Publication statusPublished - Oct 2024

Bibliographical note

Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • asthma
  • biologics
  • clinical response
  • International Severe Asthma Registry (ISAR)
  • monoclonal antibodies
  • super-responders

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