Exploring definitions and predictors of response to biologics for severe asthma.

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

Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
18 May 2024
Historique:
received: 04 12 2023
revised: 19 04 2024
accepted: 13 05 2024
medline: 21 5 2024
pubmed: 21 5 2024
entrez: 20 5 2024
Statut: aheadofprint

Résumé

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

Sections du résumé

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

Identifiants

pubmed: 38768896
pii: S2213-2198(24)00530-0
doi: 10.1016/j.jaip.2024.05.016
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Ghislaine Scelo (G)

Observational and Pragmatic Research Institute, Singapore, (Singapore); Optimum Patient Care Global, Cambridge (UK).

Trung N Tran (TN)

BioPharmaceuticals Medical, AstraZeneca - Gaithersburg, MD (USA).

Tham T Le (TT)

BioPharmaceuticals Medical, AstraZeneca - Gaithersburg, MD (USA).

Malin Faregås (M)

BioPharmaceuticals Medical, AstraZeneca - Gothenburg (Sweden); BioPharmaceuticals Medical, AstraZeneca - Gaithersburg, MD (USA).

Delbert Dorscheid (D)

Center for Heart Lung Innovation, University of British Columbia, (Canada).

John Busby (J)

Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University - Belfast (UK).

Mona Al-Ahmad (M)

Microbiology Department, College of Medicine, Kuwait University; Al-Rashed Allergy Center, Ministry of Health - Kuwait (Kuwait).

Riyad Al-Lehebi (R)

Department of Pulmonology, King Fahad Medical City; Alfaisal University - Riyadh (Saudi Arabia); College of Medicine, Alfaisal University, Riyadh, (Saudi Arabia).

Alan Altraja (A)

Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, (Estonia).

Aaron Beastall (A)

Optimum Patient Care Global, Cambridge (UK).

Celine Bergeron (C)

Centre for Lung Health, Vancouver General Hospital and University of British Columbia, Vancouver (Canada).

Leif Bjermer (L)

Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, (Sweden).

Anne S Bjerrum (AS)

Department of Respiratory Medicine and Allergy, Aarhus University Hospital, (Denmark).

Diana Jimena Cano-Rosales (DJ)

Instituto Neumológico del Oriente, Bucaramanga, Santander, (Colombia).

Giorgio Walter Canonica (GW)

Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano (Italy); Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan (Italy).

Victoria Carter (V)

Observational and Pragmatic Research Institute, Singapore, (Singapore); Optimum Patient Care Global, Cambridge (UK).

Jeremy Charriot (J)

PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, (France).

George C Christoff (GC)

Medical University - Sofia (Bulgaria).

Borja G Cosio (BG)

Son Espases University Hospital-IdISBa-Ciberes, Mallorca (Spain).

Eve Denton (E)

Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, (Australia); Department of Medicine, Central Clinical School, Monash University, (Australia).

Maria Jose Fernandez-Sanchez (MJ)

Pulmonary Unit, Hospital Universitario San Ignacio, Bogota, (Colombia); Faculty of Medicine, Pontificia Universidad Javeriana, Bogota (Colombia).

João A Fonseca (JA)

CINTESIS@RISE, MEDCIDS, Faculty of Medicine of the University of Porto - Porto (Portugal).

Peter G Gibson (PG)

Australian Severe Asthma Network, Priority Research Centre for Healthy Lungs, University of Newcastle; Hunter Medical Research Institute, Department of Respiratory and Sleep Medicine, John Hunter Hospital - Newcastle (Australia).

Celine Goh (C)

Observational and Pragmatic Research Institute, Singapore, (Singapore); Optimum Patient Care Global, Cambridge (UK).

Liam G Heaney (LG)

Wellcome-Wolfson Institute for Experimental Medicine, Queen's University - Belfast (UK).

Enrico Heffler (E)

Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano (Italy); Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan (Italy).

Mark Hew (M)

Allergy, Asthma & Clinical Immunology Service, Alfred Health; Public Health and Preventive Medicine, Monash University - Melbourne (Australia).

Takashi Iwanaga (T)

Kindai University Hospital - Osakasayama (Japan).

Rohit Katial (R)

Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, (USA).

Mariko S Koh (MS)

Department of Respiratory and Critical Care Medicine, Singapore General Hospital - Singapore (Singapore).

Piotr Kuna (P)

Division of Internal Medicine Asthma and Allergy, Medical University of Lodz - Lodz (Poland).

Désirée Larenas-Linnemann (D)

Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México - Mexico (Mexico).

Lauri Lehtimäki (L)

Allergy Centre, Tampere University Hospital, Tampere, (Finland); Faculty of Medicine and Health Technology, Tampere University, Tampere, (Finland).

Bassam Mahboub (B)

Rashid hospital, Dubai Health Authority (DHA) - Dubai (Utd.Arab Emir.).

Neil Martin (N)

BioPharmaceuticals Medical, AstraZeneca - Cambridge (UK).

Hisako Matsumoto (H)

Department of Respiratory Medicine & Allergology, Kindai University Faculty of Medicine, (Japan).

Andrew N Menzies-Gow (AN)

BioPharmaceuticals Medical, AstraZeneca - Cambridge (UK).

Nikolaos G Papadopoulos (NG)

Centre for Respiratory Medicine & Allergy, Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, (UK); Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens (Greece).

Pujan Patel (P)

Respiratory Medicine, Royal Brompton Hospital, London, (UK).

Luis Perez-De-Llano (L)

Pneumology Service. Lucus Augusti University Hospital. EOXI Lugo, Monforte, Cervo (Spain).

Matthew Peters (M)

Department of Thoracic Medicine, Concord Hospital, Sydney (Australia).

Paul E Pfeffer (PE)

Department of Respiratory Medicine, Barts Health NHS Trust, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (UK).

Todor A Popov (TA)

University Hospital Sv. Ivan Rilski, Sofia (Bulgaria).

Celeste M Porsbjerg (CM)

Bispebjerg Hospital, Department of Respiratory Medicine and Infections Diseases, Research Unit - Copenhagen (Denmark).

Chin K Rhee (CK)

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea - Seoul (South Korea).

Mohsen Sadatsafavi (M)

Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia - Vancouver (Canada).

Camille Taillé (C)

Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université Paris Cité, Paris, (France).

Carlos A Torres-Duque (CA)

CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana - Bogotá (Colombia).

Ming-Ju Tsai (MJ)

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, (Taiwan); Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, (Taiwan).

Charlotte S Ulrik (CS)

Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, (Denmark).

John W Upham (JW)

Frazer Institute & PA-Southside Clinical Unit, The University of Queensland, Brisbane, (Australia).

Anna von Bülow (A)

Respiratory Research Unit - Hvidovre, Department of Respiratory Medicine and Infectious Diseases, Bispebjerg hospital, Copenhagen, (Denmark).

Eileen Wang (E)

National Jewish Health and University of Colorado School of Medicine - Denver and Aurora (USA).

Michael E Wechsler (ME)

NJH Cohen Family Asthma Institute, Department of Medicine, National Jewish Health, Denver (USA).

David B Price (DB)

Observational and Pragmatic Research Institute, Singapore, (Singapore); Optimum Patient Care Global, Cambridge (UK); Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen (UK). Electronic address: dprice@opri.sg.

Classifications MeSH