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Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.
Porsbjerg, Celeste M; Townend, John; Bergeron, Celine; Christoff, George C; Katsoulotos, Gregory P; Larenas-Linnemann, Désirée; Tran, Trung N; Al-Lehebi, Riyad; Bosnic-Anticevich, Sinthia Z; Busby, John; Hew, Mark; Kostikas, Konstantinos; Papadopoulos, Nikolaos G; Pfeffer, Paul E; Popov, Todor A; Rhee, Chin Kook; Sadatsafavi, Mohsen; Tsai, Ming-Ju; Ulrik, Charlotte Suppli; Al-Ahmad, Mona; Altraja, Alan; Beastall, Aaron; Bulathsinhala, Lakmini; Carter, Victoria; Cosio, Borja G; Fletton, Kirsty; Hansen, Susanne; Heaney, Liam G; Hubbard, Richard B; Kuna, Piotr; Murray, Ruth B; Nagano, Tatsuya; Pini, Laura; Cano Rosales, Diana Jimena; Schleich, Florence; Wechsler, Michael E; Amaral, Rita; Bourdin, Arnaud; Brusselle, Guy G; Chen, Wenjia; Chung, Li Ping; Denton, Eve; Fonseca, Joao A; Hoyte, Flavia; Jackson, David J; Katial, Rohit; Kirenga, Bruce J; Koh, Mariko Siyue; Lawkiedraj, Agnieszka; Lehtimäki, Lauri.
Afiliación
  • Porsbjerg CM; Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
  • Townend J; Observational and Pragmatic Research Institute, Singapore, Singapore.
  • Bergeron C; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Christoff GC; Department of Medicine, Centre for Lung Health, Vancouver General Hospital, Vancouver, BC, Canada.
  • Katsoulotos GP; Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.
  • Larenas-Linnemann D; Faculty of Public Health, Medical University, Sofia, Bulgaria.
  • Tran TN; Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.
  • Al-Lehebi R; School of Medicine, Sydney Campus, The University of Notre Dame, Sydney, NSW, Australia.
  • Bosnic-Anticevich SZ; Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico.
  • Busby J; BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, United States.
  • Hew M; Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia.
  • Kostikas K; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
  • Papadopoulos NG; Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.
  • Pfeffer PE; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Popov TA; Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
  • Rhee CK; Allergy, Asthma and Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia.
  • Sadatsafavi M; Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
  • Tsai MJ; Respiratory Medicine Department, University of Ioannina, Ioannina, Greece.
  • Ulrik CS; Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, United Kingdom.
  • Al-Ahmad M; Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
  • Altraja A; Department of Respiratory Medicine, Barts Health National Health Services (NHS) Trust, London, United Kingdom.
  • Beastall A; Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Bulathsinhala L; University Hospital St. Ivan Rilski, Sofia, Bulgaria.
  • Carter V; 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, Republic of Korea.
  • Cosio BG; Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
  • Fletton K; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Hansen S; Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Heaney LG; Department of Respiratory Medicine, Copenhagen ;University Hospital - Hvidovre, Copenhagen, Denmark.
  • Hubbard RB; Microbiology Department, College of Medicine, Kuwait University, Kuwait City, Kuwait.
  • Kuna P; Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait.
  • Murray RB; Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia.
  • Nagano T; Observational and Pragmatic Research Institute, Singapore, Singapore.
  • Pini L; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Cano Rosales DJ; Observational and Pragmatic Research Institute, Singapore, Singapore.
  • Schleich F; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Wechsler ME; Observational and Pragmatic Research Institute, Singapore, Singapore.
  • Amaral R; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Bourdin A; Son Espases University Hospital-Institut d'Investigació Sanitària Illes Balears (IdISBa)-Ciberes, Mallorca, Spain.
  • Brusselle GG; Observational and Pragmatic Research Institute, Singapore, Singapore.
  • Chen W; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Chung LP; Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
  • Denton E; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
  • Fonseca JA; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom.
  • Hoyte F; Observational and Pragmatic Research Institute, Singapore, Singapore.
  • Jackson DJ; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Katial R; Respiratory Medicine at the School of Medicine, University of Nottingham, Nottingham, United Kingdom.
  • Kirenga BJ; Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland.
  • Koh MS; Optimum Patient Care Global, Cambridge, United Kingdom.
  • Lawkiedraj A; Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
  • Lehtimäki L; Department of Clinical and Experimental Sciences - University of Brescia, Spedali Civili di Brescia, Brescia, Italy.
Front Immunol ; 15: 1361891, 2024.
Article en En | MEDLINE | ID: mdl-38711495
ABSTRACT

Background:

To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.

Aim:

To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.

Methods:

This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.

Results:

Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2 0.751), compared to BEC (adjusted R2 0.747) or FeNO alone (adjusted R2 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE.

Conclusions:

The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Productos Biológicos / Inmunoglobulina E / Biomarcadores / Eosinófilos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Productos Biológicos / Inmunoglobulina E / Biomarcadores / Eosinófilos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza