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 Busby, Giorgio 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
{"title":"国际严重哮喘登记队列中的生物制剂真实反应和超级反应。","authors":"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 Busby, Giorgio 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","doi":"10.1111/all.16178","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (FEV<sub>1</sub>) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV<sub>1</sub> increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.</p><p><strong>Results: </strong>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% FEV<sub>1</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":null,"pages":null},"PeriodicalIF":12.6000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Real-world biologics response and super-response in the International Severe Asthma Registry cohort.\",\"authors\":\"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 Busby, Giorgio 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\",\"doi\":\"10.1111/all.16178\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (FEV<sub>1</sub>) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV<sub>1</sub> increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.</p><p><strong>Results: </strong>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% FEV<sub>1</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":122,\"journal\":{\"name\":\"Allergy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.6000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Allergy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/all.16178\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/all.16178","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Real-world biologics response and super-response in the International Severe Asthma Registry cohort.
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.
期刊介绍:
Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality.
Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.