Comparative effectiveness of Anti-IL5 and Anti-IgE biologic classes in patients with severe asthma eligible for both
Paul E Pfeffer 1 2, Nasloon Ali 3 4, Ruth Murray 4, Charlotte Ulrik 5, Trung N Tran 6, Jorge Maspero 7 8, Matthew Peters 9, George C Christoff 10, Mohsen Sadatsafavi 11, Carlos A Torres-Duque 12, Alan Altraja 13, Lauri Lehtimäki 14 15, Nikolaos G Papadopoulos 16 17, Sundeep Salvi 18, Richard W Costello 19, Breda Cushen 20, Enrico Heffler 21 22, Takashi Iwanaga 23, Mona Al-Ahmad 24, Désirée Larenas-Linnemann 25, Piotr Kuna 26, João A Fonseca 27, Riyad Al-Lehebi 28 29, Chin Kook Rhee 30, Luis Perez-de-Llano 31 32, Diahn-Warng Perng Steve 33 34, Bassam Mahboub 35 36, Eileen Wang 37 38, Celine Goh 3 4, Juntao Lyu 3 39, Anthony Newell 3 39, Marianna Alacqua 40, Andrey S Belevskiy 41, Mohit Bhutani 42, Leif Bjermer 43, Unnur Bjornsdottir 44, Arnaud Bourdin 45, Anna von Bulow 46, John Busby 47, Giorgio Walter Canonica 21 22, Borja G Cosio 48, Delbert R Dorscheid 49, Mariana Muñoz-Esquerre 50 51, J Mark FitzGerald 52, Esther Garcia Gil 53, Peter G Gibson 54 55, Liam G Heaney 56, Mark Hew 57 58, Ole Hilberg 59, Flavia Hoyte 37 38, David J Jackson 60 61, Mariko Siyue Koh 62 63, Hsin-Kuo Bruce Ko 64, Jae Ha Lee 65, Sverre Lehmann 66 67, Cláudia Chaves Loureiro 68, Dóra Lúðvíksdóttir 69 70, Andrew N Menzies-Gow 71, Patrick Mitchell 72, Andriana I Papaioannou 73, Todor A Popov 74, Celeste M Porsbjerg 75, Laila Salameh 35 36, Concetta Sirena 76, Camille Taillé 77, Christian Taube 78, Yuji Tohda 79, Michael E Wechsler 80, David B Price 3 4 81
Affiliations
Affiliations
- Department of Respiratory Medicine, Barts Health NHS Trust, London, UK.
- 2Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- 3Observational and Pragmatic Research Institute, Singapore, Singapore.
- 4Optimum Patient Care Global, Cambridge, UK.
- 5Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark.
- 6AstraZeneca, Gaithersburg, Maryland, USA.
- 7Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina.
- 8University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina.
- 9Department of Thoracic Medicine, Concord Hospital, Sydney, Australia.
- 10Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria.
- 11Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
- 12CINEUMO, Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia.
- 13Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia.
- 14Allergy Centre, Tampere University Hospital, Tampere, Finland.
- 15Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
- 16Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
- 17Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
- 18Pulmocare Research and Education Foundation, Pune, India.
- 19Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, Dublin, Ireland.
- 20Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland.
- 21Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy.
- 22Department of Biomedical Sciences, Humanitas University, Milan, Italy.
- 23Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan.
- 24Microbiology Department, College of Medicine, Kuwait University, Kuwait, Al-Rashed Allergy Center, Kuwait, Kuwait.
- 25Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico.
- 26Division of Internal Medicine, Asthma and Allergy Medical University of Łódź, Łódź, Poland.
- 27Health Information and Decision Sciences Department (MEDCIDS), CINTESIS@RiSE, Faculty of Medicine of University of Porto, Porto, Portugal.
- 28Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia. Alfaisal University, Riyadh, Saudi Arabia.
- 29Alfaisal University, Riyadh, Saudi Arabia.
- 30Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
- 31Pneumology Service, Lucus Augusti University Hospital, Cervo, Spain.
- 32Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago, Spain.
- 33Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
- 34COPD Assembly of the Asian Pacific Society of Respirology, Hong Kong, China.
- 35College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
- 36Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
- 37Department of Medicine, Division of Allergy & Clinical Immunology, National Jewish Health, Denver, Colorado, USA.
- 38Department of Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.
- 39Optimum Patient Care, Queensland, Australia.
- 40CSL Behring SpA, Milan, Italy.
- 41Department of Pulmonology, N.I. Pirogov Russian State National Research Medical University, Moscow, Russian Federation.
- 42Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Edmonton, Canada.
- 43Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden.
- 44Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland.
- 45PhyMedExp, Univ Montpellier, CNRS, INSERM, Montpellier, France.
- 46Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
- 47Centre for Public Health, Queen's University Belfast, Belfast, UK.
- 48Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain.
- 49Department of Medicine, Center for Heart, Lung Innovation, The University of British Columbia, Vancouver, Canada.
- 50Department of Respiratory Medicine, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
- 51University of Barcelona, Barcelona, Spain.
- 52Department of Medicine, The University of British Columbia, Vancouver, Canada.
- 53AstraZeneca, Barcelona, Spain.
- 54Australian Severe Asthma Network, Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia.
- 55Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, New Lambton Heights, Australia.
- 56Wellcome-Wolfson Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.
- 57Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia.
- 58Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
- 59Medical department, Vejle University Hospital, Vejle, Denmark.
- 60UK Severe Asthma Network and National Registry, Guy's and St Thomas' NHS Trust, London, England.
- 61School of Immunology & Microbial Sciences, King's College London, London, UK.
- 62Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.
- 63SingHealth Duke-NUS Lung Centre, Singapore, Singapore.
- 64Department of Chest Medicine, Division of Respiratory Therapy, Taipei Veterans General Hospital, Taipei, Taiwan.
- 65Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
- 66Department of Clinical Science, Section of Thoracic Medicine, University of Bergen, Bergen, Norway.
- 67Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
- 68Pulmonology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal & Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
- 69Department of Allergy, University Hospital, Reykjavik, Iceland.
- 70Department of Respiratory Medicine, University Hospital, Reykjavik, Iceland.
- 71Royal Brompton & Harefield Hospitals, London, UK.
- 72School of Medicine, Trinity College Dublin, Dublin, Ireland.
- 732nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece.
- 74University Hospital "Sv. Ivan Rilski", Sofia, Bulgaria.
- 75Department of Respiratory Medicine and Infections Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
- 76Severe Asthma Network Italy (SANI), Milan, Italy.
- 77Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France.
- 78Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany.
- 79Kindai University Hospital, Osakasayama, Japan.
- 80NJH Cohen Family Asthma Institute, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
- 81Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
Abstract
Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life.
Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions.
Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43).
Conclusions: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.
Keywords: ISAR; biologics; exacerbation; oral corticosteroids; real life.
Similar articles
Chen W, Sadatsafavi M, Tran TN, Murray RB, Wong CBN, Ali N, Ariti C, Garcia Gil E, Newell A, Alacqua M, Al-Ahmad M, Altraja A, Al-Lehebi R, Bhutani M, Bjermer L, Bjerrum AS, Bourdin A, Bulathsinhala L, von Bülow A, Busby J, Canonica GW, Carter V, Christoff GC, Cosio BG, Costello RW, FitzGerald JM, Fonseca JA, Yoo KH, Heaney LG, Heffler E, Hew M, Hilberg O, Hoyte F, Iwanaga T, Jackson DJ, Jones RC, Koh MS, Kuna P, Larenas-Linnemann D, Lehmann S, Lehtimäki LA, Lyu J, Mahboub B, Maspero J, Menzies-Gow AN, Sirena C, Papadopoulos N, Papaioannou AI, Pérez de Llano L, Perng DW, Peters M, Pfeffer PE, Porsbjerg CM, Popov TA, Rhee CK, Salvi S, Taillé C, Taube C, Torres-Duque CA, Ulrik CS, Ra SW, Wang E, Wechsler ME, Price DB.J Asthma Allergy. 2022 Oct 21;15:1491-1510. doi: 10.2147/JAA.S377174. eCollection 2022.PMID: 36303891 Free PMC article.
A comparison of biologicals in the treatment of adults with severe asthma - real-life experiences.
Kotisalmi E, Hakulinen A, Mäkelä M, Toppila-Salmi S, Kauppi P.Asthma Res Pract. 2020 May 13;6:2. doi: 10.1186/s40733-020-00055-9. eCollection 2020.PMID: 32467765 Free PMC article.
Martínez-Moragón E, García-Moguel I, Nuevo J, Resler G; ORBE study investigators.BMC Pulm Med. 2021 Dec 18;21(1):417. doi: 10.1186/s12890-021-01785-z.PMID: 34922515 Free PMC article.
Anti-IL5 therapies for asthma.
Farne HA, Wilson A, Powell C, Bax L, Milan SJ.Cochrane Database Syst Rev. 2017 Sep 21;9(9):CD010834. doi: 10.1002/14651858.CD010834.pub3.PMID: 28933516 Free PMC article. Updated. Review.
Omalizumab for asthma in adults and children.
Normansell R, Walker S, Milan SJ, Walters EH, Nair P.Cochrane Database Syst Rev. 2014 Jan 13;(1):CD003559. doi: 10.1002/14651858.CD003559.pub4.PMID: 24414989 Review.
KMEL References
References
-
- Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet. 2018;391:350-400.
-
- McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care Med. 2019;199:433-445.
-
- Kuruvilla ME, Lee FE-H, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56:219-233.
-
- Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31:143-178.
-
- GINA. Difficult-to-treat and severe asthma in adolescent and adult patients. Diagnosis and management. A GINA Pocket Guide for Health Professionals. 2018 https://ginasthma.org/wp-content/uploads/2019/04/GINA-Severe-asthma-Pock...
-
- Molfino NA, Gossage D, Kolbeck R, Parker JM, Geba GP. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy. 2012;42:712-737.
-
- FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128-2141.
-
- Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β (2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115-2127.
-
- Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184:1125-1132.
-
- Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3:355-366.
-
- Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380:651-659.
-
- Ortega HG, Yancey SW, Mayer B, et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4:549-556.
-
- Heaney LG, Perez de Llano L, Al-Ahmad M, et al. Eosinophilic and non-eosinophilic asthma: an expert consensus framework to characterize phenotypes in a global real-life severe asthma cohort. Chest. 2021;160:814-830.
-
- Corren J. Inhibition of interleukin-5 for the treatment of eosinophilic diseases. Discov Med. 2012;13:305-312.
-
- Global Initiative for Asthma. Global Strategy for Asthma Managment and Prevention. 2020 https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-...
-
- Kuruvilla M, Ariue B, Oppenheimer JJ, Singh U, Bernstein JA. Clinical use of biologics for asthma treatment by allergy specialists: a questionnaire survey. Ann Allergy Asthma Immunol. 2020;125:433-439. doi:10.1016/j.anai.2020.06.041
-
- Porsbjerg CM, Menzies-Gow AN, Tran TN, et al. Global variability in administrative approval prescription criteria for biologic therapy in severe asthma. J Allergy Clin Immunol Pract. 2022;10:1202-1216.
-
- Albers FC, Müllerová H, Gunsoy NB, et al. Biologic treatment eligibility for real-world patients with severe asthma: the IDEAL study. J Asthma. 2018;55:152-160.
-
- Cockle SM, Stynes G, Gunsoy NB, et al. Comparative effectiveness of mepolizumab and omalizumab in severe asthma: an indirect treatment comparison. Respir Med. 2017;123:140-148.
-
- Chapman KR, Albers FC, Chipps B, et al. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Allergy. 2019;74:1716-1726.
-
- ISAR Study Group. International severe asthma registry (ISAR): Mission statement. Chest. 2020;157:805-814.
-
- FitzGerald JM, Tran TN, Alacqua M, et al. International severe asthma registry (ISAR): protocol for a global registry. BMC Med Res Methodol. 2020;20:212.
-
- Bulathsinhala L, Eleangovan N, Heaney LG, et al. Development of the international severe asthma registry (ISAR): a modified Delphi study. J Allergy Clin Immunol Pract. 2019;7:578-588.e2.
-
- Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2018 https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-rev...
-
- Ivanova JI, Bergman R, Birnbaum HG, Colice GL, Silverman RA, McLaurin K. Effect of asthma exacerbations on health care costs among asthmatic patients with moderate and severe persistent asthma. J Allergy Clin Immunol. 2012;129:1229-1235.
-
- Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018;11:193-204.
-
- Fong WCG, Azim A, Knight D, et al. Real-world omalizumab and mepolizumab treated difficult asthma phenotypes and their clinical outcomes. Clin Exp Allergy. 2021;51:1019-1032.
-
- Jackson DJ, Busby J, Pfeffer PE, et al. Characterisation of patients with severe asthma in the UK severe asthma registry in the biologic era. Thorax. 2021;76:220-227.
-
- Agache I, Akdis C, Akdis M, et al. EAACI biologicals guidelines: recommendations for severe asthma. Allergy. 2021;76:14-44. https://www.eaaci.org/resources-list/resources/4704-eaeaaci-biologicals-...
-
- Brown T, Jones T, Gove K, et al. Randomised controlled trials in severe asthma: selection by phenotype or stereotype. Eur Respir J. 2018;52:1801444.
-
- Kavanagh JE, Hearn AP, Dhariwal J, et al. Real-world effectiveness of Benralizumab in severe eosinophilic asthma. Chest. 2021;159:496-506.
-
- Domingo Ribas C, Carrillo Díaz T, Blanco Aparicio M, Martínez Moragón E, Banas Conejero D, Sánchez Herrero MG. REal worlD effectiveness and safety of mepolizumab in a multicentric Spanish cohort of asthma patients stratified by eosinophils: the REDES study. Drugs. 2021;81:1763-1774.
-
- Wechsler ME, Peters SP, Hill TD, et al. Clinical outcomes and health-care resource use associated with Reslizumab treatment in adults with severe eosinophilic asthma in real-world practice. Chest. 2021;159:1734-1746.
-
- Papaioannou AI, Mplizou M, Porpodis K, et al. Long-term efficacy and safety of omalizumab in patients with allergic asthma: a real-life study. Allergy Asthma Proc. 2021;42:235-242.
-
- Chung Y, Katial R, Mu F, et al. Real-world effectiveness of benralizumab: results from the ZEPHYR 1 study. Ann Allergy Asthma Immunol. 2022;128:669-676.
-
- Chen W, Sadatsafavi M, Chong Boon Wong N, et al. Impact of initiating biologics in patients on long-term OCS or frequent rescue steroids (GLITTER). American Thoracic Society. 2022;205:A2365.
-
- Viswanathan RK, Busse WW. How to compare the efficacy of biologic agents in asthma. Ann Allergy Asthma Immunol. 2020;125:137-149.
-
- Praetorius K, Henriksen DP, Schmid JM, et al. Indirect comparison of efficacy of dupilumab versus mepolizumab and omalizumab for severe type 2 asthma. ERJ Open Res. 2021;7:7. doi:10.1183/23120541.00306-2021
-
- Kotisalmi E, Hakulinen A, Mäkelä M, Toppila-Salmi S, Kauppi P. A comparison of biologicals in the treatment of adults with severe asthma - real-life experiences. Asthma Res Pract. 2020;6:2.
-
- AlShareef S, McDonald CF, Lee J. Clinical and lung function outcomes after anti-IgE or anti-IL5 therapy in severe asthma. J Asthma Allergy. 2022;15:209-217.
-
- Charles D, Shanley J, Temple S-N, Rattu A, Khaleva E, Roberts G. Real-world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: a systematic review and meta-analysis. Clin Exp Allergy. 2022;52:616-627.
-
- Menzies-Gow A, Gurnell M, Heaney LG, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2021;10:47-58. doi:10.1016/S2213-2600(21)00352-0
-
- Menzies-Gow AN, McBrien C, Unni B, et al. Real world biologic use and switch patterns in severe asthma: data from the international severe asthma registry and the US CHRONICLE study. J Asthma Allergy. 2022;15:63-78.
-
- Study of magnitude and precision of response to omalizumab and mepolizumab in adult severe asthma (PREDICTUMAB). https://clinicaltrials.gov/ct2/show/NCT03476109?term=NCT03476109&draw=2&...