[en] ("[en] INTRODUCTION: Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown.
MATERIALS AND METHODS: The European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies.
RESULTS: Availability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity.
CONCLUSION: Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation.","[en] ","")
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Frix, Anne-Noëlle ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Heaney, Liam G; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK
Dahlén, Barbro; Respiratory Medicine Unit, Department of Medicine, Solna Campus, and Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
Mihaltan, Florin; National Institute of Pneumology M. Nasta, Bucharest, Romania
Sergejeva, Svetlana; Institute of Technology, University of Tartu, Tartu, Estonia
Popović-Grle, Sanja; The Clinic for Lung Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia
Sedlak, Vratislav; Department of Pneumology, University Hospital and Charles University Faculty of Medicine, Hradec Kralove, Czech Republic
Lehtimäki, Lauri ; Allergy Centre, Tampere University Hospital, and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Zervas, Eleftherios ; Respiratory Medicine Department and Asthma Center, Athens Chest Hospital "Sotiria", Athens, Greece
Csoma, Zsuzsanna; National Korányi Institute of Pulmonology, Budapest, Hungary
Lúðvíksdóttir, Dora; Department of Allergy, Respiratory Medicine and Sleep Landspitali University Hospital Reykjavik Iceland, University of Iceland, Reykjavik, Iceland
Butler, Marcus ; St Vincent's University Hospital, University College Dublin, Dublin, Ireland ; School of Medicine, University College Dublin, Dublin, Ireland
Canonica, Giorgio Walter ; Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy
Grisle, Ineta; Latvian Association of Allergists Center of Tuberculosis and Lung Diseases, Riga, Latvia
Bieksiene, Kristina; Department of Pulmonology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Ten Brinke, Anneke; Department of Respiratory Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands
Kuna, Piotr; Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital Medical University of Lodz, Lodz, Poland
Chaves Loureiro, Claudia; Pulmonology Department, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Nenasheva, Natalia M; Department of Allergology and Immunology, Russian Medical Academy of Continuous Professional Education, Moscow, Russia
Lazic, Zorica; Faculty of Medical Sciences, University of Kragujevac, and Clinic for Pulmonology, Clinical Centre, Kragujevac, Serbia
Škrgat, Sabina; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
Ramos-Barbon, David; Respiratory Research Unit, Complexo Hospitalario Universitario & Instituto de Investigación Biomédica de A Coruña (INIBIC), Spain
Leuppi, Joerg; University Clinic of Medicine, Cantonal Hospital Basel, Liestal, Switzerland ; University of Basel, Basel, Switzerland
Gemicioglu, Bilun; Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey
Bossios, Apostolos ; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
Porsbjerg, Celeste M; Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark
Bel, Elisabeth H; Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Djukanovic, Ratko; Faculty of Medicine, University of Southampton, Southampton, UK ; NIHR Southampton Biomedical Research Centre, Southampton, UK
Louis, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Novartis Chiesi Farmaceutici Spa Sanofi ERS - European Respiratory Society GSK - GlaxoSmithKline
Funding text :
The SHARP National Leads survey revealed that corticosteroid-induced toxicity was assessed in 20 countries (mainly by clinical evaluation and cortisol blood levels). This was supported by data extracted from the Experts Broad Survey, which showed evaluation by 70% of experts. Cortisol blood level and clinical evaluation were also the most commonly used assessment modalities.Support statement: The SHARP CRC has been supported by financial and other contributions from the following consortium partners: European Respiratory Society, GlaxoSmithKline Research and Development Limited, Chiesi Farmaceutici SPA, Novartis Pharma AG, Sanofi-Genzyme Corporation, and Teva Branded Pharmaceutical Products R&D, Inc. Funding information for this article has been deposited with the Crossref Funder Registry.
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2021. Available from: http://ginasthma.org/
Hekking PPW, Wener RR, Amelink M, et al. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015; 135: 896–902.
Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43: 343–373.
Israel E, Reddel HK. Severe and difficult-to-treat asthma in adults. N Engl J Med 2017; 377: 965–976.
Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet 2018; 391: 350–400.
Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med 2022; 386: 157–171.
Djukanovic R, Adcock IM, Anderson G, et al. The severe heterogeneous asthma research collaboration, patient-centred (SHARP) ERS clinical research collaboration: a new dawn in asthma research. Eur Respir J 2018; 52: 1801671.
van Bragt JJMH, Adcock IM, Bel EHD, et al. Characteristics and treatment regimens across ERS SHARP severe asthma registries. Eur Respir J 2020; 55: 1901163.
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.e23.
Calzetta L, Matera MG, Rogliani P. Monoclonal antibodies in severe asthma: is it worth it? Expert Opin Drug Metab Toxicol 2019; 15: 517–520.
Canonica GW, Harrison TW, Chanez P, et al. Benralizumab improves symptoms of patients with severe, eosinophilic asthma with a diagnosis of nasal polyposis. Allergy 2022; 77: 150–161.
Menzella F, Fontana M, Contoli M, et al. Efficacy and safety of omalizumab treatment over a 16-year follow-up: when a clinical trial meets real-life. J Asthma Allergy 2022; 15: 505–515.
Graff S, Brusselle G, Hanon S, et al. Anti-interleukin-5 therapy is associated with attenuated lung function decline in severe eosinophilic asthma patients from the Belgian severe asthma registry. J Allergy Clin Immunol Pract 2022; 10: 467–477.
Wechsler ME, Ford LB, Maspero JF, et al. Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): an open-label extension study. Lancet Respir Med 2022; 10: 11–25.
Hansen S, Ulrik C, Hilberg O, et al. The effectiveness of anti-IL5 biologics is comparable in previous-smokers and never-smokers with severe asthma. Eur Respir J 2021; 58: Suppl. 65, PA3742.
Buhl R, Humbert M, Bjermer L, et al. Severe eosinophilic asthma: a roadmap to consensus. Eur Respir J 2017; 49: 1700634.
Frix AN, Schleich F, Paulus V, et al. Effectiveness of omalizumab on patient reported outcomes, lung function, and inflammatory markers in severe allergic asthma. Biochem Pharmacol 2020; 179: 113944.
Schleich F, Graff S, Nekoee H, et al. Real-world experience with mepolizumab: does it deliver what it has promised? Clin Exp Allergy 2020; 50: 687–695.
Upham JW, Le Lievre C, Jackson DJ, et al. Defining a severe asthma super-responder: findings from a Delphi process. J Allergy Clin Immunol Pract 2021; 9: 3997–4004.
Pelaia C, Crimi C, Nolasco S, et al. Switch from omalizumab to benralizumab in allergic patients with severe eosinophilic asthma: a real-life experience from southern Italy. Biomedicines 2021; 9: 1822.
Carpagnano GE, Pelaia C, D’Amato M, et al. Switching from omalizumab to mepolizumab: real-life experience from Southern Italy. Ther Adv Respir Dis 2020; 14: 175346662092923.
Numata T, Araya J, Miyagawa H, et al. Effectiveness of switching biologics for severe asthma patients in Japan: a single-center retrospective study. J Asthma Allergy 2021; 14: 609–618.
Ortega G, Tongchinsub P, Carr T. Combination biologic therapy for severe persistent asthma. Ann Allergy Asthma Immunol 2019; 123: 309–311.
Dedaj R, Unsel L. Case study: a combination of Mepolizumab and Omaluzimab injections for severe asthma. J Asthma 2019; 56: 473–474.
Wechsler ME, Ruddy MK, Pavord ID, et al. Efficacy and safety of Itepekimab in patients with moderate-to-severe asthma. N Engl J Med 2021; 385: 1656–1668.
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.
Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of Mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371: 1189–1197.
Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med 2017; 376: 2448–2458.
Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med 2018; 378: 2475–2485.
McDowell PJ, Stone JH, Zhang Y, et al. Quantification of glucocorticoid-associated morbidity in severe asthma using the glucocorticoid toxicity index. J Allergy Clin Immunol Pract 2021; 9: 365–372.
European Medicines Agency. XOLAIR (omalizumab). www.ema.europa.eu/en/medicines/human/EPAR/xolair
Food and Drug Administration. XOLAIR (omalizumab) for injection, for subcutaneous use. www.accessdata. fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf
European Medicines Agency. NUCALA (mepolizumab). www.ema.europa.eu/en/medicines/human/EPAR/nucala
Food and Drug Administration. NUCALA (mepolizumab) for injection, for subcutaneous use. www.accessdata. fda.gov/drugsatfda_docs/label/2015/125526Orig1s000Lbl.pdf
European Medicines Agency. CINQAERO (reslizumab). www.ema.europa.eu/en/documents/overview/ cinqaero-epar-summary-public_en.pdf
Food and Drug Administration. CINQAIR (reslizumab) injection, for intravenous use. www.accessdata.fda.gov/ drugsatfda_docs/label/2016/761033lbl.pdf
European Medicines Agency. FASENRA (benralizumab). An overview of Fasenra and why it is authorized in the EU. www.ema.europa.eu/en/documents/overview/fasenra-epar-medicine-overview_en.pdf
Food and Drug Administration. FASENRA (benralizumab) injection, for subcutaneous use. www.accessdata. fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf
Food and Drug Administration. DUPIXENT (dupilumab) injection, for subcutaneous use. www.accessdata.fda. gov/drugsatfda_docs/label/2018/761055s007lbl.pdf
European Medicines Agency. DUPIXENT (dupilumab). www.ema.europa.eu/en/documents/product-information/ dupixent-epar-product-information_en.pdf
