[en] [en] BACKGROUND: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.
METHODS: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately.
RESULTS: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day-1, 95% CI -5.24-2.62 mg·day-1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.
CONCLUSIONS: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
Disciplines :
General & internal medicine
Author, co-author :
Kroes, Johannes A; Medical Centre Leeuwarden, Leeuwarden, Netherlands
Alfonso-Cristancho, Rafael; GlaxoSmithKline, Collegeville, PA, USA
Bansal, Aruna T; Acclarogen Ltd, St John's Innovation Centre, Cambridge, UK
Berret, Emmanuelle; European Respiratory Society, Lausanne, Switzerland
Bieksiene, Kristina; Lithuanian University of Health Sciences, Kaunas, Lithuania
Bourdin, Arnaud ; University of Montpellier, Montpellier, France
Brussino, Luisa; University of Turin, Turin, Italy
Canhoto, Diogo; University of Coimbra, Coimbra, Portugal
Cardini, Cristina; Severe Asthma Network in Italy, Milan, Italy
Celik, Gulfem; Ankara University School of Medicine, Ankara, Turkey
Csoma, Zsuzsanna; National Koranyi Institute for Pulmonology, Budapest, Hungary
Dahlén, Barbro; Karolinska Institutet, Stockholm, Sweden
Damadoglu, Ebru; Hacettepe University Faculty of Medicine, Ankara, Turkey
Eger, Katrien ; University of Amsterdam, Amsterdam, Netherlands
Gauquelin, Lisa; AP-HP Sorbonne Université, Hôpital Pitié Salpêtrière, Paris, France
Gemicioglu, Bilun ; Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey
Goksel, Ozlem; Ege University, Faculty of Medicine, Izmir, Turkey
Graff, Sophie ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Support statement: This study was supported by GlaxoSmithKline (study identifier: 212821). Funding information for this article has been deposited with the Crossref Funder Registry.
Pavord ID, Bel EH, Bourdin A, et al. From DREAM to REALITI-A and beyond: mepolizumab for the treatment of eosinophil-driven diseases. Allergy 2022; 77: 778–797.
Li J, Wang F, Lin C, et al. The efficacy and safety of reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: a systematic review and meta-analysis. J Asthma 2017; 54: 300–307.
Tian BP, Zhang GS, Lou J, et al. Efficacy and safety of benralizumab for eosinophilic asthma: a systematic review and meta-analysis of randomized controlled trials. J Asthma 2018; 55: 956–965.
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.
Richards LB, van Bragt JJMH, Aarab R, et al. Treatment eligibility of real-life mepolizumab-treated severe asthma patients. J Allergy Clin Immunol Pract 2020; 8: 2999–3008.
Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-world evidence – what is it and what can it tell us? N Engl J Med 2016; 375: 2293–2297.
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.
Paoletti G, Pepys J, Casini M, et al. Biologics in severe asthma: the role of real-world evidence from registries. Eur Respir Rev 2022; 31: 210278.
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.
Bentzen HB, Høstmælingen N. Balancing protection and free movement of personal data: the new European Union general data protection regulation. Ann Intern Med 2019; 170: 335–337.
Wirth FN, Meurers T, Johns M, et al. Privacy-preserving data sharing infrastructures for medical research: systematization and comparison. BMC Med Inform Decis Mak 2021; 21: 242.
Observational Health Data Sciences and Informatics. Standardized Data: the OMOP Common Data Model. 2022. www.ohdsi.org/data-standardization/the-common-data-model/. Date last accessed: 24 January 2022.
Kent S, Burn E, Dawoud D, et al. Common problems, common data model solutions: evidence generation for health technology assessment. Pharmacoeconomics 2021; 39: 275–285.
Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med 2022; 386: 157–171.
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, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371: 1198–1207.
Chupp GL, Bradford ES, Albers FC, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med 2017; 5: 390–400.
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.
Harrison T, Canonica GW, Chupp G, et al. Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis. Eur Respir J 2020; 56: 2000151.
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.
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.
Eger K, Paroczai D, Bacon A, et al. The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good? ERJ Open Res 2022; 8: 00065-2022.
Biedermann P, Ong R, Davydov A, et al. Standardizing registry data to the OMOP common data model: experience from three pulmonary hypertension databases. BMC Med Res Methodol 2021; 21: 238.
Kroes JA, Bansal AT, Berret E, et al. Blueprint for harmonizing unstandardized disease registries to allow federated data analysis: prepare for the future. ERJ Open Res 2022; 8: 00168-2022.
R Core Team. R: A Language and Environment for Statistical Computing. Vienna, R Foundation for Statistical Computing, 2021. www.R-project.org/. Date last accessed: 25 May 2022.
Thomas D, Harvey ES, McDonald VM, et al. Mepolizumab and oral corticosteroid stewardship: data from the Australian Mepolizumab Registry. J Allergy Clin Immunol Pract 2021; 9: 2715–2724.
Silver J, Bogart M, Packnett E, et al. Real-world reductions in oral corticosteroid use in the USA following mepolizumab therapy for severe asthma. J Asthma Allergy 2020; 13: 689–699.
Elsey L, Pantin T, Holmes LJ, et al. Outcomes over the first two years of treatment with mepolizumab in severe asthma. Eur Respir J 2021; 58: 2101313.
Pilette C, Canonica GW, Chaudhuri R, et al. REALITI – a study: real-world oral corticosteroid-sparing effect of mepolizumab in severe asthma. J Allergy Clin Immunol Pract 2022; 10: 2646-2656.
Li H, Zhang Q, Wang J, et al. Real-world effectiveness of mepolizumab in severe eosinophilic asthma: a systematic review and meta-analysis. Clin Ther 2021; 43: e192–e208.
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 2022; 10: 47–58.
Korn S, Howarth P, Smith SG, et al. Development of methodology for assessing steroid-tapering in clinical trials for biologics in asthma. Respir Res 2022; 23: 45.
Eger K, Kroes JA, Ten Brinke A, et al. Long-term therapy response to anti-IL-5 biologics in severe asthma – a real-life evaluation. J Allergy Clin Immunol Pract 2021; 9: 1194–1200.
