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. 2023 Apr 3;9(2):00745-2022.
doi: 10.1183/23120541.00745-2022. eCollection 2023 Mar.

Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis

Johannes A Kroes  1 , Rafael Alfonso-Cristancho  2 , Aruna T Bansal  3 , Emmanuelle Berret  4 , Kristina Bieksiene  5 , Arnaud Bourdin  6 , Luisa Brussino  7 , Diogo Canhoto  8 , Cristina Cardini  9 , Gulfem Celik  10 , Zsuzsanna Csoma  11 , Barbro Dahlén  12 , Ebru Damadoglu  13 , Katrien Eger  14 , Lisa Gauquelin  15 , Bilun Gemicioglu  16 , Ozlem Goksel  17 , Sophie Graff  18 , Enrico Heffler  19   20 , Hendrik B Hofstee  21 , Peter Howarth  22 , Rupert W Jakes  22 , Fabienne Jaun  23 , Virginija Kalinauskaite-Zukauske  5 , Peter Kopač  24   25 , Namhee Kwon  22 , Claudia C Loureiro  26 , Victor Lozoya García  27 , Matthew Masoli  28 , Mariana Paula Rezelj  24 , Luis Pérez De Llano  29 , Sanja Popović-Grle  30 , David Ramos-Barbón  31 , Ana Sà Sousa  32 , Konstantinos Samitas  33 , Florence Schleich  18   34 , Concetta Sirena  9 , Sabina Skrgat  25   35 , Eleftherios Zervas  33 , George Zichnalis  36 , Elisabeth H Bel  14 , Jacob K Sont  21 , Simone Hashimoto  14 , Anneke Ten Brinke  1
Affiliations

Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis

Johannes A Kroes et al. ERJ Open Res. .

Abstract

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.

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Conflict of interest statement

Conflict of interest: Z. Csoma reports lecture honoraria from AstraZenca, Sanofi, Teva and GSK outside the submitted work. A. ten Brinke reports grants and payment for expert testimony from GlaxoSmithKline, AstraZeneca, TEVA and Sanofi-Genzyme Regeneron outside the submitted work. B. Gemicioglu reports support for the present work from GSK; lecture honoraria from GSK, Novartis, Deva, Chiesi, Abdi İbrahim and Sandoz; travel support from GSK, AstraZeneca and Novartis; and leadership positions with SHARP (Turkey Coordinator), GARD (Turkey Coordinator) and Turkish Board of Pulmonology (Chair), outside the submitted work. C.C. Loureiro reports grants from GSK; consulting fees from AstraZeneca, GSK, Novartis and Sanofi; lecture honoraria from AstraZeneca, GSK, Novartis, Sanofi and Teva; and travel support from AstraZeneca, Novartis and Sanofi, outside the submitted work. D. Ramos-Barbón reports honoraria and institutional research funding from GSK, outside the submitted work. E.H. Bel reports grants from GlaxoSmithKline and TEVA; lecture honoraria from GlaxoSmithKline, TEVA, AstraZeneca, Sanofi-Genzyme, Regeneron, Chiesi and Sterna, outside the submitted work. J.A. Kroes reports grants from AstraZeneca, outside the submitted work. K. Samitas reports lecture honoraria from MSD, GSK, Chiesi, Novartis, AstraZeneca, ELPEN, Menarini, BMS, Specialty Therapeutics, Boehringer and Rontis; travel support from Boehringer; advisory board participation with AstraZeneca, GSK and Specialty Therapeutics; and a leadership position with the Hellenic Thoracic Society, outside the submitted work. L. Pérez de Llano reports support for the present work from AstraZeneca; grants from AstraZeneca, Faes, TEVA and Sanofi; lecture honoraria from AstraZeneca, TEVA, Sanofi, MSD, Leo Pharma, Gebro, GSK, Novartis, Chiesi, Techdow Pharma and Gilead; patents from AstraZeneca, Novartis, Faes, TEVA, GSK, Sanofi and Chiesi; and advisory board participation with AstraZeneca, outside the submitted work. R.W. Jakes reports support for the present work from GSK, as an employee and shareholder. S. Škrgat reports honoraria for lectures and educational events, supported by AstraZeneca, Sanofi, Chiesi, Pliva Teva and Medis; and participation on advisory boards of AstraZeneca, Chiesi and Sanofi, outside the submitted work. A. Bourdin reports support for the present work from GSK; grants from AstraZeneca, GSK and Boehringer Ingelheim; lecture honoraria, nonfinancial support and other support from AstraZeneca, GSK, Boehringer Ingelheim, Novartis, TEVA, Chiesi Farmaceuticals, Actelion, Gilead, Roche and Regeneron, outside the submitted work. B. Dahlén reports grants from Novartis and GSK; and consulting fees from AstraZeneca, Teva and Sanofi, outside the submitted work. E. Zervas reports advisory board fees from Astra, Chiesi, Elpen, GSK, Menarini, MSD and Novartis; honoraria and fees for lectures from Astra, Boehringer, Bristol-Myers, Chiesi, Elpen, GSK, Menarini, MSD and Novartis; travel accommodations and meeting expenses from Astra, Boehringer, Chiezi, Galenica, GSK, Elpen, MSD, Novartis and Roche; and holds a leadership role as Secretary General of Hellenic Thoracic Society, outside the submitted work. E. Heffler reports consulting fees and lecture honoraria from AstraZeneca, Sanofi, Regeneron, Novartis, GSK, Stallergenes-Greer and Circassia outside the submitted work. F. Schleich reports grants from GSK and AstraZeneca; and consulting fees and lecture honoraria from GSK, AstraZeneca and Chiesi, outside the submitted work. K. Eger reports that TEVA sponsored printing their PhD thesis, outside the submitted work. K. Bieksiene reports lecture honoraria from AstraZeneca and Berlin Chemie, outside the submitted work. M. Paula Rezelj reports lecture honoraria from AstraZeneca, Novartis, GSK and Stallergenes, outside the submitted work. M. Masoli reports an investigator-led nonpromotional grant from GlakoSmithKline and an advisory board fee from AstraZeneca outside the submitted work. N. Kwon reports support for the present work from GSK, as an employee and shareholder. P. Howarth reports support for the present work from GSK, as an employee and shareholder. P. Kopač reports lecture honoraria and advisory board participation from AstraZeneca, GSK and Berlin-Chemie outside the submitted work. R. Alfonso-Cristancho reports support for the present work from GSK, as an employee and shareholder. G. Celik reports consulting fees and lecture honoraria from Novartis and GSK outside the submitted work. J.K. Sont reports grants from AstraZeneca; outside the submitted work. All other authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Flow chart of selected patients. Data are presented as n or n (%). SHARP: Severe Heterogeneous Asthma Registry, Patient-centred; BE: Belgium; ES: Spain; FR: France; HR: Croatia; IT: Italy; LT: Lithuania; NL: the Netherlands; PT: Portugal; SI: Slovenia; TR: Turkey.
FIGURE 2
FIGURE 2
Forest plot of the odds of having experienced two or more exacerbations per year after mepolizumab initiation compared to the year before initiating mepolizumab for the individual countries and the countries combined. The odds were statistically significantly reduced for both the pre-pandemic group (n=369) and the pandemic group (n=194).
FIGURE 3
FIGURE 3
Forest plot of the odds of receiving maintenance oral corticosteroid treatment after mepolizumab initiation for the individual countries and the countries combined. The odds were statistically significantly reduced from baseline for the pre-pandemic group (n=449), but not for the pandemic group (n=138).
FIGURE 4
FIGURE 4
Forest plot of the reduction in mean maintenance oral corticosteroid dose after mepolizumab initiation. for the individual countries and the countries combined. The dose was statistically significantly reduced from baseline for the pre-pandemic group (n=161), but not for the pandemic group (n=34).
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