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 non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.
Aim To harmonize data from 10 national severe asthma registries and characterize 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 harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.
Results In 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) 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 harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold 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.
Footnotes
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Conflict of interest: Zsuzsanna Csoma reports lecture honoraria from AstraZenca, Sanofi, Teva, GSK; outside the submitted work.
Conflict of interest: Anneke ten Brinke reports grants and payment for expert testimony from GlaxoSmithKline, AstraZeneca, TEVA, Sanofi-Genzyme Regeneron; outside the submitted work.
Conflict of interest: Bilun Gemicioglu reports support for the present work from GSK; lecture honoraria from GSK, Novartis, Deva, Chiesi, Abdi İbrahim, Sandoz; travel support from GSK, Astrazeneca, Novartis; leadership positions with SHARP (Turkey Coordinator), GARD (Turkey Coordinator), Turkish Board of Pulmonology (Chair); outside the submitted work.
Conflict of interest: Cláudia Chaves Loureiro reports grants from GSK; consulting fees from AstraZeneca, GSK, Novartis, Sanofi; lecture honoraria from AstraZeneca, GSK, Novartis, Sanofi, Teva; travel support from AstraZeneca, Novartis, Sanofi; outside the submitted work.
Conflict of interest: David Ramos Barbón reports honoraria and institutional research funding from GSK, outside the submitted work.
Conflict of interest: Elisabeth HD Bel reports grants from GlaxoSmithKline, TEVA; lecture honoraria from GlaxoSmithKline, TEVA, AstraZeneca, Sanofi-Genzyme, Regeneron, Chiesi, Sterna; outside the submitted work.
Conflict of interest: Johannes A Kroes reports grants from AstraZeneca, outside the submitted work.
Conflict of interest: Konstantinos Samitas reports lecture honoraria from MSD, GSK, Chiesi, Novartis, AstraZeneca, ELPEN, Menarini, BMS, Specialty Therapeutics, Boehringer, Rontis; travel support from Boehringer; advisory board participation with AstraZeneca, GSK, Specialty Therapeutics; and a leadership position with the Hellenic Thoracic Society; outside the submitted work.
Conflict of interest: Luis Pérez de Llano report support for the present work from AstraZeneca; grants from AstraZeneca, Faes, TEVA, Sanofi; lecture honoraria from AstraZeneca, TEVA, Sanofi, MSD, Leo Pharma, Gebro, GSK, Novartis, Chiesi, Techdow Pharma, Gilead; patents from AstraZeneca, Novartis, Faes, TEVA, GSK, Sanofi, Chiesi; advisory board participation with AstraZeneca; outside the submitted work.
Conflict of interest: Rupert Jakes reports support for the present work from GSK, as an employee and shareholder.
Conflict of interest: Sabina Škrgat reports honoraria for lectures and educational events, supported by Astra Zeneca, Sanofi, Chiesi, Pliva Teva and Medis; participation on Advisory boards of Astra Zeneca, Chiesi, Sanofi; outside the submitted work.
Conflict of interest: Arnaud Bourdin reports support for the present work from GSK; grants from AstraZeneca, GSK, Boehringer Ingelheim; lecture honoraria, non-financial support and other support from AstraZeneca, GSK, Boehringer Ingelheim, Novartis, TEVA, Chiesi Farmaceuticals, Actelion, Gilead, Roche, Regeneron; outside the submitted work.
Conflict of interest: Barbro Dahlén reports grants from Novartis, GSK; consulting fees from AstraZeneca, Teva, Sanofi; outside the submitted work.
Conflict of interest: Eleftherios Zervas reports advisory board fees from Astra, Chiesi, Elpen, GSK, Menarini, MSD, Novartis; honoraria and fees for lectures from Astra, Boehringer, Bristol-Myers, Chiesi, Elpen, GSK, Menarini, MSD, Novartis; travel accommodations and meeting expenses from Astra, Boehringer, Chiezi, Galenica, GSK, Elpen, MSD, Novartis, Roche; and holds a leadership role as Secretary General of Hellenic Thoracic Society; outside the submitted work.
Conflict of interest: Enrico Heffler reports consulting fees and lecture honoraria from AstraZenca, Sanofi, Regeneron, Novartis, GSK, Stallergenes-Greer, Circassia; outside the submitted work.
Conflict of interest: Florence Schleich reports grants from GSK, Astrazeneca; consulting fees and lecture honoraria from GSK, Astrazeneca, Chiesi; outside the submitted work.
Conflict of interest: Katrien Eger reports that TEVA sponsored printing their PhD thesis; outside the submitted work.
Conflict of interest: Kristina Bieksiene reports lecture honoraria from Astra Zeneca, Berlin Chemy; outside the submitted work.
Conflict of interest: Mariana Paula Rezelj reports lecture honoraria from AstraZenca, Novartis, GSK, Stallergenes; outside the submitted work.
Conflict of interest: Matthew Masoli reports an investigator led non promotional grant from GlakoSmithKline; Advisory board fee from Astra Zeneca; outside the submitted work.
Conflict of interest: Namhee Kwon reports support for the present work from GSK, as an employee and shareholder.
Conflict of interest: Peter Howarth reports support for the present work from GSK, as an employee and shareholder.
Conflict of interest: Peter Kopač reports lecture honoraria and advisory board participation from Astra Zeneca, GSK, Berlin-Chemie; outside the submitted work.
Conflict of interest: Rafael Alfonso-Cristancho reports support for the present work from GSK, as an employee and shareholder.
Conflict of interest: Gülfem Celik reports consulting fees and lecture honoraria from Novartis, GSK; outside the submitted work.
Conflict of interest: J.K. Sont reports grants from AstraZeneca; outside the submitted work.
Conflict of interest: All other authors have nothing to disclose.
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- Received January 3, 2023.
- Accepted January 3, 2023.
- Copyright ©The authors 2023
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