Two-year efficacy and safety of anti-interleukin-5/receptor therapy for eosinophilic granulomatosis with polyangiitis
- PMID: 40781045
- DOI: 10.1016/j.ard.2025.06.2131
Two-year efficacy and safety of anti-interleukin-5/receptor therapy for eosinophilic granulomatosis with polyangiitis
Abstract
Objectives: To summarise the efficacy and safety of 2 years of anti-interleukin-5/receptor (anti-IL-5/R) therapy in patients with eosinophilic granulomatosis with polyangiitis (EGPA).
Methods: Patients were randomised 1:1 to receive benralizumab or mepolizumab every 4 weeks during the 52-week double-blind period of the MANDARA trial. Patients entered an open-label extension (OLE) in which they continued benralizumab (benralizumab/benralizumab) or switched from mepolizumab to benralizumab (mepolizumab/benralizumab). Remission (Birmingham Vasculitis Activity Score = 0 and oral glucocorticoid [OGC] dose ≤4 mg/d), OGC use, relapse, blood eosinophil count (bEOS), and safety up to year 2 (week 104) were reported.
Results: A total of 128 patients entered the OLE period (n = 66 benralizumab/benralizumab; n = 62 mepolizumab/benralizumab). At week 104, 41 (62.1%) benralizumab/benralizumab patients and 42 (67.7%) mepolizumab/benralizumab patients were in remission. During OLE year 1, 51 (77.3%) benralizumab/benralizumab patients and 42 (67.7%) mepolizumab/benralizumab patients had no relapses. By weeks 49 to 52, 27 (40.9%) benralizumab/benralizumab patients and 16 (25.8%) mepolizumab/benralizumab patients had withdrawn from OGCs, increasing to 29 (43.9%) and 27 (43.5%) at weeks 101 to 104, respectively; the median cumulative OGC dose was 950 mg and 791 mg during OLE year 1, respectively. The median bEOS among benralizumab/benralizumab-treated patients was 20 cells/µL (at weeks 52 and 100), and in mepolizumab/benralizumab-treated patients, it decreased from 70 cells/µL to 20 cells/µL 4 weeks after switching. Adverse events/serious adverse events were reported in 97.0%/22.7% of benralizumab/benralizumab and 100%/35.5% of mepolizumab/benralizumab patients.
Conclusions: In patients with EGPA, treatment for 2 years with anti-IL-5/R therapies is associated with durable rates of remission, discontinuation of OGCs, bEOS depletion, and low relapse rates. Switching from mepolizumab to benralizumab enhances bEOS depletion and OGC sparing.
Copyright © 2025. Published by Elsevier B.V.
Conflict of interest statement
Competing interests PAM reports receiving consulting fees from AbbVie, Alpine Pharmaceuticals, Amgen, Argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, GSK, iCell, Interius BioTherapeutics, Kinevant Sciences, Kyverna, Metagenomi, Neutrolis, Novartis, NS Pharma, Q32 Bio, Quell Therapeutics, Regeneron Pharmaceuticals, Sanofi, Sparrow Pharmaceuticals, Takeda Pharmaceuticals, and Visterra; research support from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eicos, Electra, GSK, Neutrolis, and Takeda; stock options from Kyverna, Q32, Lifordi, and Sparrow Pharmaceuticals; and royalties from UpToDate. PKN reports that his institution received grant support from AstraZeneca, Cyclomedica, Equillium, Foresee, Genentech, Sanofi, and Teva; he has also received honoraria from Arrowhead Pharmaceuticals, AstraZeneca, CSL Behring, GSK, and Sanofi. NK reports receiving consulting fees and research support from AbbVie, Bristol Myers Squibb, and Sanofi; consulting fees only from GSK, Mallinckrodt Pharmaceuticals, Otsuka Pharmaceuticals, and Roche. BT reports receiving consulting fees from AstraZeneca, GSK, Novartis, and Vifor Pharma. BH received speaker fees and/or consultancies from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, GSK, InflaRx, Janssen, MSD, Novartis, Pfizer, Phadia, Roche, and CSL Vifor. AB reports receiving consultancy fees and speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Sanofi Regeneron, and research grants from AstraZeneca, Boehringer Ingelheim, and GSK. DRWJ reports receiving speaker fees and/or consultancies from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, ChemoCentryx, Chugai, GSK, Novartis, Roche, Takeda, and Vifor Pharma; advisory board member for Aurinia, Chinook, GSK, and Takeda. DJJ reports consultancy fees and speakers’ fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, and Sanofi Regeneron, and research grants from AstraZeneca. FR reports receiving consulting fees from AstraZeneca, GSK, and Merck; royalties from UpToDate; and grant support from the FWO/F.R.S.-FNRS (EOS G0H1222N). CP reports receiving consulting and speaker fees from GSK, Otsuka, Pfizer, and Roche; grants and personal speakers or advisory board fees from Roche; served on advisory boards from AstraZeneca, GSK, and Otsuka; and received educational grants from GSK, Otsuka, and Pfizer. US reports receiving consulting fees from Amgen, Argenx, AstraZeneca, Boehringer Ingelheim, and CSL Vifor, and research grants from Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, GSK, NorthStar Medical Radioisotopes, NS Pharma, and Novartis. LBS, CNH, MJ, CM, SN, ER-S, AS, and CW are or were employees of, and may own stock in, AstraZeneca. CM is currently an employee of Amgen. AS is currently an employee of Boehringer Ingelheim. MEW reports receiving consulting, advisory, or speaking honoraria from the following: Allakos, Amgen, Areteia Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Avalo Therapeutics, Celldex, Connect Biopharma, Eli Lilly, Equillium, GSK, Incyte, Kinaset, Kymera, Merck, Phylaxis, Pulmatrix, Rapt Therapeutics, Recludix Pharma, Regeneron Pharmaceuticals, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Tetherex Pharmaceuticals, Uniquity Bio, Upstream Bio, Verona Pharma, and Zurabio.
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