Abstract
Background The MIRRA trial (GSK ID: 115921/NCT02020889) demonstrated that mepolizumab increased remission time and reduced oral corticosteroid (OCS) use compared with placebo in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). The present analysis investigated the impact of baseline characteristics on clinical outcomes and characterised the OCS-sparing effect of mepolizumab.
Methods In a Phase III, randomised controlled trial for patients with EGPA (MIRRA), patients received standard of care plus mepolizumab 300 mg or placebo every 4 weeks for 52 weeks. The accrued duration of remission, the proportion of patients in remission at Weeks 36 and 48, and the proportion of patients with clinical benefit (remission, OCS, or relapse-related) were assessed according to baseline EGPA characteristic subgroups (post hoc). Mepolizumab-related OCS-sparing benefits were also quantified.
Results Accrued duration of remission and the proportion of patients in remission at Weeks 36 and 48 were greater with mepolizumab than placebo across baseline subgroups: refractory disease, immunosuppressant use, EGPA duration, relapse number, and OCS use ≤20 mg·day−1. The proportion of patients with clinical benefit was greater with mepolizumab versus placebo (range: 76–81% versus 25–39%), irrespective of immunosuppressant use or EGPA duration. Patients treated with mepolizumab versus placebo accrued significantly more weeks on OCS ≤4 mg·day−1 (odds ratio [95% confidence interval]: 5.06 [2.47,10.38]) and had a mean of 1423.1 mg less per-patient OCS exposure over 52 weeks.
Conclusions Mepolizumab treatment provided benefits to patients with EGPA across varying baseline clinical characteristics and can be considered an OCS-sparing treatment in EGPA.
Footnotes
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Conflicts of interest: DRWJ has received research grants, consultancy fees from AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Chemocentryx, GSK, Janssen, Novartis, Roche/Genentech, Takeda, and Vifor, speaker fees from Amgn, Vifor and GSK, and was supported by the NIHR Cambridge Biomedical Research Centre.
Conflicts of interest: BT reports consulting fees from AstraZeneca, Vifor, and GSK; Payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from AstraZeneca, Vifor, GSK, and Boehringer Ingelheim and support for attending meetings and/or travel from Vifor and GSK.
Conflicts of interest: BH reports personal fees for lectures or advisory services from Amgen, AstraZeneca, BMS, Boehringer Ingelheim Chugai, InflaRx, GSK, Pfizer, Phadia, MSD, Roche, Novartis and Vifor, outside the submitted work.
Conflicts of interest: PK received research funding from the American Partnership for Eosinophilic Disorders.
Conflicts of interest: MEW has research grants with the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute and is a consultant with GSK, Genentech, Sanofi, Regeneron, AstraZeneca, Teva, Novartis, Boehringer Ingelheim, Sentien, and Equillium.
Conflicts of interest: PA has research grants with the National Heart, Lung and Blood Institute, and the American Partnership for Eosinophilic Disorders, and declares himself as a paid instructor for AstraZeneca; consultant for AstraZeneca, GSK, Sanofi, and has received grant/research support from GSK, AstraZeneca and Regeneron.
Conflicts of interest: LB and JHB, are employees of GSK and own stocks/shares in GSK.
Conflicts of interest: JS, SWY, and NK were employees of GSK at the time of this study and own stocks/shares in GSK.
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- Received July 19, 2023.
- Accepted October 6, 2023.
- Copyright ©The authors 2023
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