Mepolizumab has clinical benefits including oral corticosteroid sparing irrespective of baseline EGPA characteristics.

Background: The Mepolizumab in Relapsing or Refractory EGPA (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 3, 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 the baseline subgroups of 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 (OR 5.06, 95% CI 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.
Competing Interests: Conflict of interest: D.R.W. Jayne has received research grants and consultancy fees from AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Chemocentryx, GSK, Janssen, Novartis, Roche/Genentech, Takeda and Vifor; speaker fees from Amgen, Vifor and GSK; and was supported by the National Institute for Health and Care Research Cambridge Biomedical Research Centre. Conflict of interest: B. Terrier 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. Conflict of interest: B. Hellmich 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. Conflict of interest: P. Khoury received research funding from the American Partnership for Eosinophilic Disorders. Conflict of interest: J.H. Bentley is an employee of GSK and owns stocks/shares in GSK. Conflict of interest: L. Baylis, J. Steinfeld, S.W. Yancey and N. Kwon were employees of GSK at the time of this study and own stocks/shares in GSK. Conflict of interest: M.E. Wechsler 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. Conflict of interest: P. Akuthota 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, and consultant for AstraZeneca, GSK, Sanofi; and has received grant/research support from GSK, AstraZeneca and Regeneron.
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