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

David R W Jayne; Benjamin Terrier; Bernhard Hellmich; Paneez Khoury; Lee Baylis; Jane H Bentley; Jonathan Steinfeld; Steven W Yancey; Namhee Kwon; Michael E Wechsler; Praveen Akuthota

doi:10.1183/23120541.00509-2023

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

ERJ Open Res. 2024 Jan 8;10(1):00509-2023. doi: 10.1183/23120541.00509-2023. eCollection 2024 Jan.

Authors

Affiliations

¹ Department of Medicine, University of Cambridge, Cambridge, UK.
² Service de Médecine Interne, Hôpital Cochin, Paris, France.
³ Klinik für Innere Medizin, Rheumatologie und Immunologie, Medius Kliniken, Universität Tübingen, Kirchheim-Teck, Germany.
⁴ Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Global Medical Affairs, GSK, Durham, NC, USA.
⁶ Clinical Statistics, GSK, Brentford, UK.
⁷ Respiratory Therapy Area Unit and Flexible Discovery Unit, GSK, Philadelphia, PA, USA.
⁸ Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA.
⁹ Clinical Sciences, Respiratory, GSK, Brentford, Middlesex, UK.
¹⁰ Department of Medicine, National Jewish Health, Denver, CO, USA.
¹¹ Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, La Jolla, CA, USA.

Abstract

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.

Grants and funding

U01 AI097073/AI/NIAID NIH HHS/United States