Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis

Jonathan Steinfeld, Eric S. Bradford, Judith Brown, Stephen Mallett, Steven W. Yancey, Praveen Akuthota, Maria C. Cid, Gerald J. Gleich, David Jayne, Paneez Khoury, Carol A. Langford, Peter A. Merkel, Frank Moosig, Ulrich Specks, Peter F. Weller, Michael E. Wechsler

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: In a recent phase III trial (NCT02020889) 53% of mepolizumab-treated versus 19% of placebo-treated patients with eosinophilic granulomatosis with polyangiitis (EGPA) achieved protocol-defined remission. Objective: We sought to investigate post hoc the clinical benefit of mepolizumab in patients with EGPA using a comprehensive definition of benefit encompassing remission, oral glucocorticoid (OGC) dose reduction, and EGPA relapses. Methods: The randomized, placebo-controlled, double-blind, parallel-group trial recruited patients with relapsing/refractory EGPA receiving stable OGCs (prednisolone/prednisone, ≥7.5–50 mg/d) for 4 or more weeks. Patients received 300 mg of subcutaneous mepolizumab or placebo every 4 weeks for 52 weeks. Clinical benefit was defined post hoc as follows: remission at any time (2 definitions used), 50% or greater OGC dose reduction during weeks 48 to 52, or no EGPA relapses. The 2 remission definitions were Birmingham Vasculitis Activity Score of 0 plus OGC dose of 4 mg/d or less (remission 1/clinical benefit 1) or 7.5 mg/d or less (remission 2/clinical benefit 2). Clinical benefit was assessed in all patients and among subgroups with a baseline blood eosinophil count of less than 150 cells/μL, baseline OGC dosage of greater than 20 mg/d, or weight of greater than 85 kg. Results: With mepolizumab versus placebo, 78% versus 32% of patients experienced clinical benefit 1, and 87% versus 53% of patients experienced clinical benefit 2 (both P < .001). Significantly more patients experienced clinical benefit 1 with mepolizumab versus placebo in the blood eosinophil count less than 150 cells/μL subgroup (72% vs 43%, P = .033) and weight greater than 85 kg subgroup (68% vs 23%, P = .005); in the OGC greater than 20 mg/d subgroup, results were not significant but favored mepolizumab (60% vs 36%, P = .395). Conclusion: When a comprehensive definition of clinical benefit was applied to data from a randomized controlled trial, 78% to 87% of patients with EGPA experienced benefit with mepolizumab.

Original languageEnglish (US)
Pages (from-to)2170-2177
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume143
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Churg-Strauss syndrome
  • Eosinophilic granulomatosis with polyangiitis
  • IL-5
  • eosinophils
  • mepolizumab
  • vasculitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Steinfeld, J., Bradford, E. S., Brown, J., Mallett, S., Yancey, S. W., Akuthota, P., Cid, M. C., Gleich, G. J., Jayne, D., Khoury, P., Langford, C. A., Merkel, P. A., Moosig, F., Specks, U., Weller, P. F., & Wechsler, M. E. (2019). Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. Journal of Allergy and Clinical Immunology, 143(6), 2170-2177. https://doi.org/10.1016/j.jaci.2018.11.041