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

Publication date: Available online 19 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): 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

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

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 OGC (prednisolone/prednisone, ≥7.5–50mg/day) for ≥4 weeks. Patients received 300mg subcutaneous mepolizumab or placebo every 4 weeks for 52 weeks. Clinical benefit was defined post hoc as: remission at any time (two definitions used); or ≥50% OGC dose reduction during Weeks 48–52; or no EGPA relapses. The two remission definitions were Birmingham Vasculitis Activity Score [BVAS]=0 plus OGC dose ≤4mg/day (remission¹/clinical benefit¹) or ≤7.5mg/day (remission²/clinical benefit²). Clinical benefit was assessed in all patients, and among subgroups with: baseline blood eosinophil counts[BEC] <150cells/μL; baseline OGC >20mg/day; or, weight >85kg.

Results

With mepolizumab versus placebo, 78% versus 32% of patients experienced clinical benefit¹, and 87% versus 53% of patients experienced clinical benefit² (both p<0.001). Significantly more patients experienced clinical benefit¹ with mepolizumab versus placebo in the BEC <150cells/μL subgroup (72% versus 43%, p=0.033) and weight >85kg subgroup (68% versus 23%, p=0.005); in the OGC >20mg/day subgroup results were not significant but favored mepolizumab (60% versus 36%, p=0.395).

Conclusion

When a comprehensive definition of clinical benefit was applied to data from a randomized controlled trial, 78%–87% of patients with EGPA experienced benefit with mepolizumab.

Graphical abstract

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