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

Author information

Steinfeld J1, Bradford ES2, Brown J3, Mallett S4, Yancey SW2, Akuthota P5, Cid MC6, Gleich GJ7, Jayne D8, Khoury P9, Langford CA10, Merkel PA11, Moosig F12, Specks U13, Weller PF14, Wechsler ME15. J Allergy Clin Immunol. 2018 Dec 19. pii: S0091-6749(18)32783-0. doi: 10.1016/j.jaci.2018.11.041. [Epub ahead of print]

Abstract

Author information 1 Respiratory TAU & Flexible Discovery Unit, GSK, Philadelphia, PA, USA. 2 Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA. 3 Research and Development, Immuno-Inflammation TAU, GSK, Stockley Park West, Uxbridge, Middlesex, UK. 4 Research & Development, Statistics, Programming and Data Standards, GSK, Stockley Park West, Uxbridge, Middlesex, UK. 5 Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, La Jolla, CA, USA. 6 Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. 7 Departments of Dermatology and Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. 8 Department of Medicine, University of Cambridge, Cambridge, UK. 9 Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 10 Department of Rheumatic and Immunologic Diseases, Center for Vasculitis Care and Research, Cleveland Clinic, Cleveland, OH, USA. 11 Division of Rheumatology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA. 12 Rheumazentrum, Schleswig-Holstein Mitte, Neumünster, Germany. 13 Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA. 14 Divisions of Allergy and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston. 15 Department of Medicine, National Jewish Health, Denver, CO, USA. Electronic address: WechslerM@NJHealth.org.

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.