Jonathan Steinfeld1, Eric S Bradford2, Judith Brown3, Stephen Mallett4, Steven W Yancey2, Praveen Akuthota5, Maria C Cid6, Gerald J Gleich7, David Jayne8, Paneez Khoury9, Carol A Langford10, Peter A Merkel11, Frank Moosig12, Ulrich Specks13, Peter F Weller14, Michael E Wechsler15. 1. Respiratory TAU & Flexible Discovery Unit, GlaxoSmithKline, Philadelphia, Pa. 2. Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC. 3. Research and Development, Immuno-Inflammation TAU, Uxbridge, United Kingdom. 4. Research & Development, Statistics, Programming and Data Standards, GlaxoSmithKline, Stockley Park West, Uxbridge, United Kingdom. 5. Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, La Jolla, Calif. 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, Utah. 8. Department of Medicine, University of Cambridge, Cambridge, United Kingdom. 9. Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. 10. Department of Rheumatic and Immunologic Diseases, Center for Vasculitis Care and Research, Cleveland Clinic, Cleveland, Ohio. 11. Division of Rheumatology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pa. 12. Rheumazentrum, Schleswig-Holstein Mitte, Neumünster, Germany. 13. Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minn. 14. Divisions of Allergy and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. 15. Department of Medicine, National Jewish Health, Denver, Colo. 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: 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 stableOGCs (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 150cells/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.
RCT Entities:
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.
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