TY - JOUR
T1 - Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis
AU - Steinfeld, Jonathan
AU - Bradford, Eric S.
AU - Brown, Judith
AU - Mallett, Stephen
AU - Yancey, Steven W.
AU - Akuthota, Praveen
AU - Cid, Maria C.
AU - Gleich, Gerald J.
AU - Jayne, David
AU - Khoury, Paneez
AU - Langford, Carol A.
AU - Merkel, Peter A.
AU - Moosig, Frank
AU - Specks, Ulrich
AU - Weller, Peter F.
AU - Wechsler, Michael E.
N1 - Publisher Copyright:
© 2018 American Academy of Allergy, Asthma & Immunology
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Churg-Strauss syndrome
KW - Eosinophilic granulomatosis with polyangiitis
KW - IL-5
KW - eosinophils
KW - mepolizumab
KW - vasculitis
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U2 - 10.1016/j.jaci.2018.11.041
DO - 10.1016/j.jaci.2018.11.041
M3 - Article
C2 - 31056188
AN - SCOPUS:85060347363
SN - 0091-6749
VL - 143
SP - 2170
EP - 2177
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -