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 - Funding Information:
Editorial support (in the form of writing assistance, including development of the initial draft, assembling tables and figures, collating authors comments, grammatical editing, and referencing) was provided by Natasha Dean, MSc, and Elizabeth Hutchinson, PhD, CMPP, at Fishawack Indicia and was funded by GlaxoSmithKline.
Funding Information:
This study was funded by GlaxoSmithKline (GSK ID 115921 ClinicalTrials.gov number NCT02020889), the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID; U01 AI097073) and in part by the Division of Intramural Research, NIH/NIAID. The post hoc analysis of 115921/NCT02020889 presented in this article was funded by GlaxoSmithKline.Disclosure of potential conflict of interest: J. Steinfeld, E. S. Bradford, J. Brown, S. Mallett, and S. W. Yancey are employees of GlaxoSmithKline and own stocks in GlaxoSmithKline. P. Akuthota has received research grants from GlaxoSmithKline and the National Institutes of Health (NIH) and has acted as a consultant for Ambrx, GlaxoSmithKline, and AstraZeneca. M. C. Cid has acted as a consultant for GlaxoSmithKline, Novartis, and Roche. G. J. Gleich has received research grants from the NIH and has acted as a consultant for Genentech. D. Jayne has received research grants from GlaxoSmithKline and acted as a consultant for GlaxoSmithKline. C. A. Langford has received research grants from Bristol-Myers Squibb, Genentech, ChemoCentryx, and GlaxoSmithKline and is a nonpaid consultant for Bristol-Myers Squibb and Abbvie. P. A. Merkel has received research funds and/or consulting fees from Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche, GlaxoSmithKline, InflaRx, Insmed, Kypha, and TerumoBCT. F. Moosig has received research grants from Roche and has acted as a consultant for Chugai, GlaxoSmithKline, Lilly, and Roche. P. F. Weller has received research grants from the NIH and acted as a consultant for GlaxoSmithKline. M. E. Wechsler has acted as a consultant for AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi, Sentien, Teva, and Vectura and has received research funding from Teva, AstraZeneca, Novartis and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest. This study was funded by GlaxoSmithKline (GSK ID 115921 ClinicalTrials.gov number NCT02020889), the National Institutes of Health (NIH)/ National Institute of Allergy and Infectious Diseases (NIAID; U01 AI097073) and in part by the Division of Intramural Research, NIH/ NIAID. The post hoc analysis of 115921/ NCT02020889 presented in this article was funded by GlaxoSmithKline. Disclosure of potential conflict of interest: J. Steinfeld, E. S. Bradford, J. Brown, S. Mallett, and S. W. Yancey are employees of GlaxoSmithKline and own stocks in GlaxoSmithKline. P. Akuthota has received research grants from GlaxoSmithKline and the National Institutes of Health (NIH) and has acted as a consultant for Ambrx, GlaxoSmithKline, and AstraZeneca. M. C. Cid has acted as a consultant for GlaxoSmithKline, Novartis, and Roche. G. J. Gleich has received research grants from the NIH and has acted as a consultant for Genentech. D. Jayne has received research grants from GlaxoSmithKline and acted as a consultant for GlaxoSmithKline. C. A. Langford has received research grants from Bristol-Myers Squibb, Genentech, ChemoCentryx, and GlaxoSmithKline and is a nonpaid consultant for Bristol-Myers Squibb and Abbvie. P. A. Merkel has received research funds and/or consulting fees from Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche, GlaxoSmithKline, InflaRx, Insmed, Kypha, and TerumoBCT. F. Moosig has received research grants from Roche and has acted as a consultant for Chugai, GlaxoSmithKline, Lilly, and Roche. P. F. Weller has received research grants from the NIH and acted as a consultant for GlaxoSmithKline. M. E. Wechsler has acted as a consultant for AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi, Sentien, Teva, and Vectura and has received research funding from Teva, AstraZeneca, Novartis and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest. Editorial support (in the form of writing assistance, including development of the initial draft, assembling tables and figures, collating authors comments, grammatical editing, and referencing) was provided by Natasha Dean, MSc, and Elizabeth Hutchinson, PhD, CMPP, at Fishawack Indicia and was funded by GlaxoSmithKline. This study was funded by GlaxoSmithKline (GSK ID 115921 ClinicalTrials.gov number NCT02020889), the National Institutes of Health (NIH)/ National Institute of Allergy and Infectious Diseases (NIAID; U01 AI097073) and in part by the Division of Intramural Research, NIH/ NIAID. The post hoc analysis of 115921/ NCT02020889 presented in this article was funded by GlaxoSmithKline. Disclosure of potential conflict of interest: J. Steinfeld, E. S. Bradford, J. Brown, S. Mallett, and S. W. Yancey are employees of GlaxoSmithKline and own stocks in GlaxoSmithKline. P. Akuthota has received research grants from GlaxoSmithKline and the National Institutes of Health (NIH) and has acted as a consultant for Ambrx, GlaxoSmithKline, and AstraZeneca. M. C. Cid has acted as a consultant for GlaxoSmithKline, Novartis, and Roche. G. J. Gleich has received research grants from the NIH and has acted as a consultant for Genentech. D. Jayne has received research grants from GlaxoSmithKline and acted as a consultant for GlaxoSmithKline. C. A. Langford has received research grants from Bristol-Myers Squibb, Genentech, ChemoCentryx, and GlaxoSmithKline and is a nonpaid consultant for Bristol-Myers Squibb and Abbvie. P. A. Merkel has received research funds and/or consulting fees from Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche, GlaxoSmithKline, InflaRx, Insmed, Kypha, and TerumoBCT. F. Moosig has received research grants from Roche and has acted as a consultant for Chugai, GlaxoSmithKline, Lilly, and Roche. P. F. Weller has received research grants from the NIH and acted as a consultant for GlaxoSmithKline. M. E. Wechsler has acted as a consultant for AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi, Sentien, Teva, and Vectura and has received research funding from Teva, AstraZeneca, Novartis and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest.
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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UR - http://www.scopus.com/inward/citedby.url?scp=85060347363&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2018.11.041
DO - 10.1016/j.jaci.2018.11.041
M3 - Article
C2 - 31056188
AN - SCOPUS:85060347363
VL - 143
SP - 2170
EP - 2177
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 6
ER -