PMID- 34389506 OWN - NLM STAT- MEDLINE DCOM- 20211229 LR - 20220531 IS - 2213-2201 (Electronic) VI - 9 IP - 12 DP - 2021 Dec TI - Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study. PG - 4431-4440.e1 LID - S2213-2198(21)00891-6 [pii] LID - 10.1016/j.jaip.2021.07.050 [doi] AB - BACKGROUND: A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor alpha-negative hypereosinophilic syndrome (HES) and two or more flares in the previous year. OBJECTIVE: To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. METHODS: Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. RESULTS: Of 104 patients who completed the double-blind study, 98% (previous placebo, n = 52; previous mepolizumab, n = 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n = 14; previous mepolizumab, n = 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab. CONCLUSIONS: Extended mepolizumab treatment was associated with a positive benefit-risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor alpha-negative HES. CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gleich, Gerald J AU - Gleich GJ AD - Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah; Department of Medicine, School of Medicine, University of Utah, Salt Lake City, Utah. FAU - Roufosse, Florence AU - Roufosse F AD - Department of Internal Medicine, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. Electronic address: froufoss@ulb.ac.be. FAU - Chupp, Geoffrey AU - Chupp G AD - Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Conn. FAU - Faguer, Stanislas AU - Faguer S AD - Department of Nephrology and Transplantation of Organs, CHU de Toulouse, Toulouse, France. FAU - Walz, Bastian AU - Walz B AD - Department of Internal Medicine, Rheumatology, and Immunology, Medius Kliniken, University of Tubingen, Kirchheim-Teck, Germany. FAU - Reiter, Andreas AU - Reiter A AD - Department of Hematology and Oncology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany. FAU - Yancey, Steven W AU - Yancey SW AD - Respiratory Therapeutic Area, GSK, Research Triangle Park, NC. FAU - Bentley, Jane H AU - Bentley JH AD - Clinical Statistics, GSK, Brentford, Middlesex, UK. FAU - Steinfeld, Jonathan AU - Steinfeld J AD - Respiratory Research and Development, GSK, Collegeville, Pa. CN - HES Mepolizumab Study Group LA - eng SI - ClinicalTrials.gov/NCT03306043 SI - ClinicalTrials.gov/NCT02836496 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210810 PL - United States TA - J Allergy Clin Immunol Pract JT - The journal of allergy and clinical immunology. In practice JID - 101597220 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 90Z2UF0E52 (mepolizumab) SB - IM MH - Adrenal Cortex Hormones MH - *Antibodies, Monoclonal, Humanized MH - Double-Blind Method MH - Eosinophils MH - Humans MH - *Hypereosinophilic Syndrome/drug therapy MH - Treatment Outcome OTO - NOTNLM OT - Anti-IL-5 OT - Efficacy OT - Flare OT - Hypereosinophilic syndrome OT - Mepolizumab OT - Oral corticosteroid OT - Safety FIR - Garcia, Gabriel Ricardo IR - Garcia GR FIR - Pascale, Pablo IR - Pascale P FIR - Wehbe, Luis IR - Wehbe L FIR - Blockmans, Daniel IR - Blockmans D FIR - Roufosse, Florence IR - Roufosse F FIR - Antila, Martti Anton IR - Antila MA FIR - Blanco, Daniela IR - Blanco D FIR - Francisco Pez, Andreia Luisa IR - Francisco Pez AL FIR - Faguer, Stanislas IR - Faguer S FIR - Kahn, Jean-Emmanuel IR - Kahn JE FIR - Lefevre, Guillaume IR - Lefevre G FIR - Neel, Antoine IR - Neel A FIR - Kern, Peter M IR - Kern PM FIR - Reiter, Andreas J IR - Reiter AJ FIR - Walz, Bastian IR - Walz B FIR - Welte, Tobias IR - Welte T FIR - Pane, Fabrizio IR - Pane F FIR - Vannucchi, Alessandro M IR - Vannucchi AM FIR - Cerino-Javier, Ruth IR - Cerino-Javier R FIR - Hernandez-Colin, Dante D IR - Hernandez-Colin DD FIR - Valdez-Lopez, Hector Glenn IR - Valdez-Lopez HG FIR - Kuprys-Lipinska, Izabela R IR - Kuprys-Lipinska IR FIR - Musial, Jacek IR - Musial J FIR - Mihaly, Eniko IR - Mihaly E FIR - Popov, Viola Maria IR - Popov VM FIR - Ivanov, Vladimir IR - Ivanov V FIR - Tsyba, Nikolay IR - Tsyba N FIR - Cid, Maria C IR - Cid MC FIR - Fox, Maria Laura IR - Fox ML FIR - Santillana, Guillermo Sanz IR - Santillana GS FIR - Wardlaw, Andrew J IR - Wardlaw AJ FIR - Akuthota, Praveen IR - Akuthota P FIR - Butterfield, Joseph H IR - Butterfield JH FIR - Chupp, Geoffrey L IR - Chupp GL FIR - Gleich, Gerald J IR - Gleich GJ FIR - Jhaveri, Devi IR - Jhaveri D FIR - Rothenberg, Marc E IR - Rothenberg ME EDAT- 2021/08/15 06:00 MHDA- 2021/12/30 06:00 CRDT- 2021/08/14 05:47 PHST- 2021/05/25 00:00 [received] PHST- 2021/07/12 00:00 [revised] PHST- 2021/07/23 00:00 [accepted] PHST- 2021/08/15 06:00 [pubmed] PHST- 2021/12/30 06:00 [medline] PHST- 2021/08/14 05:47 [entrez] AID - S2213-2198(21)00891-6 [pii] AID - 10.1016/j.jaip.2021.07.050 [doi] PST - ppublish SO - J Allergy Clin Immunol Pract. 2021 Dec;9(12):4431-4440.e1. doi: 10.1016/j.jaip.2021.07.050. Epub 2021 Aug 10.