Florence Roufosse1, Jean-Emmanuel Kahn2, Marc E Rothenberg3, Andrew J Wardlaw4, Amy D Klion5, Suyong Yun Kirby6, Martyn J Gilson7, Jane H Bentley8, Eric S Bradford6, Steven W Yancey6, Jonathan Steinfeld9, Gerald J Gleich10. 1. Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: froufoss@ulb.ac.be. 2. Department of Internal Medicine, Hôpital Ambroise Paré, Université Versailles-Saint Quentin-en-Yvelines, Boulogne-Billancourt, France. 3. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio. 4. Institute for Lung Health, University of Leicester, Leicester, United Kingdom. 5. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. 6. Respiratory Therapeutic Area, GSK, Research Triangle Park, NC. 7. Respiratory Research and Development, GSK, Uxbridge, Middlesex, United Kingdom. 8. Clinical Statistics, GSK, Uxbridge, Middlesex, United Kingdom. 9. Respiratory Research & Development, GSK, Collegeville, Pa. 10. Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah.
Abstract
BACKGROUND: Anti-IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear. OBJECTIVE: We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES. METHODS: This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed. RESULTS: The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]). CONCLUSIONS: Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.
BACKGROUND: Anti-IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear. OBJECTIVE: We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES. METHODS: This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed. RESULTS: The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]). CONCLUSIONS: Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.
Authors: Marc E Rothenberg; Amy D Klion; Florence E Roufosse; Jean Emmanuel Kahn; Peter F Weller; Hans-Uwe Simon; Lawrence B Schwartz; Lanny J Rosenwasser; Johannes Ring; Elaine F Griffin; Ann E Haig; Paul I H Frewer; Jacqueline M Parkin; Gerald J Gleich Journal: N Engl J Med Date: 2008-03-16 Impact factor: 91.245
Authors: Florence E Roufosse; Jean-Emmanuel Kahn; Gerald J Gleich; Lawrence B Schwartz; Anish D Singh; Lanny J Rosenwasser; Judah A Denburg; Johannes Ring; Marc E Rothenberg; Javed Sheikh; Ann E Haig; Stephen A Mallett; Deborah N Templeton; Hector G Ortega; Amy D Klion Journal: J Allergy Clin Immunol Date: 2012-10-04 Impact factor: 10.793
Authors: Jennifer K Garrett; Sean C Jameson; Blythe Thomson; Margaret H Collins; Lynne E Wagoner; Debbie K Freese; Lisa A Beck; Joshua A Boyce; Alexandra H Filipovich; Joyce M Villanueva; Steven A Sutton; Amal H Assa'ad; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2003-12-12 Impact factor: 10.793
Authors: Ian D Pavord; Stephanie Korn; Peter Howarth; Eugene R Bleecker; Roland Buhl; Oliver N Keene; Hector Ortega; Pascal Chanez Journal: Lancet Date: 2012-08-18 Impact factor: 79.321
Authors: Michael M Chen; Florence Roufosse; Sa A Wang; Srdan Verstovsek; Sandy R Durrani; Marc E Rothenberg; Thanai Pongdee; Joseph Butterfield; Timothy Lax; Michael E Wechsler; Miguel L Stein; Princess U Ogbogu; Basil M Kahwash; Sameer K Mathur; Dagmar Simon; Praveen Akuthota; Nicole Holland; Lauren Wetzler; JeanAnne M Ware; Canting Guo; Michael P Fay; Paneez Khoury; Amy D Klion; Bruce S Bochner Journal: J Allergy Clin Immunol Pract Date: 2022-02-15
Authors: Ian D Pavord; Elisabeth H Bel; Arnaud Bourdin; Robert Chan; Joseph K Han; Oliver N Keene; Mark C Liu; Neil Martin; Alberto Papi; Florence Roufosse; Jonathan Steinfeld; Michael E Wechsler; Steven W Yancey Journal: Allergy Date: 2021-09-16 Impact factor: 14.710
Authors: Elizabeth A Jacobsen; David J Jackson; Enrico Heffler; Sameer K Mathur; Albert J Bredenoord; Ian D Pavord; Praveen Akuthota; Florence Roufosse; Marc E Rothenberg Journal: Annu Rev Immunol Date: 2021-03-01 Impact factor: 28.527
Authors: Enrico Ammirati; Emanuele Bizzi; Giacomo Veronese; Matthieu Groh; Caroline M Van de Heyning; Jukka Lehtonen; Marc Pineton de Chambrun; Alberto Cereda; Chiara Picchi; Lucia Trotta; Javid J Moslehi; Antonio Brucato Journal: Front Med (Lausanne) Date: 2022-03-07