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. (C) 2021 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study / Gleich, Gerald J; Roufosse, Florence; Chupp, Geoffrey; Faguer, Stanislas; Walz, Bastian; Reiter, Andreas; Yancey, Steven W; Bentley, Jane H; Steinfeld, Jonathan; HES Mepolizumab Study Group: Gabriel Ricardo García, Pablo Pascale, Luis Wehbe, Daniël Blockmans, Florence Roufosse, Martti Anton Antila, Daniela Blanco, Andreia Luisa Francisco Pez, Stanislas Faguer, Jean-Emmanuel Kahn, Guillaume Lefévre, Antoine Neel, Peter M Kern, Andreas J Reiter, Bastian Walz, Tobias Welte, Fabrizio Pane, Alessandro M Vannucchi, Ruth Cerino-Javier, Dante D Hernández-Colín, Héctor Glenn Valdéz-López, Izabela R Kupryś-Lipińska, Jacek Musial, Eniko Mihaly, Viola Maria Popov, Vladimir Ivanov, Nikolay Tsyba, Maria C Cid, Maria Laura Fox, Guillermo Sanz Santillana, Andrew J Wardlaw, Praveen Akuthota, Joseph H Butterfield, Geoffrey L Chupp, Gerald J Gleich, Devi Jhaveri, Marc E Rothenberg. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE. - ISSN 2213-2198. - ELETTRONICO. - 9:(2021), pp. 4431-4440.e1. [10.1016/j.jaip.2021.07.050]
Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study
Alessandro M Vannucchi;
2021
Abstract
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. (C) 2021 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
