Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study

Gleich, G. J.; Roufosse, F.; Chupp, G.; Faguer, S.; Walz, B.; Reiter, A.; Yancey, S. W.; Bentley, J. H.; Steinfeld, J.; Garcia, G. R.; Pascale, P.; Wehbe, L.; Blockmans, D.; Antila, M. A.; Blanco, D.; Francisco Pez, A. L.; Kahn, J. -E.; Lefevre, G.; Neel, A.; Kern, P. M.; Reiter, A. J.; Welte, T.; Pane, F.; Vannucchi, A. M.; Cerino-Javier, R.; Hernandez-Colin, D. D.; Valdez-Lopez, H. G.; Kuprys-Lipinska, I. R.; Musial, J.; Mihaly, E.; Popov, V. M.; Ivanov, V.; Tsyba, N.; Cid, M. C.; Fox, M. L.; Santillana, G. S.; Wardlaw, A. J.; Akuthota, P.; Butterfield, J. H.; Chupp, G. L.; Jhaveri, D.; Rothenberg, M. E.

doi:10.1016/j.jaip.2021.07.050

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 α–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 α–negative HES.

Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study / Gleich, G. J.; Roufosse, F.; Chupp, G.; Faguer, S.; Walz, B.; Reiter, A.; Yancey, S. W.; Bentley, J. H.; Steinfeld, J.; Garcia, G. R.; Pascale, P.; Wehbe, L.; Blockmans, D.; Antila, M. A.; Blanco, D.; Francisco Pez, A. L.; Kahn, J. -E.; Lefevre, G.; Neel, A.; Kern, P. M.; Reiter, A. J.; Welte, T.; Pane, F.; Vannucchi, A. M.; Cerino-Javier, R.; Hernandez-Colin, D. D.; Valdez-Lopez, H. G.; Kuprys-Lipinska, I. R.; Musial, J.; Mihaly, E.; Popov, V. M.; Ivanov, V.; Tsyba, N.; Cid, M. C.; Fox, M. L.; Santillana, G. S.; Wardlaw, A. J.; Akuthota, P.; Butterfield, J. H.; Chupp, G. L.; Jhaveri, D.; Rothenberg, M. E.. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE. - ISSN 2213-2198. - 9:12(2021), pp. 4431-4440. [10.1016/j.jaip.2021.07.050]