Long-term Clinical Outcomes of High Dose Mepolizumab Treatment for Hypereosinophilic Syndrome

Publication date: Available online 8 May 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Fei Li Kuang, Michael P. Fay, JeanAnne Ware, Lauren Wetzler, Nicole Holland-Thomas, Thomas Brown, Hector Ortega, Jonathan Steinfeld, Paneez Khoury, Amy D. Klion
BackgroundConventional therapies for hypereosinophilic syndromes (HES) have variable efficacy and carry significant long-term toxicities. Anti-IL5 (mepolizumab) therapy has a glucocorticoid (GC)-sparing effect in GC-sensitive HES, but the efficacy of mepolizumab in treatment-refractory HES patients with severe disease has not been examined to date.ObjectiveTo identify predictors of response to mepolizumab in subjects with severe treatment-refractory HES and compare long-term outcomes in these subjects to HES subjects treated with conventional therapies.MethodsRetrospective analysis of clinical and laboratory data from 35 HES subjects treated with mepolizumab and 55 HES subjects on conventional therapy, all followed at a single center.ResultsPeak eosinophilia, GC sensitivity, pulmonary involvement, HES clinical subtype and pre-treatment serum IL-5 correlated with mepolizumab response. Despite evidence of more severe disease at baseline, mepolizumab-treated subjects had comparable long-term clinical outcomes to HES subjects treated with conventional therapies and reported improvements in therapy-related comorbidities. Subjects managed with mepolizumab monotherapy had fewer disease flares than HES subjects on conventional therapies or mepolizumab-treated HES subjects requiring additional HES therapies.ConclusionsThis study confirms that mepolizumab is an effective and well-tolerated therapy for HES, but suggests that response is more likely in GC-responsive subjects with idiopathic or overlap forms of HES. A primary benefit of treatment is reduction of comorbidity due to discontinuation or reduction of conventional HES therapies. Although subjects who completely discontinued GC had the most benefit, high dose mepolizumab was a safe and effective salvage therapy for severe, treatment-refractory HES.