Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5

Mepolizumab in Hypereosinophilic Syndromes: Proposed Therapeutic Algorithm

“…In the current study, Rothenberg and colleagues 13 performed a post hoc analysis using data from the phase III study NCT02836496 to define whether baseline peripheral blood eosinophil counts and/or serum IL-5 levels in patients with HES would predict responses to mepolizumab. In their study, patients aged 12 years and greater with HES (or a HES-like condition) known for at least 6 months, with two or more flares (found in the previous 12 months) and an eosinophil count of 1,000/mL blood or greater, were enrolled.…”

“…In their study, patients aged 12 years and greater with HES (or a HES-like condition) known for at least 6 months, with two or more flares (found in the previous 12 months) and an eosinophil count of 1,000/mL blood or greater, were enrolled. 13 Patients were randomized 1:1 to either 4-weekly subcutaneous mepolizumab (300 mg) or placebo alone (plus baseline HES therapy) for a total of 32 weeks. During the observation period, flare rates and signs of fatigue were recorded and related to baseline eosinophil counts and IL-5 levels.…”

“…Overall, mepolizumab reduced the proportion of patients with one or more flare as well as fatigue in these patients, independent of the eosinophil count and of the basal IL-5 level, which was undetectable in most cases tested. 13 Based on this observation, mepolizumab may be regarded as an effective agent in patients with treatment-resistant, cytokinetriggered HES and may be recommended especially for patients with reactive or idiopathic HES complicated by flares and fatigue, regardless of eosinophil counts and IL-5 levels.…”

“…Therefore, the concept of defining an appropriate target population of patients using eosinophils as a secondary (indirect) target of therapy with mepolizumab should be based on a reliable minimal count of eosinophils. Based on the study of Rothenberg and colleagues, 13 such a minimal eosinophil count could be 1,000/mL blood in HES contexts. In other disease models, such as eosinophilic asthma, the minimal count of eosinophils indicative of predicting a response to mepolizumab appears to be even lower (150/mL blood).…”

Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome

“…Any existing standard HES therapy remained the same throughout the 32-week treatment period, unless there was a worsening of symptoms (a flare) that required an increase in therapy. Treatment was returned, where possible, to the original dosing regimen once disease control was regained ( 8 – 11 ).…”