Biologic Agents for the Treatment of Hypereosinophilic Syndromes

Abstract

Hypereosinophilic syndromes (HES) are a heterogeneous group of rare disorders defined by the presence of marked peripheral or tissue eosinophilia resulting in end organ damage. Although conventional therapies, including glucocorticoids, hydroxyurea, and interferon-α, are initially effective in reducing eosinophilia and symptoms in a majority of patients with platelet-derived growth factor (PDGFR) mutation-negative HES, development of resistance and treatment-related toxicity are common. In contrast, targeted therapy with the tyrosine kinase inhibitor, imatinib, is well-tolerated but effective only in the subset of HES patients with a primary myeloid disorder. Eosinophil-targeted biotherapeutics offer the potential of improved efficacy with few, if any, adverse effects. The aims of this review are to provide an overview of current approaches to the use of conventional HES therapies and a discussion of existing biotherapeutics that target eosinophils and their potential use in the treatment of HES. With the continuing expansion of eosinophil-targeted biotherapeutics, the future for patients with eosinophilic disorders is promising.

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

“…At a minimum, withdrawal of corticosteroids did not result in worsening of vasculitis as has occurred with various other steroid‐sparing medications used for asthma . Although not yet approved for use in eosinophilic disorders other than asthma and EGPA, there is strong evidence that mepolizumab (and other biologics targeting the IL‐5 axis) have clinically beneficial activity in HES, lymphoid HES, and perhaps EGID . Since their cost and the paucity of available data, including uncertainty on optimal dosing, are likely to make off‐label use in these disorders difficult, the importance of well‐designed clinical trials, especially in rare EAD, remains a priority.…”

“…123 Although not yet approved for use in eosinophilic disorders other than asthma and EGPA, there is strong evidence that mepolizumab (and other biologics targeting the IL-5 axis) have clinically beneficial activity in HES, lymphoid HES, and perhaps EGID. 122,124 Since their cost and the paucity of available data, including uncertainty on optimal dosing, are likely to make off-label use in these disorders difficult, the importance of well-designed clinical trials, especially in rare EAD, remains a priority. Moreover, as the number of approved targeted agents increases, direct comparisons between the different agents and the safety and efficacy of combination therapies will be essential to create optimized outcomes based recommendations to help guide physicians.…”

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

“…Hypereosinophilic syndromes are rare and often debilitating chronic inflammatory disorders characterized by blood and tissue eosinophilia, with associated eosinophil-mediated organ damage and/or dysfunction. These disorders are currently classified on the basis of underlying molecular and immunological defects and the spectrum of target organ damage ( 65 , 66 ) [see Kahn in this research topic ( 67 )]. Although the mechanisms resulting in eosinophil expansion remain unknown in the majority of patients (“idiopathic” HES variant), the role played by eosinophils in tissue damage is undeniable and targeting the IL-5 pathway makes sense.…”

Skin-limited idiopathic hypereosinophilic syndrome presenting with retiform purpura

“…However, pre-existing areas of ischemia and ulceration remained unimproved. Steroid tapering was continued on an outpatient basis, with hydroxyurea 500 mg daily added for steroid-sparing antieosinopoietic effect (used effectively in PDGFR mutation–negative IHES requiring prednisone) 6 …”