Table 4.

Selected therapeutic agents for the treatment of hypereosinophilic syndromes

Class	Selected agents	Target	Comments
CS	Oral prednisone and equivalents Topical CS (ie, swallowed budesonide)	NA	First-line therapy in most types of HES; although most patients respond initially, toxicity and resistance are limiting long term May be sufficient in single-organ eosinophilic disorders, such as eosinophilic esophagitis, and eosinophilic dermatitis
Cytotoxic	Hydroxyurea Methotrexate Cyclophosphamide	Dividing cells	Conventional second-line therapy for idiopathic HES* and some MHES; can be used at high dose to rapidly lower counts; inexpensive but significant toxicity Steroid-sparing agent most commonly used in EGPA and other rheumatologic overlap disorders* Mostly used for steroid-refractory or life-threatening EGPA
Immunomodulatory	Interferon α Cyclosporine		Conventional second-line therapy for LHES and some idiopathic HES; substantial toxicity* Alternative second-line agent, especially in LHES; renal toxicity is a significant problem*
Biologics	Mepolizumab* Reslizumab Benralizumab Dupilumab Lirentelimab	IL-5 IL-5 IL-5 receptor IL-4 receptor Siglec-8	Approved for the treatment of HES and EGPA at 300 mg monthly19,21 Likely to be comparable to mepolizumab; approved for asthma with weight-based dosing In phase 3 trials for HES; approved for asthma Blocks tissue eosinophilia but may cause peripheral eosinophilia and, rarely, eosinophilic complications; approved for chronic rhinosinusitis, atopic dermatitis, and, most recently, eosinophilic esophagitis Depletes eosinophils and prevents mast cell degranulation; in clinical development
Tyrosine kinase inhibitors	Imatinib Ruxolitinib	Multiple JAK	Approved for the treatment of HES; near 100% efficacy in PDGFR-associated myeloid neoplasms; some efficacy in other HES with myeloid features17 Approved for several myeloid disorders typically associated with JAK2 mutations; case reports suggest that it may be useful in JAK2-associated HES and LHES
Novel targeted	Dexpramipexole	Causes maturational arrest at eosinophilic promyelocyte stage via unknown mechanism	In clinical development for HES; phase 2 study promising

^* Mepolizumab, which is approved for the treatment of HES, has better efficacy and lower toxicity but is expensive and not available in all countries.

^† Primary outcome of the phase 3 trial of mepolizumab for PDGFRA-negative, steroid-responsive HES in adults: reduction of disease flares over a 32-week period in patients receiving mepolizumab and stable background therapy compared with those receiving placebo and stable background therapy.²¹ Dual primary outcomes of the phase 3 trial of mepolizumab for relapsing or treatment-refractory EGPA in adults: total accrued weeks of remission, defined as a Birmingham vasculitis score of 0 on less than 4 mg prednisone daily for 52 weeks, and proportion of participants in remission at weeks 36 and 48.²³

CS, corticosteroid; EGPA, eosinophilic granulomatosis and polyangiitis; MHES, myeloid variant hypereosinophilic syndrome.