Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti–IL-5 antibody SCH55700

Background

Hypereosinophilic syndrome and eosinophilic gastroenteritis with peripheral eosinophilia are characterized by sustained eosinophilia and eosinophil-mediated tissue damage. Although treatment with the humanized monoclonal anti–IL-5 antibody SCH55700 resulted in improvement of eosinophilia and clinical symptoms in 6 of 8 of patients with hypereosinophilic syndrome or eosinophilic gastroenteritis with peripheral eosinophilia for as long as 12 weeks, eosinophil counts subsequently rose above baseline levels, accompanied by an exacerbation of symptoms.

Objective

To identify the mechanism underlying this rebound eosinophilia.

Methods

Purified eosinophils from patients or normal donors were cultured with IL-5, patient serum, and/or anticytokine antibodies, and eosinophil survival was assessed by flow cytometry. Serum and intracellular cytokine levels were measured by multiplex sandwich ELISA and flow cytometry, respectively.

Results

Before treatment with SCH55700, in vitro eosinophil survival in media and in response to recombinant IL-5 was similar in patients and normal donors. At 1 month posttreatment, the eosinophil survival curves were unchanged in 4 of 5 patients in media and in all 5 patients in response to recombinant IL-5. Normal eosinophil survival was prolonged in cultures containing posttreatment but not pretreatment sera (pretreatment vs posttreatment, 10.74% vs 73.02% live cells; P=.01). This posttreatment serum effect on eosinophil survival was reversed by the addition of the monoclonal anti–IL-5 antibody TRFK5. Although increased levels of serum IL-5 were observed at 1 month compared with 2 to 3 days posttreatment in 5 of 6 patients (P=.04), intracellular cytokine analysis did not reveal increased production of IL-5 by peripheral blood mononuclear cells.

Conclusions

The rebound eosinophilia after SCH55700 treatment is a result of a serum factor that enhances eosinophil survival. Reversal of this effect by the addition of antibody to IL-5 suggests that this factor may be IL-5 itself.

Key words: Anti–IL-5, hypereosinophilic syndrome, eosinophilic gastroenteritis, monoclonal antibody, eosinophil

Abbreviations used: EG, Eosinophilic gastroenteritis, EGE, Eosinophilic gastroenteritis with peripheral eosinophilia, HES, Hypereosinophilic syndrome