Inhibition of Interleukin-5 in Eosinophilic Esophagitis leads to histological improvement
Published Online: December 30, 2011
Eosinophilic esophagitis is a disease characterized by high levels of white blood cells called eosinophils in the esophagus. Patients with eosinophilic esophagitis experience vomiting, chest pain, difficulty swallowing, tissue remodeling, and stricture formation. Management options for eosinophilic esophagitis, including dietary restriction, elemental formula supplements, or topical or systemic corticosteroids, are limited because of long-term safety concerns and difficulty with compliance. Effective, well-tolerated therapies for eosinophilic esophagitis would make patients more likely to adhere to the prescribed treatment regimen and allow them to avoid adverse effects of corticosteroids. Interleukin-5 (IL-5) induces eosinophil trafficking in the esophagus and is involved in the maturation, recruitment, and activation of eosinophils. Reslizumab, a humanized monoclonal antibody to IL-5, neutralizes circulating IL-5 by preventing it from binding to its receptor.
In a study published in The Journal of Allergy and Clinical Immunology (JACI), Spergel et al evaluated the effect of reslizumab on children and adolescents with eosinophilic esophagitis. Two hundred twenty-six patients with active eosinophilic esophagitis and an esophageal biopsy with ≥24 eosinophils in at least one high power field were randomly assigned to receive 4 monthly infusions of reslizumab 1, 2, or 3 mg/kg or placebo. Peak esophageal eosinophil counts and physicians’ global assessments of symptoms were conducted at week 15.
The researchers observed statistically significant and clinically relevant reductions in peak esophageal eosinophil counts in patients who received reslizumab compared with those who received placebo. However, no significant differences were observed between the reslizumab and placebo groups in the changes in physicians’ global assessments; patients in all treatment groups, including placebo, showed improvements from baseline. Reslizumab was generally well tolerated with no specific adverse event consistently more common in the reslizumab groups than in the placebo group. Five patients had serious adverse events, including 1 in each of the reslizumab groups and 2 in the placebo group, but none were considered by the investigators to be related to study medication.
The results of this study were similar to those of other, smaller studies of antibodies to IL-5 in adult and pediatric patients with eosinophilic esophagitis. Although patients who received reslizumab showed significant reductions in esophageal eosinophils after treatment, most did not experience complete clearing of eosinophils from the esophagus. The researchers recommended that future studies should evaluate the effect of longer treatment duration on esophageal eosinophils to determine if further reductions in eosinophilia can be attained. Furthermore, the symptom assessment tools in this study have not been previously validated, so the researchers indicated that the symptom results of the study should be interpreted with caution. Because of the difficulties associated with assessing symptoms of patients with eosinophilic esophagitis in the context of a clinical trial, the researchers recommended that future studies should focus on changes in esophageal biopsies.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.