Food, drug, insect sting allergy, and anaphylaxis
Reslizumab in children and adolescents with eosinophilic esophagitis: Results of a double-blind, randomized, placebo-controlled trial

https://doi.org/10.1016/j.jaci.2011.11.044Get rights and content

Background

Eosinophilic esophagitis is a chronic allergic disease with insufficient treatment options. Results from animal studies suggest that IL-5 induces eosinophil trafficking in the esophagus.

Objective

We sought to evaluate the effect of reslizumab, a neutralizing antibody against IL-5, in children and adolescents with eosinophilic esophagitis.

Methods

Patients with symptom severity scores of moderate or worse and an esophageal biopsy specimen with 24 or more intraepithelial eosinophils per high-power field were randomly assigned to receive infusions of 1, 2, or 3 mg/kg reslizumab or placebo at weeks 0, 4, 8, and 12. The coprimary efficacy measures were changes in peak esophageal eosinophil count and the physician’s global assessment score at week 15 (end of therapy).

Results

Two-hundred twenty-six patients received study medication. Median reductions from baseline to the end of therapy in peak esophageal eosinophil counts were 59%, 67%, 64%, and 24% in the 1, 2, and 3 mg/kg reslizumab (all P < .001) and placebo groups, respectively. All treatment groups, including the placebo group, showed improvements in physician’s global assessment scores; the differences between the reslizumab and placebo groups were not statistically significant. The most common adverse events in the reslizumab groups were headache, cough, nasal congestion, and upper respiratory tract infection. One patient in each reslizumab group and 2 in the placebo group had serious adverse events; none were considered related to the study medication.

Conclusion

Reslizumab significantly reduced intraepithelial esophageal eosinophil counts in children and adolescents with eosinophilic esophagitis. However, improvements in symptoms were observed in all treatment groups and were not associated with changes in esophageal eosinophil counts.

Section snippets

Patients

Male or female children and adolescents aged between 5 and 18 years with active eosinophilic esophagitis were eligible to participate in the study. Patients must have had at least 1 active symptom (ie, vomiting, regurgitation, abdominal pain, chest pain/heartburn, or dysphagia) of moderate severity or worse (as assessed by the patient) within the week before randomization, an esophagogastroduodenoscopy with biopsy documenting active eosinophilic esophagitis (defined as ≥24 eosinophils in ≥1

Study population

Of the 227 patients who were randomly assigned to treatment, 1 did not receive study medication (Fig 1). Thus 226 patients were included in the efficacy and safety analyses. Most patients were male and had a history of atopic disease (Table I). All patients had 24 or more esophageal eosinophils in the peak hpf at baseline, and the median number was 80.0 eosinophils/hpf for the population as a whole, with a range of 24 to 453 eosinophils/hpf.

Two patients in the 1 mg/kg reslizumab group, 3

Discussion

We evaluated the effect of reslizumab, an antibody to IL-5, in children and adolescents with eosinophilic esophagitis. The study population consisted of patients with long-standing disease, a mean of 4 years of eosinophilic esophagitis symptoms, and significant esophageal eosinophilia. Patients who received reslizumab showed statistically significant and clinically relevant reductions in esophageal eosinophil counts compared with those who received placebo. However, these reductions were not

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  • Cited by (0)

    Sponsored by Ception Therapeutics, Inc, which has since been acquired by Cephalon, Inc.

    Disclosure of potential conflict of interest: J. M. Spergel is a consultant for DBV; has received research support from the Department of Defense (DOD), Cephalon, and the National Institutes of Health (NIH); is a member of the American Academy of Allergy, Asthma & Immunology; and is on the American Partnership for Eosinophilic Disorders (APFED) Medical Advisory Board. M. E. Rothenberg has equity interest in reslizumab through Cephalon; is consultant and chief scientific officer of Immune Pharmaceuticals; has received research support from the NIH, the Food Allergy & Anaphylaxis Network, and the DOD; is on the APFED Medical Advisory Board; and is on the International Eosinophil Society Executive Council. M. H. Collins is a central review pathologist for Cephalon, GlaxoSmithKline, and Meritage Pharma; is a consultant for Sunovion; and is president of the APFED Medical Advisory Board. G. T. Furuta is a consultant for Nutricia and Meritage and has received research support from the NIH, AstraZeneca, and the Thrasher Foundation. G. Fuchs III has received research support from Shire and Cephalon. J. P. Abonia has received research support from the NIH, Ception Therapeutics, and the Children’s Digestive Health and Nutrition Foundation. T. Henkel is a consultant for Cephalon and a shareholder in Ception Therapeutics. C. A. Liacouras is a speaker for Nutricia and is on the American Partnership for Eosinophilic Disorders Physician Board. The rest of the authors declare that they have no relevant conflicts of interest.

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