For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.
Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in .
EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.
In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).
In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.
Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”
The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.
SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. .