LONG-TERM MAINTENANCE THERAPY WITH THE LOWEST EFFECTIVE DOSE OF ORAL VISCOUS BUDESONIDE IN PEDIATRIC EOSINOPHILIC ESOPHAGITIS

Background and aims Oral viscous budesonide (OVB) is efficacious in inducing and maintaining clinical/histological remission in pediatric Eosinophilic Esophagitis (EoE). However, it has not been established whether lowest effective dose might be identified, and whether treatment can be interrupted once patients have achieved remission after a history of frequent relapses. This study aims to identify the lowest effective dose of OVB by progressive halving dosage and to evaluate its efficacy on clinical, endoscopic and histological remission. Methods We prospectively enrolled active pediatric EoE patients (diagnosed according to the ESPGHAN criteria, J Pediatr Gastroenterol Nutr 2014;58:107-18) with a history of early relapse following topical steroids withdrawal (< 6 months). Patients received a homemade suspension of OVB prepared by mixing inhaled budesonide with viscous solutions of sodium alginate (< 150 cm: 0.5 mg bid; >150cm: 1 mg bid). After 12 weeks of induction therapy, patients achieving a complete histological remission (a peak eosinophil count of <6/HPF in all esophageal levels) underwent a maintenance remission phase halving the dose every 24 weeks up to a minimum of 0.25mg/day and 0.125mg/day (single evening administration). Endoscopy was performed at 0,12,36,60 and 84 weeks. In case of symptomatic and/or histological flare-up, patients received a step-up therapy with the previous effective dose. Clinical symptom score (CSS) (Gupta SK, Clin Gastroenterol Hepatol 2015;13:66-76), endoscopy (EoE Endoscopic Reference Score, EREFS, modified; Gut 2013;62:489-95) and histology (count of eosinophils/hpf at all esophageal levels) were evaluated. Serum cortisol was evaluated at baseline, 12,36,60 and 84 weeks. Results We enrolled 26 children (16 male, 10 female; median age 11 years, range 5-17). After 12 weeks of induction therapy with OVB, 23 patients (88%) were in clinical, endoscopic and histological remission. During the progressive halving therapy, remission was still observed in 21 (81%), 17 (65%) at 36 and 60 weeks, respectively. At the final 84-week assessment, 14 patients (54%) maintained remission by the lowest evening dose (0.25 and 0.125 mg/day). No significant difference in cortisol levels was observed during the study period. Only one oral candidiasis was recorded. Conclusions This first pediatric study on long-term maintenance therapy with OVB in pediatric EoE showed that a progressive dose reduction was effective in maintaining remission over 84 weeks. However, the lowest effective dose differs among patients and should be determined by halving the dose over the different follow-ups.