The online version of this article (https://doi.org/10.1007/s10620-018-5325-8) contains supplementary material, which is available to authorized users.
In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump inhibitor, dexlansoprazole, is approved for healing EE of all grades, maintenance of healed EE, relief of heartburn, and treatment of symptomatic non-erosive GERD in patients ≥ 12 years.
To assess safety and efficacy of dexlansoprazole dual delayed-release capsule in healing of EE and maintenance of healed EE in adolescents.
A multicenter, phase 2, 36-week study was conducted in 62 adolescents (12–17 years) with endoscopically confirmed EE. Patients received dexlansoprazole 60 mg once daily (QD) during open-label healing phase. Those with confirmed healing at week 8 were randomized to dexlansoprazole 30 mg QD or placebo during 16-week, double-blind maintenance phase, with subsequent treatment-free follow-up of ≥ 12 weeks. Primary endpoints were treatment-emergent adverse events (TEAEs) in ≥ 5% of patients during treatment. Secondary endpoints included percentages of patients with healing of EE and with maintenance of healed EE.
88% of patients achieved EE healing, and 61.3% reported a TEAE [headache (12.9%), oropharyngeal pain (8.1%), diarrhea (6.5%), and nasopharyngitis (6.5%)]. During maintenance phase, healing was maintained in 82% and 58% of dexlansoprazole and placebo groups, respectively. 72.0% of dexlansoprazole-treated patients reported TEAEs, which included headache (24.0%), abdominal pain (12.0%), nasopharyngitis (12.0%), pharyngitis (12.0%), sinusitis (12.0%), bronchitis (8.0%), upper respiratory tract infection (8.0%), and insomnia (8.0%); 61.5% experienced a TEAE with placebo.
Dexlansoprazole is safe and efficacious for healing EE and maintenance of healed EE in adolescents.
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498–547. CrossRef
Sherman PM, Hassall E, Fagundes-Neto U, et al. A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol. 2009;104:1278–1295. (quiz 1296). CrossRef
Nwokediuko SC. Current trends in the management of gastroesophageal reflux disease: a review. ISRN Gastroenterol. 2012;2012:391631. CrossRef
Guimaraes EV, Guerra PV, Penna FJ. Management of gastroesophageal reflux disease and erosive esophagitis in pediatric patients: focus on delayed-release esomeprazole. Ther Clin Risk Manag. 2010;6:531–537. CrossRef
Cezard JP. Managing gastro-oesophageal reflux disease in children. Digestion. 2004;69:3–8. CrossRef
Nelson SP, Chen EH, Syniar GM, Christoffel KK, Pediatric Practice Research Group. Prevalence of symptoms of gastroesophageal reflux during childhood: a pediatric practice-based survey. Arch Pediatr Adolesc Med. 2000;154:150–154. CrossRef
Gilger MA, El-Serag HB, Gold BD, et al. Prevalence of endoscopic findings of erosive esophagitis in children: a population-based study. J Pediatr Gastroenterol Nutr. 2008;47:141–146. CrossRef
Gunasekaran TS, Hassall EG. Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr. 1993;123:148–154. CrossRef
Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. J Pediatr. 2000;137:800–807. CrossRef
Tolia V, Ferry G, Gunasekaran T, Huang B, Keith R, Book L. Efficacy of lansoprazole in the treatment of gastroesophageal reflux disease in children. J Pediatr Gastroenterol Nutr. 2002;35:S308–S318. CrossRef
Tolia V, Bishop PR, Tsou VM, et al. Multicenter, randomized, double-blind study comparing 10, 20 and 40 mg pantoprazole in children (5–11 years) with symptomatic gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2006;42:384–391. CrossRef
Gilger MA, Tolia V, Vandenplas Y, Youssef NN, Traxler B, Illueca M. Safety and tolerability of esomeprazole in children with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2008;46:524–533. PubMed
Fiedorek S, Tolia V, Gold BD, et al. Efficacy and safety of lansoprazole in adolescents with symptomatic erosive and non-erosive gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2005;40:319–327. CrossRef
Haddad I, Kierkus J, Tron E, et al. Maintenance of efficacy and safety of rabeprazole in children with endoscopically proven GERD. J Pediatr Gastroenterol Nutr. 2014;58:510–517. CrossRef
Boccia G, Manguso F, Miele E, Buonavolonta R, Staiano A. Maintenance therapy for erosive esophagitis in children after healing by omeprazole: is it advisable? Am J Gastroenterol. 2007;102:1291–1297. CrossRef
Hassall E, Shepherd R, Koletzko S, Radke M, Henderson C, Lundborg P. Long-term maintenance treatment with omeprazole in children with healed erosive oesophagitis: a prospective study. Aliment Pharmacol Ther. 2012;35:368–379. CrossRef
Takeda. Dexilant (dexlansoprazole) [package insert]. Deerfield: Takeda Pharmaceuticals America, Inc.; 2016.
Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel Dual Delayed Release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009;25:627–638. CrossRef
Frye JW, Peura DA. Managing gastroesophageal reflux disease—comparative efficacy and outcomes of dexlansoprazole MR. Ther Clin Risk Manag. 2015;11:1649–1656. CrossRef
Sharma P, Shaheen NJ, Perez MC, et al. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation—results from two randomized controlled studies. Aliment Pharmacol Ther. 2009;29:731–741. CrossRef
Metz DC, Howden CW, Perez MC, Larsen L, O’Neil J, Atkinson SN. Clinical trial: dexlansoprazole MR, a proton pump inhibitor with dual delayed-release technology, effectively controls symptoms and prevents relapse in patients with healed erosive oesophagitis. Aliment Pharmacol Ther. 2009;29:742–754. CrossRef
Kukulka M, Wu J, Perez MC. Pharmacokinetics and safety of dexlansoprazole MR in adolescents with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2012;54:41–47. CrossRef
El-Serag HB, Richardson P, Pilgrim P, Gilger MA. Determinants of gastroesophageal reflux disease in adults with a history of childhood gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2007;5:696–701. CrossRef
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–2194. CrossRef
International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonized tripartite guideline: guideline for Good Clinical Practice. J Postgrad Med. 2001;47:45–50.
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45:172–180. CrossRef
Brown EG, Wood L, Wood S. The medical dictionary for regulatory activities (MedDRA). Drug Saf. 1999;20:109–117. CrossRef
Gold BD, Freston JW. Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment. Paediatr Drugs. 2002;4:673–685. CrossRef
Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308–328. (quiz 329). CrossRef
Peura DA, Metz DC, Dabholkar AH, Paris MM, Yu P, Atkinson SN. Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience. Aliment Pharmacol Ther. 2009;30:1010–1021. CrossRef
Vandenplas Y, Hauser B. An updated review on gastro-esophageal reflux in pediatrics. Expert Rev Gastroenterol Hepatol. 2015;9:1511–1521. CrossRef
Gold BD. Review article: epidemiology and management of gastro-oesophageal reflux in children. Aliment Pharmacol Ther. 2004;19:22–27. CrossRef
- Dual Delayed-Release Dexlansoprazole for Healing and Maintenance of Healed Erosive Esophagitis: A Safety Study in Adolescents
Benjamin D. Gold
Maria Claudia Perez
- Springer US
Digestive Diseases and Sciences
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
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