Observational cohort study: safety outcomes in children using proton pump inhibitors or histamine-2 receptor antagonists

Abstract

Objective: Acid suppression with histamine-2 receptor antagonists (H₂RAs) or proton pump inhibitors (PPIs) is recommended for children with persistent gastroesophageal reflux disease symptoms. In this retrospective, observational postauthorization study, we aimed to assess and compare safety outcomes in pediatric first-time users of esomeprazole, other PPIs or H₂RAs.

Methods: Data on children (aged 0–18 years) first dispensed esomeprazole, other PPIs or H₂RAs between September 2008 and August 2011 was obtained from the Dutch PHARMO Database Network. Hospitalizations for seven predefined safety outcomes were evaluated (maximum follow-up: 18 months). Rate ratios were calculated using Poisson regression adjusted for baseline imbalances. Discharge letters were reviewed for event occurrence confirmation.

Results: Of 23,470 included children, 2820 (median age: 3 years) were prescribed esomeprazole, 13,818 (median age: 15 years) other PPIs and 6832 (median age: 5 years) H₂RAs. In total, 504 (2%) children were hospitalized for 762 predefined events: gastroenteritis (246); convulsion/seizure (200); pneumonia (154); failure to thrive (119); acute interstitial nephritis (19); thrombocytopenia (23); and angioneurotic edema (1). Significant differences between cohorts were observed only for failure to thrive, with adjusted rate ratios (95% confidence interval) for esomeprazole of 6.1 (2.4–15.7) vs. other PPIs and 6.1 (2.9–12.8) vs. H₂RAs among current users. Occurrence was confirmed for 74% of assessable events. Confirmation rates were highest for pneumonia (81%) and lowest for failure to thrive (40%).

Conclusions: Hospitalization rates for predefined outcomes were low and mostly similar in pediatric first-time users of PPIs and of H₂RAs.

Trial registration: NCT01338363.

Keywords:

• Proton pump inhibitor
• histamine receptor antagonist
• safety events
• children

Transparency

Declaration of funding

This work was supported by AstraZeneca Gothenburg, Sweden.

Author contributions: E.H. contributed to the conception or design of the work, data collection, data analysis, data interpretation, drafting of the article and critical revision of the article. S.J. contributed to the conception or design of the work, data interpretation and critical revision of the article. P.N. contributed to the conception or design of the work, data interpretation and critical revision of the article. F.J.A.P.-v.B. contributed to the conception or design of the work, data analysis, data interpretation, drafting of the article and critical revision of the article. E.J.K. contributed to the conception or design of the work, assessment of blinded case records, codrafting of the article and critical revision of the article. R.M.C.H. contributed to the conception or design of the work, data interpretation and critical revision of the article.

Declaration of financial/other relationships

E.H., F.J.A.P.-v.B. and R.M.C.H. have disclosed that they are employed by the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for government and related healthcare authorities and several pharmaceutical companies. S.J. has disclosed that she is an employee of AstraZeneca. P.N. has disclosed that he was an employee of AstraZeneca at the time the study was conducted. E.J.K. has disclosed that he has received speaker’s fees from AstraZeneca.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

Writing support was provided by Dr. Anja Becher of Oxford PharmaGenesis, Oxford, UK, and was funded by AstraZeneca Gothenburg, Sweden.