2018 Section 6 - Laryngology, Voice Disorders, and Bronchoesophalogy

Long-term safety of PPI therapy

Epidemiological studies on a possible association between PPI therapy and community-acquired pneumo- nia have so far produced con fl icting results. A Dutch database 29 indicated an 80 – 90% increase in community- acquired pneumonia in patients with current vs. past use of PPIs and results from a database in Denmark 30 indicated a 50% increase in the risk of hospitalisation for community-acquired pneumonia in current PPI users. In contrast, the UK General Practice Database 31 and the US Group Health database 32 did not show an association between current PPI use and community- acquired pneumonia. Based on the incidence and preva- lence fi gures from the former studies, it could be expected that at least a trend would emerge towards a difference between the current PPI arms as compared to the ARS-operated patients. However, the number of pneumonia events was basically identical in the respec- tive study groups in both the SOPRAN and the LOTUS study. This is consistent with a recently performed pooled analysis of placebo-controlled studies comprising 9877 patients treated with esomeprazole and 2982 patients treated with omeprazole, showing no differ- ences between active and placebo treatment concerning lower respiratory tract infections. 33 In the LOTUS study, events in the SOC ‘ benign, malignant and unspeci fi ed neoplasms (including cysts and polyps) ’ were reported more frequently in the PPI-treated patients than in those having ARS. In these situations, it is of critical importance to carefully scrutinise each individual case to screen for a potential signal of concern, not least because of the small num- ber of events and the signi fi cant variety of background factors. The data were carefully reviewed and evaluated during the study by internal and external experts including the Steering Committee and an Advisory Board and it was concluded that they did not raise any safety concerns. CONCLUSIONS No major safety concerns were identi fi ed during 5 – 12 years of continuous PPI therapy with esomeprazole and omeprazole. AUTHORSHIP Guarantor of the article : S. E. Attwood (LOTUS data) and Lars Lundell (SOPRAN and LOTUS data).

Author contributions : Stephen Attwood, Lars Lundell and Tore Lind took a lead in determining the study con- cept and design, analysing and interpreting the data, as well as drafting and critically reviewing the manuscript for important clinical and intellectual content. G € oran Langstr € om performed the statistical analysis and criti- cally reviewed the manuscript drafts. Jan Hatlebakk, Christian Ell, Jean-Paul Galmiche and Roberto Fiocca had a major role in determining the study concept and design, analysing and interpreting the data, as well as drafting and critically reviewing the manuscript for important clinical and intellectual content. Stefan Ekl- und, Birgitta Hasselgren and Marianne Jahreskog had a major role in analysing and interpreting the data, as well as drafting and critically reviewing the manuscript for important clinical and intellectual content. All authors have approved the fi nal draft of the manu- script, including the authorship list. ACKNOWLEDGEMENTS Declaration of personal interests: Writing support was provided by Michael Molloy-Bland and Madeline Frame. Michael Molloy-Bland is an employee of Oxford Phar- maGenesis TM Ltd, Oxford, UK, which received funding from AstraZeneca R&D, M € olndal, Sweden. Madeline Frame was employed by AstraZeneca R&D, M € olndal, Sweden at the time the study was conducted. Tore Lind is a consultant and former employee of AstraZeneca R&D, M € olndal, Sweden. Stefan Eklund, G € oran Langstr € om, Birgitta Hasselgren and Marianne Jahreskog- are employed by AstraZeneca R&D, M € olndal, Sweden. Lars Lundell is a member of the steering committee for LOTUS and has no other con fl icts to declare. Jean-Paul Galmiche is a consultant for AstraZeneca, MKT, Shire and Given Imaging. He has prepared educational presen- tations for Shire Movetis. Stephen Attwood has been a consultant speaker for AstraZeneca and Ethicon Endo- surgery, and has been a member of the steering commit- tee for LOTUS. Christian Ell receives grants for research from several biomedical companies (AstraZeneca, Fuji- non, Erbe, and Hitachi). Roberto Fiocca has received tra- vel and related expenses for attending study-associated meetings and his institution received a grant from Astra- Zeneca for central histological analyses. Declaration of funding interests : This study was funded by AstraZeneca R&D, M € olndal, Sweden.

Aliment Pharmacol Ther 2015; 41: 1162 – 1174 ª 2015 John Wiley & Sons Ltd

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