2018 Section 6 - Laryngology, Voice Disorders, and Bronchoesophalogy

Reprinted by permission of Aliment Pharmacol Ther. 2015; 41(11):1162-1174.

Alimentary Pharmacology and Therapeutics

Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies S. E. Attwood*, C. Ell † , J. P. Galmiche § , R. Fiocca ¶ , J. G. Hatlebakk**, B. Hasselgren †† , G. Langstr € om †† , M. Jahreskog †† , S. Eklund †† , T. Lind †† & L. Lundell ‡‡

SUMMARY

*North Tyneside General Hospital, North Shields, UK. † Sana Klinikum Offenbach, Frankfurt, Germany. § H ^ otel Dieu-CHU de Nantes, Nantes, France. ¶ University of Genoa and IRCCS S. Martino, Genoa, Italy. **Haukeland University Hospital, Bergen, Norway. †† AstraZeneca R&D, M € olndal, Sweden. ‡‡ Department of Surgery, Centre for Digestive Diseases, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Correspondence to: Prof. S. E. Attwood, Department of Surgery, North Tyneside General Hospital, North Shields, UK. E-mail: stephen.attwood@nhct.nhs.uk

Background Control of chronic gastro-oesophageal re fl ux disease may be achieved either by anti-re fl ux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary ef fi cacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby pro- vide a valid scienti fi c platform for assessing long-term PPI safety. Aim To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies. Methods Safety data were collected from patients during the 12-year period of the SOPRAN study ( n = 298) and the 5-year period of the LOTUS study ( n = 514). Reported serious adverse events (SAEs) and changes in labora- tory variables were analysed. Results Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B 12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the fi rst year. Conclusion No major safety concerns arose during 5 – 12 years of continuous PPI ther- apy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

Publication data Submitted 30 September 2014 First decision 17 October 2014 Resubmitted 16 March 2015 Accepted 19 March 2015 EV Pub Online 10 April 2015

This article was accepted for publication after full peer-review.

Aliment Pharmacol Ther 2015; 41: 1162 – 1174

ª 2015 John Wiley & Sons Ltd doi:10.1111/apt.13194

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