Long‐term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the <scp>SOPRAN</scp> and <scp>LOTUS</scp> studies

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Control of chronic gastro‐oesophageal reflux disease may be achieved either by anti‐reflux surgery (<jats:styled-content style="fixed-case">ARS</jats:styled-content>) or by long‐term medical therapy with proton pump inhibitors (<jats:styled-content style="fixed-case">PPI</jats:styled-content>s). The primary efficacy results of the <jats:styled-content style="fixed-case">SOPRAN</jats:styled-content> study, comparing long‐term omeprazole use with open <jats:styled-content style="fixed-case">ARS</jats:styled-content>, and the <jats:styled-content style="fixed-case">LOTUS</jats:styled-content> study, comparing long‐term esomeprazole use with laparoscopic <jats:styled-content style="fixed-case">ARS</jats:styled-content>, have been reported. A secondary objective of these studies was to address the long‐term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long‐term <jats:styled-content style="fixed-case">PPI</jats:styled-content> safety.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To assess the safety of long‐term <jats:styled-content style="fixed-case">PPI</jats:styled-content> therapy with omeprazole and esomeprazole through analyses of data from the randomised <jats:styled-content style="fixed-case">SOPRAN</jats:styled-content> and <jats:styled-content style="fixed-case">LOTUS</jats:styled-content> studies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Safety data were collected from patients during the 12‐year period of the <jats:styled-content style="fixed-case">SOPRAN</jats:styled-content> study (<jats:italic>n </jats:italic>=<jats:italic> </jats:italic>298) and the 5‐year period of the <jats:styled-content style="fixed-case">LOTUS</jats:styled-content> study (<jats:italic>n </jats:italic>=<jats:italic> </jats:italic>514). Reported serious adverse events (<jats:styled-content style="fixed-case">SAE</jats:styled-content>s) and changes in laboratory variables were analysed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Across both studies, <jats:styled-content style="fixed-case">SAE</jats:styled-content>s were reported at a similar frequency in the <jats:styled-content style="fixed-case">PPI</jats:styled-content> and <jats:styled-content style="fixed-case">ARS</jats:styled-content> treatment groups. Taking the time frames into consideration, the number of fatal <jats:styled-content style="fixed-case">SAE</jats:styled-content>s 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<jats:sub>12</jats:sub>, folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the <jats:styled-content style="fixed-case">PPI</jats:styled-content> groups, with the greatest increases observed in the first year.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>No major safety concerns arose during 5–12 years of continuous <jats:styled-content style="fixed-case">PPI</jats:styled-content> therapy. (ClinicalTrials.gov: <jats:styled-content style="fixed-case">NCT</jats:styled-content>00251927 and <jats:styled-content style="fixed-case">NCT</jats:styled-content>00256737).</jats:p></jats:sec>