2018 Section 6 - Laryngology, Voice Disorders, and Bronchoesophalogy

Long-term safety of PPI therapy

tion of patients in the ARS and PPI groups during the SOPRAN study (at 5 years: 50% and 42% respectively; at 12 years: 63% and 54% respectively) and the LOTUS study (at 5 years: 29% and 24% respectively). In the SOPRAN study, there were 17 (11%) and 8 (6%) patients who experienced an SAE leading to death in the omeprazole and open ARS groups during the 12- year study period respectively. In the LOTUS study, three patients had an SAE leading to death during 5 years, all of which were in the esomeprazole group. Two additional SAEs (one in each treatment group) were reported during the LOTUS study that led to deaths after study termination. 10 None of the fatal SAEs observed were considered by the investigator to be related to study treatment. Infections Overall, infections and infestations [System Organ Class (SOC) according to MedDRA] were reported as SAEs numerically more frequently in patients in the open ARS group than in the omeprazole group in the SOPRAN study (14% and 10% respectively), and more so in the esomeprazole group than the laparoscopic ARS group in the LOTUS study (4% and 2% respectively). With regard to enteric infections, in the SOPRAN study, there were two SAEs with diarrhoea (which might indicate enteric infection); one in each treatment group. In addition, two SAEs of gastroenteritis and one SAE of Salmonella infection were reported in the open ARS group and one SAE of gastroenteritis and one SAE of Salmonella infection were reported in the omeprazole group. In the LOTUS study, there were three gastroenteritis SAEs reported in the esomeprazole group and one in the laparoscopic ARS group, but no SAEs of diarrhoea in any of the treatment arms. When looking at GSRS data (not SAEs), there were no differences in diarrhoea item scores between the PPI and ARS groups in either study after up to 10 years (SOPRAN) and 5 years (LOTUS) of scoring (data not shown). Pneumonia was reported as an SAE in four patients in the open ARS group and in three patients in the omeprazole group in the SOPRAN study. In the LOTUS study, three patients had pneumonia in the esomeprazole group (one case, in a man aged 64 years, had a fatal out- come) and one patient had pneumonia in the laparo- scopic ARS group. In addition, it should be noted that there were three pneumonia cases coded as post-proce- SAFETY TOPICS HIGHLIGHTED IN THE LITERATURE

total exposure time was 1046 years for the laparoscopic ARS group (post-surgery) and 1067 years for the esomeprazole group (on PPI treatment). The total study time was therefore 2% greater in the esomeprazole group than in the laparoscopic ARS group. Patient characteristics In the SOPRAN study, 155 patients (median age: 50 years; 77% men) were randomised to open ARS, of whom 11 (7%) withdrew before surgery, leaving 144 patients in the open ARS group; 155 patients (median age: 54 years; 75% men) were randomised to omeprazole therapy, of whom 1 (0.6%) withdrew before treatment, leaving 154 patients in the omeprazole group. The pro- portion of smokers was 25% and 21% and of alcohol users was 68% and 70%, in the ARS group and the omeprazole group respectively. The proportion of patients who were H. pylori -positive was 29% in the ARS group and 20% in the omeprazole group. In the LOTUS study, 288 patients (median age: 44 years; 69% men) were randomised to laparoscopic ARS, of whom 40 (14%) withdrew before surgery, leav- ing 248 patients in the laparoscopic ARS group. No patients withdrew prior to treatment in the esomeprazole group which comprised 266 patients (median age: 46 years; 75% men). The proportion of smokers was 28% and 22% and of alcohol users was 58% and 66%, in the laparoscopic ARS group and the esomeprazole group respectively. The proportion of patients who were H. pylori -positive was 10% in the laparoscopic ARS group and 14% in the esomeprazole group. General safety data Laboratory assessments. There were no unexpected dif- ferences in laboratory values between the PPI and ARS groups in either study, and no clinically signi fi cant changes over time were identi fi ed [Table 1 (median val- ues) and Figures 1 – 4 (individual values)]. Nonserious adverse events. Nonserious AEs (collected during the fi rst 5 years of the SOPRAN study only) were consistent with the overall known safety pro fi le of omep- razole and did not raise any safety concerns. These data are not within the scope of the current study questions and are thus not presented here. Serious adverse events. The most commonly reported SAEs in the SOPRAN study are summarised in Table 2 and corresponding data for the LOTUS study are presented in Table 3. SAEs occurred in a similar propor-

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

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