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Safety and Efficacy of Long Term Esomeprazole Therapy in Patients with Healed Erosive Oesophagitis

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Abstract

Objective: To evaluate the safety and tolerability of long term treatment with esomeprazole in patients with healed erosive oesophagitis, and to describe its efficacy in the maintenance of healing.

Design and setting: US multicentre, noncomparative, nonblind study.

Patients and participants: 807 patients with endoscopically confirmed healed erosive oesophagitis.

Methods: Patients received esomeprazole 40mg once daily for up to 12 months. Adverse events and clinical laboratory tests were assessed over the study period. Endoscopy was performed at the final visit of the antecedent healing trials and at months 6 and 12 of the current safety trial; gastric biopsies were obtained at the initial visit of the healing trials and at the end of the safety trial.

Results: 80.9% of patients completed 6 months of treatment; 76.6% completed 12 months of treatment. There were no serious drug-related adverse events. Diarrhoea, abdominal pain, flatulence, and headache were the only treatment-related adverse events reported by >3% of patients. Mean changes in laboratory measures were generally small and not clinically meaningful. Plasma gastrin levels increased, as expected, and reached a plateau after 3 months. No changes in gastric histological scores were noted in the majority of patients. Evaluation of gastric biopsies revealed an overall decline in chronic inflammation and atrophy. Intestinal metaplasia findings remained essentially unchanged. Life table estimates of maintenance of healing were 93.7% [95% confidence interval (CI) 92.0 to 95.5%] at 6 months and 89.4% (95% CI 87.0 to 91.7%) at 12 months.

Conclusions: Daily treatment with esomeprazole 40mg for up to 1 year in patients with healed erosive oesophagitis was generally well tolerated and effective. No safety concerns arose.

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References

  1. Chiba N. Proton pump inhibitors in acute healing and maintenance of erosive or worse esophagitis: a systematic overview. Can J Gastroenterol 1997; 11Suppl. B: 66B–73B

    PubMed  Google Scholar 

  2. De Vault KR, Castell DO. Current diagnosis and treatment of gastroesophageal reflux disease. Mayo Clin Proc 1994; 69: 867–76

    Google Scholar 

  3. Maton PN. Omeprazole. N Engl J Med 1991; 324: 965–75

    Article  PubMed  CAS  Google Scholar 

  4. Bordi C, Cocconi G, Togni R, et al. Gastric endocrine cell proliferation; association with Zollinger-Ellison syndrome. Arch Pathol 1974; 98: 274–8

    PubMed  CAS  Google Scholar 

  5. Carney JA, Go VL, Fairbanks VF, et al. FE. The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy. Ann Intern Med 1983; 99: 761–6

    PubMed  CAS  Google Scholar 

  6. Borch K, Renvall H, Liedberg G. Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia. Gastroenterology 1985; 88: 638–48

    PubMed  CAS  Google Scholar 

  7. Solcia E, Capella C, Fiocca R, et al. Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia; a newly recognized association. Am J Surg Pathol 1990; 14: 503–13

    Article  PubMed  CAS  Google Scholar 

  8. Johnson LR, Guthrie PD. Mucosal DNA synthesis: a short term index of the trophic action of gastrin. Gastroenterology 1974; 67: 453–9

    PubMed  CAS  Google Scholar 

  9. Solomon TE. Trophic effects of pentagastrin on gastrointestinal tract in fed and fasted rats. Gastroenterology 1986; 91: 108–6

    PubMed  CAS  Google Scholar 

  10. Steinberg WM, King CE, Toskes PP. Malabsorption of prote-inbound cobalamin but not unbound cobalamin during cimetidine administration. Dig Dis Sci 1980; 25: 188–91

    Article  PubMed  CAS  Google Scholar 

  11. Koop H, Bachem MG. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol 1992; 14: 288–92

    Article  PubMed  CAS  Google Scholar 

  12. Koop H. Review article: metabolic consequences of long-term inhibition of acid secretion by omeprazole. Aliment Pharmacol Ther 1992; 6: 399–406

    Article  PubMed  CAS  Google Scholar 

  13. Langtry HD, Wilde MI. Omeprazole: a review of its use in Helicobacter pylori infection, gastro-oesophageal reflux disease and peptic ulcers induced by nonsteroidal anti-inflammatory drugs. Drugs 1998; 56: 447–86

    Article  PubMed  CAS  Google Scholar 

  14. Lundell L, Miettinen P, Myrvold HE, et al. Lack of effect of acid suppression therapy on gastric atrophy. Nordic Gerd Study Group. Gastroenterology 1999; 117: 319–26

    Article  PubMed  CAS  Google Scholar 

  15. Laine L, Ahnen D, McClain C, et al. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther 2000; 14: 651–8

    Article  PubMed  CAS  Google Scholar 

  16. Lind T, Rydberg L, Kylebäck A, et al. Esomeprazole provides improved acid control versus omeprazole in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000; 14: 861–67

    Article  PubMed  CAS  Google Scholar 

  17. Röhss K, Claar-Nilsson C, Lundin C, et al. Esomeprazole 40 mg provides more effective acid control than lansoprazole 30 mg. Am J Gastroenterol 2000; 95(9): 2432–3

    Google Scholar 

  18. Wilder-Smith C, Röhss K, Claar-Nilsson C, et al. Esomeprazole 40 mg provides more effective acid control than rabeprazole 20 mg [abstract]. Gut 2000; 47Suppl. III: A63

    Google Scholar 

  19. Kahrilas PJ, Falk GW, Johnson DA, et al. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomised controlled trial. Aliment Pharmacol Ther 2000; 14: 1249–58

    Article  PubMed  CAS  Google Scholar 

  20. Richter JE, Kahrilas PJ, Johanson J, et al. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am J Gastroenterol 2001; 96: 656–65

    Article  PubMed  CAS  Google Scholar 

  21. Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis; the updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996; 20: 1161–81

    Article  PubMed  CAS  Google Scholar 

  22. Price AB. The Sydney System: histological division. J Gastroenterol Hepatol 1991; 6: 209–2

    Article  PubMed  CAS  Google Scholar 

  23. Solcia E, Bordi C, Creutzfeldt W, et al. Histopathological classification of nonantral gastric endocrine growths in man. Digestion 1988; 41: 185–200

    Article  PubMed  CAS  Google Scholar 

  24. Solcia E, Fiocca R, Villani L, et al. Hyperplastic, dysplastic, and neoplastic enterochromafin-like cell proliferation of the gastric mucosa. Classification and histogenesis. Am J Surg Pathol 1995; 19Suppl. 1: S1–7

    PubMed  Google Scholar 

  25. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45: 172–80

    Article  PubMed  CAS  Google Scholar 

  26. Armstrong D, Bennett JR, Blum AL, et al. The endoscopic assessment of esophagitis: a progress report on observer agreement. Gastroenterology 1996; 111: 85–92

    Article  PubMed  CAS  Google Scholar 

  27. Akiyama J, Matsueda K, Shoda R, et al. A new endoscopic criteria for diagnosing mild reflux esophagitis: significance of decreased vascularity around the esophagogastric junction. Gastroenterology 1999; 116: A110

    Google Scholar 

  28. Cremer M, Janssens J, Laruelle N. Comparison of the two reflux oesophagitis classifications: ‘Savary Miller’ and ‘Los Angeles’ for low grade oesophagitis. Acta Gastroenterol Belg 1998; 61: C43

    Google Scholar 

  29. Kusano M, Ino K, Yamada T, et al. Interobserver and intraobserver variation in endoscopic assessment of GERD using the ‘Los Angeles’ classification. Gastrointest Endosc 1999; 49: 700–4

    Article  PubMed  CAS  Google Scholar 

  30. Genta RM, Magner DJ, D’Amico D, et al. Safety of long-term treatment with a new PPI, esomeprazole in GERD patients [abstract]. Gastroenterology 2000; 118: A16

    Article  Google Scholar 

  31. Vakil N, Shaker R, Johnson DA, et al. The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive esophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety. Aliment Pharmacol Ther. In press

  32. Johnson DA, Benjamin SB, Vakil NB, et al. Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety. Am J Gastroenterol 2001; 96: 27–34

    Article  PubMed  CAS  Google Scholar 

  33. Klinkenberg-Knol EC, Festen HP, Jansen JB, et al. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med 1994; 121: 161–7

    PubMed  CAS  Google Scholar 

  34. Hetzel DJ, Dent J, Reed WD, et al. Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology 1988; 95: 903–12

    PubMed  CAS  Google Scholar 

  35. Freston JW. Long-term acid control and proton pump inhibitors: interactions and safety issues in perspective. Am J Gastroenterol 1997; 92: 51S–57S

    PubMed  CAS  Google Scholar 

  36. Koop H, Eissele R. Reduction of gastric acid secretion: pathophysiologic and clinically relevant sequelae. Z Gastroenterol 1991; 29: 613–7

    PubMed  CAS  Google Scholar 

  37. Arnold R. Safety of proton pump inhibitors; an overview. Aliment Pharmacol Ther 1994; 8: 65–70

    PubMed  Google Scholar 

  38. Waldum HL, Arnestad JS, Brenna E, et al. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut 1996; 39: 649–53

    Article  PubMed  CAS  Google Scholar 

  39. Howden CW. Vitamin B12 levels during prolonged treatment with proton pump inhibitors. J Clin Gastroenterol 1999; 30: 29–33

    Article  Google Scholar 

  40. Schenk BE, Festen HP, Kuipers EJ, et al. Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin. Aliment Pharmacol Ther 1996; 10: 541–54

    Article  PubMed  CAS  Google Scholar 

  41. Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med 1998; 104: 422–30

    Article  PubMed  CAS  Google Scholar 

  42. Walan A, Havu N, Lundell L, et al. Vitamin B12 levels during long-term treatment with omeprazole or after anti-reflux therapy in patients with GERD. Results of a randomized study. Gastroenterology 2000; 118: A219

    Article  Google Scholar 

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Acknowledgements

Both Paul N. Maton and Nimish B. Vakil have acted as consultants to AstraZeneca. This manuscript was prepared with the assistance of Eileen Gallagher and resources from AstraZeneca.

An abstract of this study was presented at Digestive Disease Week 2000 in San Diego, CA, May 21–24.

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Authors and Affiliations

  1. Digestive Diseases Research Institute, 3435 NW 56th Street, Suite 206, Oklahoma City, Oklahoma, 73112, USA

    Paul N. Maton

  2. University of Wisconsin Medical School, Milwaukee, Wisconsin, USA

    Nimish B. Vakil

  3. AstraZeneca LP, Wayne, Pennsylvania, USA

    Jeffrey G. Levine, Clara Hwang & Wendy Skammer

  4. AstraZeneca, Mölndal, Sweden

    Per Lundborg

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  1. Paul N. Maton
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  2. Nimish B. Vakil
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  4. Clara Hwang
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  6. Per Lundborg
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Maton, P.N., Vakil, N.B., Levine, J.G. et al. Safety and Efficacy of Long Term Esomeprazole Therapy in Patients with Healed Erosive Oesophagitis. Drug-Safety 24, 625–635 (2001). https://doi.org/10.2165/00002018-200124080-00006

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