Skip to main content

Advertisement

SpringerLink
Log in

Maintenance therapy of gastroesophageal reflux disease

  • Clinical Review
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

The aims of treatment of gastroesophageal reflux disease (GERD) are to cure mucosal breaks, control symptoms, and prevent complications (e.g. stricture, Barrett’s esophagus, and esophageal adenocarcinoma). Proton pump inhibitors (PPIs) are known to be the best drugs to cure esophagitis; however, a highrecurrence rate of about 80% was described after the completion of initial therapy. Regretfully, not so many physicians perform maintenance therapy in clinical practice. Histamine H2 receptor antagonists have an insufficient effect in maintenance therapy compared with PPIs; therefore, they could be prescribed for mild reflux esophagitis. Several clinical trials have been conducted to investigate the efficacy of continuous PPI administration maintenance therapy for GERD. Among these trials, recent large-scale studies showed that esomeprazole was equal to or superior to other kinds of PPIs. On the other hand, on-demand PPI studies have been conducted, mainly in patients with nonerosive reflux disease or uninvestigated GERD;however, this strategy was less effective than continuous therapy in many studies. Because on-demand therapy is less expensive, it is worth confirming this strategy in further studies. Studies of maintenance therapy with investigations conducted for as long a period as 5 years have described that PPI maintenance therapy could be considered as effective, safe, and well tolerated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global consensus group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–20.

    Article  PubMed  Google Scholar 

  2. Sugiyama T, Nishikawa K, Komatsu Y, Ishizuka J, Mizushima T, Kumagai A, et al. Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers? Dig Dis Sci. 2001;46:307–10.

    Article  CAS  PubMed  Google Scholar 

  3. Kinoshita Y, Kawanami C, Kishi K, Nakata H, Seino Y, Chiba T. Helicobacter pylori independent chronological change in gastric acid secretion in the Japanese. Gut. 1997;41:452–8.

    CAS  PubMed  Google Scholar 

  4. Miwa H, Oshima T, Tomita T, Kim Y, Hori K, Matsumoto T. Gastro-esophageal reflux disease: the recent trend in Japan. Clin J Gastroenterol. 2008;1:133–8.

    Article  Google Scholar 

  5. Watanabe S, Hojo M, Nagahara A. Metabolic syndrome and gastrointestinal diseases. J Gastroenterol. 2007;42:267–74.

    Article  PubMed  Google Scholar 

  6. Furukawa N, Iwakiri R, Koyama T, Okamoto K, Yoshida T, Kashiwagi Y, et al. Proportion of reflux esophagitis in 6010 Japanese adults: prospective evaluation by endoscopy. J Gastroenterol. 1999;34:441–4.

    Article  CAS  PubMed  Google Scholar 

  7. Yamaguchi T, Sugimoto T, Yamada H, Kanzawa M, Yano S, Yamauchi M, et al. The presence and severity of vertebral fractures is associated with the presence of esophageal hiatal hernia in postmenopausal women. Osteoporos Int. 2002;13:331–6.

    Article  CAS  PubMed  Google Scholar 

  8. Yoshimura M, Nagahara A, Ohtaka K, Shimada Y, Asaoka D, Kurosawa A, et al. Presence of vertebral fractures is highly associated with hiatal hernia and reflux esophagitis in Japanese elderly people. Intern Med. 2008;47:1451–5.

    Article  PubMed  Google Scholar 

  9. Iwakiri K. The role of excessive esophageal acid exposure in patients with gastroesophageal reflux disease. Clin J Gastroenterol. 2009;2:371–9.

    Article  Google Scholar 

  10. Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44:518–34.

    Article  PubMed  Google Scholar 

  11. Armstrong D. Systematic review: persistence and severity in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2008;28:841–53.

    CAS  PubMed  Google Scholar 

  12. Fass R. Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol. 2007;41:131–7.

    Article  PubMed  Google Scholar 

  13. Fass R. Epidemiology and pathophysiology of symptomatic gastroesophageal reflux disease. Am J Gastroenterol. 2003;98(3 Suppl):S2–7.

    Article  PubMed  Google Scholar 

  14. Fujiwara Y, Higuchi K, Shiba M, Yamamori K, Watanabe Y, Sasaki E, et al. Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan. Am J Gastroenterol. 2005;100:754–8.

    Article  PubMed  Google Scholar 

  15. Miwa H, Minoo T, Hojo M, Yaginuma R, Nagahara A, Kawabe M, et al. Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases. Aliment Pharmacol Ther. 2004;20(Suppl 1):112–7.

    Article  PubMed  Google Scholar 

  16. Nagahara A, Miwa H, Minoo T, Hojo M, Kawabe M, Osada T, et al. Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease. J Clin Gastroenterol. 2006;40:891–5.

    Article  CAS  PubMed  Google Scholar 

  17. Carlsson R, Galmiche JP, Dent J, Lundell L, Frison L. Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: a meta-analysis of long-term omeprazole trials. Aliment Pharmacol Ther. 1997;11:473–82.

    Article  CAS  PubMed  Google Scholar 

  18. Wong WM, Lim P, Wong BC. Clinical practice pattern of gastroenterologists, primary care physicians, and otolaryngologists for the management of GERD in the Asia-Pacific region: the FAST survey. J Gastroenterol Hepatol. 2004;19(Suppl 3):S54–60.

    Article  PubMed  Google Scholar 

  19. Simon TJ, Roberts WG, Berlin RG, Hayden LJ, Berman RS, Reagan JE. Acid suppression by famotidine 20 mg twice daily or 40 mg twice daily in preventing relapse of endoscopic recurrence of erosive esophagitis. Clin Ther. 1995;17:1147–56.

    Article  CAS  PubMed  Google Scholar 

  20. Mine S, Iida T, Tabata T, Kishikawa H, Tanaka Y. Management of symptoms in step-down therapy of gastroesophageal reflux disease. J Gastroenterol Hepatol. 2005;20:1365–70.

    Article  CAS  PubMed  Google Scholar 

  21. Tytgat GN. Possibilities and shortcomings of maintenance therapy in gastroesophageal reflux disease. Dig Surg. 1999;16:1–6.

    Article  CAS  PubMed  Google Scholar 

  22. Festen HP, Schenk E, Tan G, Snel P, Nelis F. Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease: short- and long-term treatment. The Dutch Reflux Study Group. Am J Gastroenterol. 1999;94:931–6.

    Article  CAS  PubMed  Google Scholar 

  23. Bardhan KD, Müller-Lissner S, Bigard MA, Bianchi Porro G, Ponce J, Hosie J, et al. Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group. BMJ. 1999;318:502–7.

    CAS  PubMed  Google Scholar 

  24. Talley NJ, Moore MG, Sprogis A, Katelaris P. Randomised controlled trial of pantoprazole versus ranitidine for the treatment of uninvestigated heartburn in primary care. Med J Aust. 2002;177:423–7.

    PubMed  Google Scholar 

  25. Laursen LS, Havelund T, Bondesen S, Hansen J, Sanchez G, Sebelin E, et al. Omeprazole in the long-term treatment of gastro-oesophageal reflux disease. A double-blind randomized dose-finding study. Scand J Gastroenterol. 1995;30:839–46.

    Article  CAS  PubMed  Google Scholar 

  26. Vakil NB, Shaker R, Johnson DA, Kovacs T, Baerg RD, Hwang C, et al. The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety. Aliment Pharmacol Ther. 2001;15:927–35.

    Article  CAS  PubMed  Google Scholar 

  27. Plein K, Hotz J, Wurzer H, Fumagalli I, Lühmann R, Schneider A. Pantoprazole 20 mg is an effective maintenance therapy for patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2000;12:425–32.

    Article  CAS  PubMed  Google Scholar 

  28. Thjodleifsson B, Beker JA, Dekkers C, Bjaaland T, Finnegan V, Humphries TJ. Rabeprazole versus omeprazole in preventing relapse of erosive or ulcerative gastroesophageal reflux disease: a double-blind, multicenter, European trial. The European Rabeprazole Study Group. Dig Dis Sci. 2000;45:845–53.

    Article  CAS  PubMed  Google Scholar 

  29. Lauritsen K, Devière J, Bigard MA, Bayerdörffer E, Mózsik G, Murray F, et al. Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results. Aliment Pharmacol Ther. 2003;17:333–41.

    Article  CAS  PubMed  Google Scholar 

  30. Labenz J, Armstrong D, Lauritsen K, Katelaris P, Schmidt S, Schütze K, et al. Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study. Aliment Pharmacol Ther. 2005;22:803–11.

    Article  CAS  PubMed  Google Scholar 

  31. Devault KR, Johanson JF, Johnson DA, Liu S, Sostek MB. Maintenance of healed erosive esophagitis: a randomized six-month comparison of esomeprazole twenty milligrams with lansoprazole fifteen milligrams. Clin Gastroenterol Hepatol. 2006;4:852–9.

    Article  PubMed  Google Scholar 

  32. Goh KL, Benamouzig R, Sander P, Schwan T. EMANCIPATE. Efficacy of pantoprazole 20 mg daily compared with esomeprazole 20 mg daily in the maintenance of healed gastroesophageal reflux disease: a randomized, double-blind comparative trial—the EMANCIPATE study. Eur J Gastroenterol Hepatol. 2007;19:205–11.

    Article  CAS  PubMed  Google Scholar 

  33. Hatlebakk JG, Berstad A. Prognostic factors for relapse of reflux oesophagitis and symptoms during 12 months of therapy with lansoprazole. Aliment Pharmacol Ther. 1997;11:1093–9.

    Article  CAS  PubMed  Google Scholar 

  34. Jaspersen D, Diehl KL, Schoeppner H, Geyer P, Martens E. A comparison of omeprazole, lansoprazole and pantoprazole in the maintenance treatment of severe reflux oesophagitis. Aliment Pharmacol Ther. 1998;12:49–52.

    Article  CAS  PubMed  Google Scholar 

  35. Venables TL, Newland RD, Patel AC, Hole J, Copeman MB, Turbitt ML. Maintenance treatment for gastro-oesophageal reflux disease. A placebo-controlled evaluation of 10 milligrams omeprazole once daily in general practice. Scand J Gastroenterol. 1997;32:627–32.

    Article  CAS  PubMed  Google Scholar 

  36. Saitoh T, Fukushima Y, Otsuka H, Hirakawa J, Mori H, Asano T, et al. Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers. Aliment Pharmacol Ther. 2002;16:1811–7.

    Article  CAS  PubMed  Google Scholar 

  37. Shirai N, Furuta T, Moriyama Y, Okochi H, Kobayashi K, Takashima M, et al. Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH. Aliment Pharmacol Ther. 2001;15:1929–37.

    Article  CAS  PubMed  Google Scholar 

  38. Furuta T, Shirai N, Xiao F, Ohashi K, Ishizaki T. Effect of high-dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19. Clin Pharmacol Ther. 2001;70:484–92.

    Article  CAS  PubMed  Google Scholar 

  39. Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet. 2005;20:153–67.

    Article  CAS  PubMed  Google Scholar 

  40. Rosemary J, Adithan C. The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance. Curr Clin Pharmacol. 2007;2:93–109.

    Article  CAS  PubMed  Google Scholar 

  41. Furuta T, Shirai N, Kodaira M, Sugimoto M, Nogaki A, Kuriyama S, et al. Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori. Clin Pharmacol Ther. 2007;81:521–8.

    Article  CAS  PubMed  Google Scholar 

  42. Kawamura M, Ohara S, Koike T, Iijima K, Suzuki H, Kayaba S, et al. Cytochrome P450 2C19 polymorphism influences the preventive effect of lansoprazole on the recurrence of erosive reflux esophagitis. J Gastroenterol Hepatol. 2007;22:222–6.

    Article  CAS  PubMed  Google Scholar 

  43. Saitoh T, Otsuka H, Kawasaki T, Endo H, Iga D, Tomimatsu M, et al. Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during proton pump inhibitor maintenance therapy. Hepatogastroenterology. 2009;56:703–6.

    CAS  PubMed  Google Scholar 

  44. Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Ikuma M, et al. CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole. Eur J Clin Pharmacol. 2009;65:693–8.

    Article  CAS  PubMed  Google Scholar 

  45. Ohkusa T, Maekawa T, Arakawa T, Nakajima M, Fujimoto K, Hoshino E, et al. Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis. Aliment Pharmacol Ther. 2005;21:1331–9.

    Article  CAS  PubMed  Google Scholar 

  46. Pace F, Negrini C, Wiklund I, Rossi C, Savarino V. ITALIAN ONE INVESTIGATORS STUDY GROUP Quality of life in acute and maintenance treatment of non-erosive and mild erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2005;22:349–56.

    Article  CAS  PubMed  Google Scholar 

  47. Cibor D, Ciećko-Michalska I, Owczarek D, Szczepanek M. Optimal maintenance therapy in patients with non-erosive reflux disease reporting mild reflux symptoms—a pilot study. Adv Med Sci. 2006;51:336–9.

    CAS  PubMed  Google Scholar 

  48. Morgan DG, O’Mahony MF, O’Mahony WF, Roy J, Camacho F, Dinniwell J, et al. Maintenance treatment of gastroesophageal reflux disease: an evaluation of continuous and on-demand therapy with rabeprazole 20 mg. Can J Gastroenterol. 2007;21:820–6.

    CAS  PubMed  Google Scholar 

  49. Tepes B, Stabuc B, Kocijancic B, Ivanusa M. Maintenance therapy of gastroesophageal reflux disease patients with omeprazole. Hepatogastroenterology. 2009;56:67–74.

    CAS  PubMed  Google Scholar 

  50. Johnsson F, Moum B, Vilien M, Grove O, Simren M, Thoring M. On-demand treatment in patients with oesophagitis and reflux symptoms: comparison of lansoprazole and omeprazole. Scand J Gastroenterol. 2002;37:642–7.

    Article  CAS  PubMed  Google Scholar 

  51. Bytzer P, Blum A, De Herdt D, Dubois D. Trial Investigators. Six-month trial of on-demand rabeprazole 10 mg maintains symptom relief in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2004;20:181–8.

    Article  CAS  PubMed  Google Scholar 

  52. Tsai HH, Chapman R, Shepherd A, McKeith D, Anderson M, Vearer D, et al. Esomeprazole 20 mg on-demand is more acceptable to patients than continuous lansoprazole 15 mg in the long-term maintenance of endoscopy-negative gastro-oesophageal reflux patients: the COMMAND Study. Aliment Pharmacol Ther. 2004;20:657–65.

    Article  CAS  PubMed  Google Scholar 

  53. Norman Hansen A, Bergheim R, Fagertun H, Lund H, Moum B. A randomised prospective study comparing the effectiveness of esomeprazole treatment strategies in clinical practice for 6 months in the management of patients with symptoms of gastroesophageal reflux disease. Int J Clin Pract. 2005;59:665–71.

    Article  CAS  PubMed  Google Scholar 

  54. Pace F, Tonini M, Pallotta S, Molteni P, Porro GB. Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken ‘on-demand’. Aliment Pharmacol Ther. 2007;26:195–204.

    Article  CAS  PubMed  Google Scholar 

  55. Geboes K, Dekker W, Mulder CJ, Nusteling K. Dutch Study Group. Long-term lansoprazole treatment for gastro-oesophageal reflux disease: clinical efficacy and influence on gastric mucosa. Aliment Pharmacol Ther. 2001;15:1819–26.

    Article  CAS  PubMed  Google Scholar 

  56. Thjodleifsson B, Rindi G, Fiocca R, Humphries TJ, Morocutti A, Miller N, et al. A randomized, double-blind trial of the efficacy and safety of 10 or 20 mg rabeprazole compared with 20 mg omeprazole in the maintenance of gastro-oesophageal reflux disease over 5 years. Aliment Pharmacol Ther. 2003;17:343–51.

    Article  CAS  PubMed  Google Scholar 

  57. Caos A, Breiter J, Perdomo C, Barth J. Long-term prevention of erosive or ulcerative gastro-oesophageal reflux disease relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in the United States. Aliment Pharmacol Ther. 2005;22:193–202.

    Article  CAS  PubMed  Google Scholar 

  58. Miyamoto M, Haruma K, Kuwabara M, Nagano M, Okamoto T, Tanaka M. Long-term gastroesophageal reflux disease therapy improves reflux symptoms in elderly patients: five-year prospective study in community medicine. J Gastroenterol Hepatol. 2007;22:639–44.

    Article  PubMed  Google Scholar 

  59. Miki K, Urita Y. Using serum pepsinogens wisely in a clinical practice. J Dig Dis. 2007;8(1):8–14.

    Article  CAS  PubMed  Google Scholar 

  60. Miki K, Ichinose M, Shimizu A, Huang SC, Oka H, Furihata C, et al. Serum pepsinogens as a screening test of extensive chronic gastritis. Gastroenterol Jpn. 1987;22:133–41.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Akihito Nagahara, Mariko Hojo, Daisuke Asaoka & Sumio Watanabe

Authors
  1. Akihito Nagahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariko Hojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Asaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sumio Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akihito Nagahara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagahara, A., Hojo, M., Asaoka, D. et al. Maintenance therapy of gastroesophageal reflux disease. Clin J Gastroenterol 3, 61–68 (2010). https://doi.org/10.1007/s12328-010-0139-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-010-0139-z

Keywords

Search

Navigation