Advertisement

Acid Suppression for Reflux Disease: “Off-the-Peg” or a Tailored Approach?

Published:December 02, 2011DOI:https://doi.org/10.1016/j.cgh.2011.11.018
      The apparent superiority of the proton pump inhibitors (PPIs) over the H2-receptor antagonists (H2RAs) in the management of gastroesophageal reflux disease (GERD) has convinced most physicians and payers that these drugs cannot be bettered. However, there is convincing evidence that more than 50% of patients taking a PPI are dissatisfied with their treatment,
      • Fass R.
      • Sifrim D.
      Management of heartburn not responding to proton pump inhibitors.
      and more than 20% take twice daily PPIs or supplement their treatment with over-the-counter remedies.
      • Chey W.D.
      • Mody R.R.
      • Izat E.
      Patient and physician satisfaction with proton pump inhibitors (PPIs): are there opportunities for improvement?.
      For these patients who have an unsatisfactory response to once daily PPI, increasing to twice a day (before breakfast and before dinner) is a common practice, as suggested in the 2008 American Gastroenterological Association statement.
      • Kahrilas P.J.
      • Shaheen N.J.
      • Vaezi M.F.
      • et al.
      American Gastroenterological Association: American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease.
      Among patients on PPI twice a day, 39% increased the dose because of poor symptom control at night,
      • Chey W.D.
      • Mody R.R.
      • Izat E.
      Patient and physician satisfaction with proton pump inhibitors (PPIs): are there opportunities for improvement?.
      and in a recent U.S. survey of GERD patients taking PPIs, >80% reported severe symptoms at night.
      • Chey W.D.
      • Mody R.
      • Chen L.
      • et al.
      Nighttime symptoms and sleep impairment among patients with gastro-esophageal reflux disease (GERD) receiving prescription (Rx) proton pump inhibitors (PPIs).
      In total, 22% of responders were on PPI twice a day, and 42% supplemented prescribed PPIs with over-the-counter PPIs, H2-RAs, or antacids. Not surprisingly, the practice of prescribing PPIs in high dose or twice daily is increasing,
      • Targownik L.E.
      • Metge C.
      • Roos L.
      • et al.
      The prevalence of and the clinical and demographic characteristics associated with high-intensity proton pump inhibitor use.
      despite high dose or twice a day PPIs not being approved for GERD in any jurisdiction. Indeed, it is remarkable that 20 years after their introduction, the PPIs are still marketed and prescribed as “one drug, once a day for all acid related disorders.” This “off-the-peg” approach flies in the face of our understanding of the pathophysiology of the underlying diseases and the fickle pharmacology of the PPIs. Thus, a renewed appreciation of these issues should prompt us to tailor drug therapy as we do in many other diseases.
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Fass R.
        • Sifrim D.
        Management of heartburn not responding to proton pump inhibitors.
        Gut. 2009; 58: 295-309
        • Chey W.D.
        • Mody R.R.
        • Izat E.
        Patient and physician satisfaction with proton pump inhibitors (PPIs): are there opportunities for improvement?.
        Dig Dis Sci. 2010; 55: 3415-3422
        • Kahrilas P.J.
        • Shaheen N.J.
        • Vaezi M.F.
        • et al.
        American Gastroenterological Association: American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease.
        Gastroenterology. 2008; 135: 1383-1391
        • Chey W.D.
        • Mody R.
        • Chen L.
        • et al.
        Nighttime symptoms and sleep impairment among patients with gastro-esophageal reflux disease (GERD) receiving prescription (Rx) proton pump inhibitors (PPIs).
        Gastroenterology. 2008; 134: A323-A324
        • Targownik L.E.
        • Metge C.
        • Roos L.
        • et al.
        The prevalence of and the clinical and demographic characteristics associated with high-intensity proton pump inhibitor use.
        Am J Gastroenterol. 2007; 102: 942-950
        • Fass R.
        • Inadomi J.
        • Han C.
        • et al.
        Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release.
        Clin Gastroenterol Hepatol. 2012; 10: 247-253
        • Coté G.A.
        • Ferreira M.R.
        • Rozenberg-Ben-Dror K.
        • et al.
        Programme of stepping down from twice daily proton pump inhibitor therapy for symptomatic gastro-oesophageal reflux disease associated with a formulary change at a VA medical center.
        Aliment Pharmacol Ther. 2007; 25: 709-714
        • Howden C.W.
        • Kahrilas P.J.
        Just how “difficult” is it to withdraw PPI treatment?.
        Am J Gastroenterol. 2010; 105: 1538-1540
        • Metz D.C.
        • Vakily M.
        • Dixit T.
        • et al.
        Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy.
        Aliment Pharmacol Ther. 2009; 29: 928-937
        • Vakily M.
        • Zhang W.
        • Wu J.
        • et al.
        Pharmacokinetics and pharmaco-dynamics of a known active PPI with a novel Dual Delayed Release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials.
        Curr Med Res Opin. 2009; 25: 627-638
        • Orr W.C.
        Reflux events and sleep: are we vulnerable?.
        Curr Gastroenterol Rep. 2006; 8: 202-207
        • Peghini P.L.
        • Katz P.O.
        • Bracy N.A.
        • et al.
        Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors.
        Am J Gastroenterol. 1998; 93: 763-767
        • Gerson L.B.
        • Triadafilopoulos G.
        • Sahbaie P.
        • et al.
        Time esophageal pH <4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors.
        BMC Gastroenterol. 2008; 8: 15
        • Wang C.C.
        • Yuan Y.
        • Chen Y.
        • et al.
        Night-time pH holding time: what is hidden by the % of time pH <4?.
        Am J Gastroenterol. 2008; 103 (no 130): S51
        • Galmiche J.P.
        • Zerbib F.
        • Bruley des Varannes S.
        Review article: respiratory manifestations of gastro-oesophageal reflux disease.
        Aliment Pharmacol Ther. 2008; 27: 449-464
        • Shaker R.
        • Castell D.O.
        • Schoenfeld P.S.
        • et al.
        Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association.
        Am J Gastroenterol. 2003; 98: 1487-1493
        • Tytgat G.N.
        Are there unmet needs in acid suppression?.
        Best Pract Res Clin Gastroenterol. 2004; 18: 67-72
        • Wang C.
        • Hunt R.H.
        Precise role of acid in nonerosive reflux disease.
        Digestion. 2008; 78: 31-41
        • Dean B.B.
        • Gano Jr, A.D.
        • Knight K.
        • et al.
        Effectiveness of proton pump inhibitors in non-erosive reflux disease.
        Clin Gastroenterol Hepatol. 2004; 2: 656-664
        • Fass R.
        Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics.
        J Clin Gastroenterol. 2007; 41: 131-137
        • El-Serag H.B.
        Epidemiology of nonerosive reflux disease.
        Digestion. 2008; 78: 6-10
        • Weijenborg P.W.
        • Cremonini F.
        • Smout A.J.P.M.
        • et al.
        PPI-therapy is as effective in well-defined NERD patients as in patients with reflux esophagitis: a meta-analysis.
        Gut. 2011; 60: A37
        • Bell N.J.
        • Burget D.
        • Howden C.W.
        • et al.
        Appropriate acid suppression for the management of gastro-oesophageal reflux disease.
        Digestion. 1992; 51: 59-67
        • Howden C.W.
        • Burget D.W.
        • Hunt R.H.
        Appropriate acid suppression for optimal healing of duodenal ulcer and gastro-oesophageal reflux disease.
        Scand J Gastroenterol Suppl. 1994; 201: 79-82
        • Hunt R.H.
        Importance of pH control in the management of GERD.
        Arch Intern Med. 1999; 159: 649-657
        • Yuan Y.
        • Hunt R.H.
        Intragastric pH holding time pH <3 at steady state in healthy volunteers (HV) after once daily PPIs: a predictor for low erosive esophagitis (EE) healing rates?.
        Gastroenterology. 2009; 136: M1900
        • Smith J.L.
        • Opekun A.R.
        • Larkai E.
        • et al.
        Sensitivity of the esophageal mucosa to pH in gastroesophageal reflux disease.
        Gastroenterology. 1989; 96: 683-689
        • Johnson L.F.
        • Demeester T.R.
        Twenty-four-hour pH monitoring of the distal esophagus: a quantitative measure of gastroesophageal reflux.
        Am J Gastroenterol. 1974; 62: 325-332
        • Ribolsi M.
        • Emerenziani S.
        • Caviglia R.
        • et al.
        Short duration of acid exposure sensitizes the esophagus to perception of weakly acidic and mixed reflux in nonerosive reflux disease (NERD) patients.
        Gastroenterology. 2008; 134: A593
        • Karamanolis G.
        • Vanuytsel T.
        • Sifrim D.
        • et al.
        Yield of 24-h esophageal pH and bilitec monitoring in patients with persisting symptoms on PPI therapy.
        Dig Dis Sci. 2008; 53: 2387-2393
        • Yuan Y.
        • Hunt R.H.
        Intragastric acid suppressing effect of proton pump inhibitors twice daily at steady state in healthy volunteers: evidence of an unmet need?.
        Am J Gastroenterol. 2008; 103 (no 128): S50
        • Mackalski B.A.
        • Ilnyckyj A.
        Esophageal pH testing in patients refractory to proton pump inhibitor therapy.
        Can J Gastroenterol. 2008; 22: 249-252
        • Hunt R.H.
        Review article: the unmet needs in delayed-release proton-pump inhibitor therapy in 2005.
        Aliment Pharmacol Ther. 2005; 22: 10-19
        • Katz P.O.
        • Scheiman J.M.
        • Barkun A.N.
        Review article: acid-related disease—what are the unmet clinical needs?.
        Aliment Pharmacol Ther. 2006; 23: 9-22
        • Scarpignato C.
        • Hunt R.H.
        Proton pump inhibitors: the beginning of the end or the end of the beginning?.
        Curr Opin Pharmacol. 2008; 8: 677-684
        • Sachs G.
        • Shin J.M.
        • Hunt R.
        Novel approaches to inhibition of gastric acid secretion.
        Curr Gastroenterol Rep. 2010; 12: 437-447
        • Vakil N.
        New pharmacological agents for the treatment of gastroesophageal reflux disease.
        Rev Gastroenterol Disord. 2008; 8: 117-122
        • Hunt R.H.
        • Armstrong D.
        • Yaghoobi M.
        • et al.
        Predictable prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904-Z.
        Aliment Pharmacol Ther. 2008; 28: 187-199
        • Hunt R.H.
        • Armstrong D.
        • James C.
        • et al.
        Effect on intragastric pH of a PPI with a prolonged plasma half-life: comparison between tenatoprazole and esomeprazole on the duration of acid suppression in healthy male volunteers.
        Am J Gastroenterol. 2005; 100: 1949-1956

      Linked Article