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  • Review Article
  • Published:

Management of refractory typical GERD symptoms

Nature Reviews Gastroenterology & Hepatology volume 13, pages 281–294 (2016)Cite this article

Subjects

Key Points

  • Patients with refractory GERD (rGERD) are those individuals whose symptoms do not respond to a stable double dose of a PPI during a treatment period of at least 12 weeks

  • Weakly acidic reflux episodes have been implicated in symptom generation in patients with rGERD

  • Several reflux inhibitors have been studied for rGERD treatment, but development was discontinued because of limited clinical efficacy and poor tolerance profiles

  • Antidepressant drugs are emerging as potentially efficacious neuromodulatory therapies for patients with rGERD

  • Data suggests that antireflux surgery has lower efficacy in rGERD than in GERD

  • The experience with novel endoscopic or surgical techniques is limited and their application requires large-scale studies

Abstract

The management of patients with refractory GERD (rGERD) is a major clinical challenge for gastroenterologists. In up to 30% of patients with typical GERD symptoms (heartburn and/or regurgitation), acid-suppressive therapy does not provide clinical benefit. In this Review, we discuss the current management algorithm for GERD and the features and management of patients who do not respond to treatment (such as those individuals with an incorrect diagnosis of GERD, inadequate PPI intake, persisting acid reflux and persisting weakly acidic reflux). Symptom response to existing surgical techniques, novel antireflux procedures, and the value of add-on medical therapies (including prokinetics and reflux inhibitors) for rGERD symptoms are discussed. Pharmaceutical agents targeting oesophageal sensitivity, a condition that can contribute to symptom generation in rGERD, are also discussed. Finally, on the basis of available published data and our expert opinion, we present an outline of a current, usable algorithm for management of patients with rGERD that considers the timing and diagnostic use of pH–impedance monitoring on or off PPI, additional diagnostic tests, the clinical use of baclofen and the use of add-on neuromodulators (tricyclic agents and selective serotonin reuptake inhibitors).

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Figure 1: Current treatment algorithm for patients with typical GERD symptoms.
Figure 2: Responder rates in studies investigating the effect of prokinetic drugs as add-ons to acid-suppressive therapy for rGERD.
Figure 3: Responder rates in studies evaluating reflux inhibitors, either as monotherapy or as an add-on to acid suppressive therapy, for rGERD.
Figure 4: Current management algorithm for typical rGERD symptoms in the opinion of the authors, accounting for access to MII-pH monitoring.

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Authors and Affiliations

  1. Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, Leuven, B-3000, Belgium

    Emidio Scarpellini, Ans Pauwels, Tim Vanuytsel & Jan Tack

  2. Division Gastroenterology, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00100, Italy

    Emidio Scarpellini

  3. Division of Gastroenterology, Changi General Hospital, 2 Simei Street 3, 529889, Singapore

    Daphne Ang & Adriano De Santis

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Contributions

All authors contributed equally to editing and reviewing of the article. J.T., E.S. and D.A. researched data for the manuscript. J.T. and E.S. wrote the article. J.T., E.S., A.P. and T.V. substantially contributed to the discussion of content.

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Correspondence to Jan Tack.

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Competing interests

J.T. has given scientific advice to Abide Therapeutics, Alfa Wassermann, Almirall, AstraZeneca, Danone, GlaxoSmithKline, Ironwood, Janssen, Menarini, Novartis, Rhythm, Shire, Sucampo Pharmaceuticals, Takeda, Theravance Biopharma, Tsumura & Co., Yuhan Co., and Zeria Pharmaceutical Co. He has received grant support from Abide Therapeutics, Novartis, Shire and Zeria Pharmaceutical Co. and has served on the speaker bureau for Abbott, Almirall, AstraZeneca, Janssen, Menarini, Novartis, Shire, Takeda and Zeria Pharmaceutical Co. The other authors declare no competing interests.

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Scarpellini, E., Ang, D., Pauwels, A. et al. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol 13, 281–294 (2016). https://doi.org/10.1038/nrgastro.2016.50

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