Management of Patients With Refractory Reflux-Like Symptoms Despite Proton Pump Inhibitor Therapy: Evidence-Based Consensus Statements

Armstrong D 1 , Hungin AP 2 , Kahrilas PJ 3 , Sifrim D 4 , Moayyedi P 1 , Vaezi MF 5 Show all authors , Al-Awadhi S 6 , Anvari S 1 , Bell R 7 , Delaney B 8 , Emura F 9 , Gyawali CP 10 , Katelaris P 11 , Lazarescu A 12 , Lee YY 13 , Repici A 14 , Roman S 15 , Rooker CT 16 , Savarino EV 17 , Sinclair P 18 , Sugano K 19 , Yadlapati R 20 , Yuan Y 1 , Zerbib F 21 , Sharma P 22 , International Working Group for the Classification of Oesophagitis (IWGCO)

Affiliations 

  • 1 Division of Gastroenterology & Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  • 2 Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
  • 3 Division of Gastroenterology, Northwestern University, Chicago, Illinois, USA
  • 4 Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  • 5 Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  • 6 Department of Gastroenterology, Rashid Hospital, Dubai Academic Health Corporation, Dubai, UAE
  • 7 Institute of Esophageal and Reflux Surgery, Englewood, Colorado, USA
  • 8 Department of Surgery and Cancer, Imperial College London, Saint Mary's Campus, London, UK
  • 9 Digestive Health and Liver Diseases, Miller School of Medicine, University of Miami, Miami, Florida, USA
  • 10 Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
  • 11 Gastroenterology Department, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia
  • 12 Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  • 13 GI Function & Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia
  • 14 Department of Gastroenterology, IRCCS Istituto Clinico Humanitas, Rozzano (Milano), Italy
  • 15 Division of Digestive Physiology, Centre Hospitalier Universitaire de Lyon, Lyon, France
  • 16 International Foundation for Functional Gastrointestinal Disorders (IFFGD), Mount Pleasant, South Carolina, USA
  • 17 Gastroenterology Unit, Azienda Ospedale Università di Padova, Padova, Italy
  • 18 INSINC Consulting Inc., Guelph, Ontario, Canada
  • 19 Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi-ken, Japan
  • 20 Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
  • 21 CHU de Bordeaux, Centre Médico-Chirurgical Magellan, Hôpital Haut-Levêque, Department of Gastroenterology, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
  • 22 Division of Gastroenterology and Hepatology, University of Kansas School of Medicine, and Kansas City VA Medical Center, Kansas City, Missouri, USA
Aliment Pharmacol Ther, 2025 Feb;61(4):636-650.
PMID: 39740235 DOI: 10.1111/apt.18420

Abstract

BACKGROUND: Many patients diagnosed with gastro-oesophageal reflux disease (GERD) have persistent symptoms despite proton pump inhibitor (PPI) therapy.

AIMS: The aim of this consensus is to provide evidence-based statements to guide clinicians caring for patients with refractory reflux-like symptoms (rRLS) or refractory GERD.

METHODS: This consensus was developed by the International Working Group for the Classification of Oesophagitis. The steering committee developed specific PICO questions pertaining to the management of PPI rRLS. Methodologists conducted systematic reviews of the literature. The quality of evidence and strength of recommendations were rated using the GRADE approach.

RESULTS: Consensus was reached on 13 of 17 statements on diagnosis and management. For rRLS, suggested diagnostic strategies included endoscopy, ambulatory reflux testing and oesophageal manometry. The group did not reach consensus on the role of oesophageal biopsies or the use of reflux-symptom association in patients undergoing reflux testing. The group suggested against increasing the PPI dose in patients who had received 8 weeks of a twice-daily PPI. Adjunctive alginate or antacid therapy was suggested. There was no consensus on the role of adjunctive prokinetics. There was little role for adjunctive transient lower oesophageal sphincter relaxation (TLESR) inhibitors or bile acid sequestrants. Endoscopic or surgical anti-reflux procedures should not be performed in patients with rRLS in the absence of objectively confirmed GERD.

CONCLUSIONS: The management of rRLS should be personalised, based on shared decision-making regarding the role of diagnostic testing to confirm or rule out GERD as a basis for treatment optimisation. Anti-reflux procedures should not be performed without objective confirmation of GERD.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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