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

David Armstrong; A Pali Hungin; Peter J Kahrilas; Daniel Sifrim; Paul Moayyedi; Michael F Vaezi; Sameer Al-Awadhi; Sama Anvari; Reginald Bell; Brendan Delaney; Fabian Emura; C Prakash Gyawali; Peter Katelaris; Adriana Lazarescu; Yeong Yeh Lee; Alessandro Repici; Sabine Roman; Ceciel T Rooker; Edoardo Vincenzo Savarino; Paul Sinclair; Kentaro Sugano; Rena Yadlapati; Yuhong Yuan; Frank Zerbib; Prateek Sharma; International Working Group for the Classification of Oesophagitis (IWGCO)

doi:10.1111/apt.18420

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

Aliment Pharmacol Ther. 2024 Dec 30. doi: 10.1111/apt.18420. Online ahead of print.

Authors

David Armstrong¹, A Pali Hungin², Peter J Kahrilas³, Daniel Sifrim⁴, Paul Moayyedi¹, Michael F Vaezi⁵, Sameer Al-Awadhi⁶, Sama Anvari¹, Reginald Bell⁷, Brendan Delaney⁸, Fabian Emura^{9

10}, C Prakash Gyawali¹¹, Peter Katelaris¹², Adriana Lazarescu¹³, Yeong Yeh Lee¹⁴, Alessandro Repici¹⁵, Sabine Roman¹⁶, Ceciel T Rooker¹⁷, Edoardo Vincenzo Savarino¹⁸, Paul Sinclair¹⁹, Kentaro Sugano²⁰, Rena Yadlapati²¹, Yuhong Yuan¹, Frank Zerbib²², Prateek Sharma²³; 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 Gastroenterology Division, Universidad de La Sabana, Chia, Cundinamarca, Colombia.
¹¹ Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA.
¹² Gastroenterology Department, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia.
¹³ Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
¹⁴ GI Function & Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia.
¹⁵ Department of Gastroenterology, IRCCS Istituto Clinico Humanitas, Rozzano (Milano), Italy.
¹⁶ Division of Digestive Physiology, Centre Hospitalier Universitaire de Lyon, Lyon, France.
¹⁷ International Foundation for Functional Gastrointestinal Disorders (IFFGD), Mount Pleasant, South Carolina, USA.
¹⁸ Gastroenterology Unit, Azienda Ospedale Università di Padova, Padova, Italy.
¹⁹ INSINC Consulting Inc., Guelph, Ontario, Canada.
²⁰ Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi-ken, Japan.
²¹ Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
²² CHU de Bordeaux, Centre Médico-Chirurgical Magellan, Hôpital Haut-Levêque, Department of Gastroenterology, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France.
²³ Division of Gastroenterology and Hepatology, University of Kansas School of Medicine, and Kansas City VA Medical Center, Kansas City, Missouri, USA.

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.

Keywords: GRADE; endoscopy; gastro‐oesophageal reflux disease (GERD); manometry; pH‐impedance; refractory.

Grants and funding

Independent educational grants to the IWGCO from Cinclus Pharma, Ironwood Pharmaceuticals, and Phathom Pharmaceuticals