Clinical Role of Ambulatory Reflux Monitoring in PPI Non-responders

Recommendation Statements

Rena Yadlapati; Andrew J. Gawron; C. Prakash Gyawali; Joan Chen; John Clarke; Ronnie Fass; Anand Jain; Kristle Lynch; Abraham Khan; Philip O. Katz; David A. Katzka; Joel Richter; Felice Schnoll-Sussman; Stuart J. Spechler; Michael F. Vaezi; Marcelo Vela; John E. Pandolfino

Disclosures

Aliment Pharmacol Ther. 2022;56(8):1274-1283.

Abstract and Introduction

Abstract

Background: Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated.

Aims: To utilise published literature and expert opinion to develop recommendation statements addressing use of ambulatory reflux monitoring in clinical practice

Methods: The RAND Appropriateness Method (RAM) was utilised among 17 experts with discussion, revision and two rounds of ranking of recommendation statements. Ambulatory reflux monitoring protocol, methodology and thresholds ranked as appropriate by ≥80% of panellists met the criteria for appropriateness.

Results: Prolonged (96-h recommended) wireless pH monitoring off proton pump inhibitor (PPI) was identified as the appropriate diagnostic tool to assess the need for acid suppression in patients with unproven gastro-oesophageal reflux disease (GERD) and persisting typical reflux symptoms despite once-daily PPI. Acid exposure time (AET) <4.0% on all days of monitoring with negative reflux-symptom association excludes GERD and does not support ongoing PPI treatment. Conversely, AET >6.0% across ≥2 days is conclusive evidence for GERD and supports treatment for GERD, while AET >10% across ≥2 days identifies severe acid burden that supports escalation of anti-reflux treatment. In previously proven GERD, impedance-pH monitoring on PPI is helpful in defining refractory GERD and mechanisms of continued symptoms; the presence of <40 reflux events, AET <2.0% and a negative reflux-symptom association does not support escalation of anti-reflux treatment. In contrast, AET > 4.0% and positive reflux-symptom association support escalation of anti-reflux treatment, including use of invasive therapeutics.

Conclusions: Statements meeting appropriateness for average clinical care have been identified when utilising reflux monitoring in patients with typical reflux symptoms and PPI non-response.

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Abstract and Introduction
Background
Methods
Results
Discussion
References

Table 1. Final recommendation statements
Final recommendation statements	Median (range)	% agreement
Role/protocol of wireless pH monitoring
Prolonged wireless pH monitoring off PPI is the preferred diagnostic tool to assess need for acid suppression in patients with unproven GERD and typical reflux symptoms (heartburn/regurgitation) not adequately responding to single-dose PPI therapy	8 (7, 9)	100% Appropriate
The preferred duration for wireless pH monitoring off acid suppression is 96 h	8 (4, 9)	88% Appropriate
Prolonged wireless pH monitoring off PPI—thresholds
In patients with symptoms of heartburn, regurgitation and/or non-cardiac chest pain not responsive to single-dose PPI, an acid exposure time less than 4.0% on all days of monitoring and an overall negative reflux-symptom association on prolonged wireless pH monitoring off PPI therapy does not support treatment of GERD with a PPI	9 (2, 9)	94% Appropriate
In patients with symptoms of heartburn, regurgitation and/or non-cardiac chest pain not responsive to single-dose PPI, an acid exposure time greater than 6.0% across 2 or more days is diagnostic of and supports treatment for GERD	9 (7, 9)	100% Appropriate
In patients with symptoms of heartburn, regurgitation and/or non-cardiac chest pain and proven GERD, an acid exposure time greater than 10% across 2 or more days on prolonged wireless pH monitoring off acid suppression is consistent with severe acid burden and supports escalation of anti-reflux treatment	9 (6, 9)	94% Appropriate
pH impedance on PPI—thresholds
In patients with proven GERD, 24-h pH impedance on PPI therapy is helpful in defining refractory GERD and mechanisms of continued symptoms	8 (4, 9)	88% Appropriate
In patients with proven GERD with ongoing symptoms despite optimised PPI therapy undergoing pH impedance monitoring on double dose PPI therapy, the presence of fewer than 40 reflux events, an acid exposure time less than 2.0% and a negative reflux-symptom association does not support escalation of anti-reflux treatment	9 (7, 9)	100% Appropriate
In patients with proven GERD with ongoing symptoms despite optimised PPI therapy undergoing pH impedance monitoring on double dose PPI therapy, the presence of an acid exposure time greater than 4.0% and positive reflux-symptom association supports escalation of anti-reflux treatment	8 (5, 9)	94% Appropriate

Authors and Disclosures

Rena Yadlapati¹, Andrew J. Gawron^2,3, C. Prakash Gyawali⁴, Joan Chen⁵, John Clarke⁶, Ronnie Fass⁷, Anand Jain⁸, Kristle Lynch⁹, Abraham Khan¹⁰, Philip O. Katz¹¹, David A. Katzka^12,13, Joel Richter¹⁴, Felice Schnoll-Sussman¹¹, Stuart J. Spechler¹⁵, Michael F. Vaezi¹⁶, Marcelo Vela¹⁷ and John E. Pandolfino¹⁸

¹Division of Gastroenterology & Hepatology, University of California San Diego, La Jolla, California, USA
²University of Utah, Salt Lake City, Utah, USA
³Salt Lake City VA Medical Center, Salt Lake City, Utah, USA
⁴Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
⁵Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
⁶Division of Gastroenterology, Stanford University, Palo Alto, California, USA
⁷Division of Gastroenterology, MetroHealth System, Cleveland, Ohio, USA
⁸Division of Gastroenterology, Emory University, Atlanta, Georgia, USA
⁹Division of Gastroenterology & Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
¹⁰Center for Esophageal Health, Division of Gastroenterology & Hepatology, NYU Langone Health, New York City, New York, USA
¹¹Division of Gastroenterology, Weill-Cornell Medical Center, New York City, New York, USA
¹²Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
¹³Division of Gastroenterology, Columbia Presbyterian Medical Center, New York City, New York, USA
¹⁴Division of Gastroenterology, University of South Florida, Tampa, Florida, USA
¹⁵Division of Gastroenterology, Baylor Scott & White Health, Dallas, Texas, USA
¹⁶Division of Gastroenterology, Vanderbilt Medical Center, Nashville, Tennessee, USA
¹⁷Division of Gastroenterology, Mayo Clinic, Phoenix, Arizona, USA
¹⁸Division of Gastroenterology, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA

Correspondence
Rena Yadlapati, 9500 Gilman Drive MC0956, La Jolla, CA 92093, USA. Email: ryadlapati@health.ucsd.edu

Author Contributions
Rena Yadlapati: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (supporting); investigation (equal); methodology (equal); project administration (equal); supervision (equal); writing – original draft (equal); writing – review and editing (equal). Andrew Gawron: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); methodology (equal); writing – original draft (supporting); writing – review and editing (supporting). C. Prakash Gyawali: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Joan Weichun Chen: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). John Clarke: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Ronnie Fass: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Anand Jain: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Kristle Lynch: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Abraham Khan: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). David A. Katzka: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Joel E. Richter: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Felice Schnoll-Sussman: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Stuart Jon Spechler: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Michael Vaezi: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). Marcelo F Vela: Investigation (supporting); writing – original draft (supporting); writing – review and editing (supporting). John E Pandolfino: Conceptualization (equal); formal analysis (equal); funding acquisition (lead); investigation (equal); methodology (equal); project administration (equal); supervision (equal); writing – original draft (equal); writing – review and editing (equal).

Declaration of personal interests
RY: Consultant: Medtronic, Phathom Pharmaceuticals: RJS Mediagnostix, Stat DataLink. CPG: Consultant: Medtronic, Diversatek, Ironwood, Iso-Thrive, Quintiles, Takeda, Johnson&Johnson. JC: Consulting agreement—Phathom Pharmaceuticals. John Clarke: Consultant: Alnylam, Isothrive, Medtronic, Phathom Pharmaceuticals, Pfizer, Regeneron, Sanofi. RF: Advisor—Takeda, Medtronic, Phathom Pharmaceuticals, Neurogastrx, GERDCar, Celexio, Evoke Pharma Speaker—Astrazeneca, Takeda, GI Supply, Eisai, Johnson & Johnson. KL: Consultant Medtronic, Takeda, LUCID. AK: Consultant: Medtronic. POK: Consultant: Phathom Pharma, Takeda. DAK: Consulting for Takeda, Celgene and Regeneron. JR: Consultant for Medtronic. FSS: Consultant: Ethicon, Interpace, Medtronic. SJS: Consultant for Phathom Pharmaceuticals, Takeda Pharmaceuticals, Ironwood Pharmaceuticals, Interpace Diagnostics, Castle Biosciences, and ISOThrive. MFV: Ironwood, Phathom, ISOthrive, Sanofi, Bayer, Medtronic, Diversatek. Legal-consultation in litigations relating to acid suppressive therapy; Patent on Mucosal Integrity testing. MV: Medtronic—Consultant, Diversatek—Research Support. JEP: Consultant: Medtronic, Diversatek, Ethicon/Torax, Endogastric solutions, Takeda, Astra Zeneca, Phathom, Neurogastrx, Ironwood. AJG, AJ: None.