Management of Patients With Refractory Reflux-LikeSymptoms Despite Proton Pump Inhibitor Therapy:Evidence-Based Consensus Statements
David Armstrong et al. on behalf of the International Working Group for the Classification of Oesophagitis (IWGCO)
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.
1 Introduction
Gastro-oesophageal reflux disease (GERD) is one of the most common diagnoses in clinical practice. Globally, GERD is estimated to affect 4%–14% of the population [1]. Whilst proton pump inhibitors (PPIs) are the mainstay of treatment for GERD, an estimated 45%–55% of patients in observational studies have persistent symptoms despite therapy [2, 3]. Heartburn and regurgitation have been defined as the characteristic symptoms of the typical reflux syndrome [4], and the consensus group was convened to address the management of refractory reflux-like symptoms (rRLS); that is, characteristic symptoms that persist despite treatment. Patients with rRLS despite therapy may or may not have an objective diagnosis of GERD, and it has been suggested that the specific term refractory GERD (rGERD) is used only for patients with persisting symptoms in whom GERD features have been demonstrated by endoscopy or oesophageal reflux testing [5]. However, it should be recognised that when the term rGERD is applied to patients in the published literature, there is marked variability in the definitions of rGERD. In practice, endoscopic features of GERD may not be present in patients who have refractory symptoms after a course of PPI therapy; conversely, endoscopic features of GERD may occur in the absence of typical symptoms. Furthermore, oesophageal reflux testing is not widely available and has not been an inclusion criterion for many rGERD studies. For the purposes of this consensus process, rGERD and rRLS will refer to patients whose condition is refractory to PPI therapy, regardless of whether or not they have received other treatments, including lifestyle changes, antacids, H2 receptor antagonists (H2RAs), potassium-competitive acid blockers (PCABs), motility agents or surgery.
In patients without objective evidence of GERD, it is important to exclude other potential causes when symptoms have not resolved with PPI therapy. Even in patients who have reflux-related abnormalities at endoscopy or oesophageal reflux testing, the symptoms may not be reflux-related [5]. Other diagnoses such as eosinophilic oesophagitis (EoE) and disorders of gut–brain interaction (DGBI), including functional heartburn, functional dyspepsia, rumination syndrome, supragastric belching and motility disorders, should be considered [5–8], as should cardiac or pulmonary conditions.
Patients should not be considered to have rRLS unless they have undergone an adequate trial of PPI therapy, defined as 8 weeks of treatment with a twice-daily PPI [6, 9]. In addition, it is important to ensure that the PPI therapy has been optimised with respect to both dosing and time of administration. Currently available PPIs vary markedly in potency as characterised by the duration of acid suppression (hours per day with gastric pH above 4) [10]. Thus, although meta-analyses suggest that overall GERD symptom relief and healing rates are similar for the available PPIs [11–13], pharmacodynamic studies show marked differences in acid suppression potencies (Table 1), and it may therefore be reasonable to consider switching PPIs if the patient has rRLS [10, 14].
