Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What is erosive GERD and who does the condition affect?
Gastroesophageal Reflux Disease (GERD) is a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications.
According to the findings at upper digestive endoscopy GERD may be erosive (when erosions are observed) or non-erosive (when the mucosa is normal or the findings are uncharacteristic such as oedema, erythema, etc.).
In general the non-erosive GERD is more frequent than the erosive, but the clinical picture of both presentations are the same (typical symptoms: heartburn and/or regurgitation; atypical symptoms: chronic laryngeal symptoms, cough, asthma, hoarseness, etc). The intensity of the manifestations not necessarily correlates with the severity of the oesophageal lesions.
Studies on the prevalence of GERD are relatively limited but it is accepted that in the ocidental world in general it is high, affecting 12 to 20% of the population.
What impact do the symptoms of GERD have on the quality of patients’ lives?
Health-related quality of life (HQoL) assessment is based upon the application of questionnaires that allows for an objective evaluation of clinical evolution, impact of the illness and response to the treatment.
The GERD patients show important impairment of HRQoL. As such, in general these patients present poor HRQoL when compared to the general population which improves or normalizes after the adequate treatment.
What treatments are currently used to treat erosive GERD?
The primary treatment objectives are the alleviation of symptoms, the healing of mucosal lesions and the prevention of recurrence and complications.
The therapeutic approach can be divided into behavioural and pharmacological measures that should be implemented simultaneously. As the compliance to the treatment is crucial, the partnership with the assistant physician is fundamental to the adoption of all the proposed measures.
The behavioural measures or lifestyle modifications (elevation of headboard of the bed, diet, avoidance of lying down for 2-3 h after meals, etc.) for treating GERD are still somewhat debatable, but obesity should be considered as an aggravating factor of reflux. On the other hand, the recommendation of the lifestyle modifications usually helps the treatment and should be considered as part of the therapy.
The pharmacological treatment of GERD consists in the use of proton pump inhibitors (PPIs) which is well established. This class of drugs (omeprazole, pantoprazole, rabeprazole, lansoprazole, esomeprazole, pantoprazole-Mg) is indicated as the first line of treatment to relieve the symptoms and/or healing the oesophageal lesions. An 8-week course of PPIs is the therapy of choice for symptom relief and healing of erosive esophagitis. As far as the complete remission (confirmed endoscopic healing and substantial relieve of symptoms), there are no major differences between the different PPIs. However in relation to the relief of the symptoms, they may have different behaviour as we will discuss on below.
PPIs should be administered (standard doses, once a day 30-60 min before the first meal of the day) for maximal pH control.
What are the main hurdles to overcome when developing a treatment for erosive GERD?
The medical management of GERD involves the administration of PPIs, but the patient’s response to such treatment may vary: 20% - 40% may be considered “difficult to treat” as they show no significant results to the initial treatment with PPIs.
There are several possibilities that may explain the difficulty to treat such patients: lack of adherence to the pharmacological treatment, genotype differences that confers altered capacity to metabolize PPIs, non-acid gastroesophageal reflux, etc.
In chronic users of PPIs, the chronic elevation of seric gastrin and the bacterial overgrowth in the stomach (as consequence of the reduction of the gastric acid barrier) should be considered.
PPIs therapy can be a risk factor for Clostridium difficile infection and should be used with care in patients at risk.
Please can you outline the recent PAMES study?
The objective of the study was to compare the efficacy of pantoprazole-Mg and esomeprazole in GERD.
Patients with erosive GERD (Los Angeles grades A-D) were randomized to 4 weeks with pantoprazole-Mg (n=290) or esomeprazole (N=288) both 40 mg/day in a Brazilian multicentre (14 sites in 9 cities), double-blind study, with an additional 4 weeks’s treatment in non-responsive patients. Due to its subjectivity GERD-related symptoms were assessed with a validated self-assessment questionnaire (ReQuest-GI).
The primary end point was the proportion of patients in complete remission (significant relief of symptoms and confirmed endoscopic healing) at week 4. Secondary end point was the proportion in complete remission observed in week 8 for the patients that haven’t achieved complete remission at week 4.
What were the main results of this study?
Complete remission occurred in 61% of patients in each treatment group at 4 weeks and in 81% and 79% of patients in the pantoprazole-Mg and esomeprazole groups at 8 weeks, with no significant differences. Mucosal healing rates were high and not significantly different. At 8 weeks, symptom relief with pantoprazole-Mg was significantly greater than that with esomeprazole (91.6% vs. 86.0%, P=0.0370) because of continuous improvement in symptoms with pantoprazole-Mg from week 4 to week 8 (P=0.0206).
It has been concluded that pantoprazole-Mg 40 mg was as effective as esomeprazole 40 mg for the complete remission and the mucosal healing rate was high. However, symptom relief with pantoprazole-Mg continued to improve from 4 to 8 weeks and was greater than that with esomeprazole at week 8, suggesting an extended period of treatment effect.
What are your further research plans?
Some interesting protocols on GERD are being conducted in our centre such as the role of the behavioural measures in the treatment, new pharmacological approaches, etc.
Some functional disorders (particularly functional dyspepsia and irritable bowel syndrome) are also in our focus as well as the treatment and different aspects of the Helicobacter pylori infection.
What do you think the future holds for erosive GERD treatments?
The use of baclofen and its similar is perhaps an alternative for refractory to PPIs GERD patients. Baclofen is a GABA-b agonist and has been demonstrated to be effective in GERD by its ability to reduce the transient lower oesophageal sphincter relaxations and the reflux episodes.
However the usage of such kind of drugs is limited by side effects of somnolence, dizziness and intestinal constipation. Further, there has not been long-term data published regarding efficacy of Baclofen in GERD. Other products are also in preliminary analysis.
Where can readers find more information?
Katz PO, Gerson LB, Vela M. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2012; 108:308-328.
Cury MS, Ferrari AP, Ciconelli R, Moraes-Filho JP. Evaluation of health-related of life in gastroesophageal reflux disease patients before and after treatment with pantoprazole, Dis Esophagus 2006; 19:289-293.
Moraes-Filho JP, Pedroso M, Quigley EMM & PAMES study group. Randomised clinical trial: daily pantoprazole magnesium 40 mg vs. esomeprazole 40 mg for gastro-oesophageal reflux disease, assessed by endoscopy and symptoms. Aliment Pharmacol Ther 2014; 39:47-56.
About Professor Joaquim Moraes-Filho
Doctorate in internal medicine/Gastroenterology and PhD by University of Sao Paulo Medical School.
Post-Doctorate by the University of London.
Associate Professor of University of São Paulo Medical School.
Five text books on gastroenterology published in Brazil.
Around 180 papers on GERD, Helicobacter pylori, irritable bowel syndrome, published in Brazil, USA, Europe.
Current main interest: GERD, functional digestive disorders (dyspepsia, irritable bowel, syndrome) and H.pylori .