Advances in the pharmacotherapeutic management of refractory peptic ulcers

ABSTRACT

Introduction

Refractory peptic ulcer is now a rare disease since most peptic ulcers heal with appropriate treatment with proton pump inhibitors (PPIs) and/or Helicobacter pylori eradication.

Areas covered

The most frequent cause of apparent refractoriness is lack of adherence to treatment. Persistence of H. pylori infection, use or abuse (often surreptitious) of high dose non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin (ASA) are the two major causes of true refractory ulcers. There is a growing number of peptic ulcers which are not linked to either NSAIDs or H. pylori infection. Refractoriness in these ulcers can be linked to gastric acid hypersecretion, rapid PPI metabolization, ischemia, chemo-radiotherapy, immune diseases, more rarely to other drugs or be fully idiopathic. Treatment of the cause of the ulcer, if known, is essential. This review is based on pertinent publications retrieved by a selective search in PubMed, with particular attention to refractory peptic ulcer.

Expert opinion

High-dose PPI or the new potassium competitive acid blocker or the combination of PPIs with misoprostol can be recommended in these cases. Other more experimental treatments such the topical application of platelet-rich plasma or mesenchymal stem cells have also been suggested. Surgery is the last option, but there is no guarantee of success, especially in NSAID or ASA abusers.

KEYWORDS:

• Peptic ulcer
• refractory peptic ulcer
• Helicobacter pylori
• non-steroidal anti-inflammatory drugs (NSAIDs)
• aspirin (ASA)

Article highlights

• Refractory peptic ulcers are now a rare entity if treated appropriately, but at the same time, they represent an enormous challenge in clinical practice.

• When facing patients with refractory peptic ulcer, adherence to treatment must be checked (PPI and/or H. pylori eradication) because it is the main cause of ”false” refractory peptic ulcer.

• NSAIDs or high doses of ASA have been pointed out as the main causes of ulcer refractoriness. Sometimes their consumption is surreptitious.

• Refractory peptic ulcers which are not associated with H. pylori or NSAID/ASA use may be due to a diverse number of potential causes that need to be identified. Some of these causes include use of other drugs (biphosphonates, clopidogrel or chemotherapeutic agents), gastric acid hypersecretion, anastomotic ulcers after bariatric surgery or ischemic ulcers. The identification of factors that determine ulcer refractoriness is essential to make a rational approach to treatment.

• When a reason to explain peptic ulcer refractoriness is not found, different therapeutic approaches can be followed. Increasing the dose of the PPI, prescription of the new potassium competitive acid blocker or the combination of these acid antisecretory drugs with misoprostol can be a rational approach.

• New therapies like the use of growth factors or the use of stem cells have been tested in experimental animal models of NSAID induced gastric ulcers showing very promising results, but they can be regarded as still experimental.

• Surgery must be the last option since there is no guarantee of therapeutic success, especially if NSAID or ASA abuse is the cause.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.