Next step for antireflux mucosal ablation

10.1055/a-2740-9297

Over the past 25 years, several endoscopic antireflux devices have been introduced, but have usually been withdrawn a few years later because of disappointing efficacy, severe complications, or both [1]. These devices can be roughly divided into three different categories: endoscopic injection of barrier reinforcements at the lower esophageal sphincter (LES) level (Gatekeeper, Enteryx); endoscopic suturing techniques (Esophyx/TIF, Endocinch, MUSE, Overstitch); and techniques that alter the gastroesophageal junction (GEJ) by creating fibrosis (Stretta). Most of these innovations were driven by industry and included complex equipment to enhance the antireflux barrier. What the techniques also have in common is that most studies consisted of open-label prospective case series with relatively short follow-up and soft primary end points, such as reduction in proton pump inhibitor (PPI) use. It is no surprise that these studies usually presented favorable first results, which then led to disappointment in subsequent clinical use or better designed controlled studies, or to the devices being withdrawn after serious complications.

Antireflux mucosectomy (ARMS) was introduced as a technique that used endoscopic mucosal resection (EMR) in the cardia to induce fibrosis and change the shape of the GEJ [2]. It differed from the previously mentioned endoscopic antireflux techniques as it was introduced by academic endoscopists and does not require expensive dedicated equipment. Antireflux mucosal ablation (ARMA) is quite similar to ARMS, but uses argon plasma coagulation instead of EMR to induce scarring around the cardia [3].

“... it is surprising that a reflux-reducing treatment such as ARMA provided symptomatic relief in patients with functional heartburn, as these are patients in whom there is no evidence at all that their symptoms are caused by gastroesophageal reflux.”

In contrast to other endoscopic antireflux techniques, ARMA seems relatively easy to perform and only standard endoscopic equipment is required; because of this it has more potential to change the treatment landscape. High quality studies of the technique were however lacking.

Chavan et al. are therefore to be congratulated for designing and performing the randomized sham-controlled trial with inclusion of relevant end points that is published in this issue of Endoscopy [4]. It is these kinds of studies that drive the field forward. An impressive result was seen on the primary end point of the study, the gastroesophageal reflux disease health-related quality-of-life (GERD-HRQL) score. Furthermore, acid exposure time, total number of reflux episodes, reflux esophagitis, Hill’s grading, and PPI use were all reduced in the patients undergoing ARMA. The broad improvement of reflux parameters not seen in the patients treated with a sham procedure suggests a real effect. Is ARMA therefore ready for widespread dissemination in clinical practice?

The most relevant question would be, for which kind of patients would this treatment be suited? The results of this trial showed that the acid exposure time was reduced from 3.0% to 2.2% and acid reflux episodes were reduced from 78 to 35 per 24 hours, which is a clear improvement but rather modest compared with the magnitude of effect that PPIs have on acid reflux. Most patients with GERD therefore seem to be better off with a PPI. However, while PPIs change only the acidity of the reflux episodes, ARMA also reduces the number of nonacid reflux episodes, resulting in a reduction in the total number of reflux episodes (from 102 to 45 / 24 hours). ARMA could therefore be beneficial for those patients who have an inadequate response to PPIs due to symptoms resulting from persistent nonacid reflux. Compared with a fundoplication, which reduces the number of reflux episodes from 90 to 7 per 24 hours, these results are however modest [5]. Also, ARMA does not restore a hiatal hernia, which also excludes most patients with severe GERD. For those patients with more severe GERD, antireflux surgery therefore remains more appropriate, but there is a subgroup of patients that have persistent symptoms on PPIs and are not willing or not eligible to undergo antireflux surgery.

The authors indeed selected a very mild GERD phenotype, with a physiological acid exposure and mostly an absence of reflux esophagitis. Two-thirds of the patients fell into the category of reflux hypersensitivity and one-third had functional heartburn. Such patients often have a poor response to PPIs as their symptoms result in part from hypervigilance. In these patients, PPIs just take the acidic aspect of the reflux trigger away and a remaining sensation of gastric contents flowing into the esophagus is still present. The authors have demonstrated that ARMA could be beneficial in this subgroup. This is convenient as, despite the low acid exposure, these patients often experience their symptoms as very severe and are poor candidates for antireflux surgery owing to their higher chance of developing postoperative symptoms of gas-bloat and dysphagia.

On the other hand, it is surprising that a reflux-reducing treatment such as ARMA provided symptomatic relief in patients with functional heartburn, as these are patients in whom there is no evidence at all that their symptoms are caused by gastroesophageal reflux. Furthermore, ARMA seemed to result in a greater reduction in nonacid reflux than in acid reflux, which has not been seen in previous studies. An explanation for this seemingly selective antireflux behavior of the GEJ is not provided and cannot be explained by the reduction in transient LES relaxations seen with ARMS [6]. It is also not clear from the manuscript when and how patients were unblinded, or whether they could have become unblinded during the study as the symptomatic improvement was much larger than the objective improvements. Furthermore, GERD is a mild and chronic disease for which alternatives exist and long-term efficacy and safety data of any intervention is therefore required before its widespread implementation. Finally, this is a dynamic field with the introduction of new techniques following quickly, such as the recently reported antireflux mucoplasty (ARMP) technique [7]. It therefore begs the question which technique should become the preferred option.

In conclusion, in diseases in which symptoms are the main determinant and a substantial placebo effect is present, sham-controlled studies are indispensable to determine the effect of endoscopic interventions. Too often we have encountered positive data from uncontrolled series describing endoscopic interventions that have disappeared completely in a subsequent sham-controlled study [8]. With their current study, Chavan at al. have made a significant step in the right direction for ARMA.

Publication History

Article published online:
07 January 2026

• References

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