We greatly appreciate the interest in the fifth Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection shown by Valdovinos-Díaz et al., as well as their valuable observations on the potential role of rebamipide as an adjuvant therapy in H. pylori eradication regimens.1

Rebamipide is a drug whose discovery and pharmacologic characterization date back to 1987, when Yamasaki et al. first described its gastroprotective properties in experimental models.2 Thirty-eight years have passed since that initial finding, and during the ensuing period, a solid, robust body of scientific evidence has been produced. At present, there are 661 articles indexed in PubMed related to rebamipide, most of which focus on its role as a gastric mucosal protective agent and in gastritis management. Of particular relevance to the discussion at hand is the fact that 88 of those publications have specifically explored the effect of rebamipide in the context of H. pylori infection. The first of those studies was by Suzuki et al., published in 1994, who demonstrated that rebamipide attenuated the H. pylori-induced damage to gastric mucosal cells that was associated with neutrophil-derived oxidants.3 That pioneer work laid the groundwork for understanding the mechanisms through which rebamipide could contribute, not only to protection of the mucosa, but also to modulation of the inflammatory response associated with the infection. Subsequent mechanistic studies have contributed a solid biologic rationale for the possible benefit of rebamipide in H. pylori infection. Rebamipide has been reported to reduce proinflammatory cytokines and modulate the reactive oxygen species system in the infected gastric mucosa,4 and other studies have shown that it inhibits the adhesion of H. pylori to gastric epithelial cells.5 Those anti-inflammatory and anti-adhesive effects could contribute to the improved clinical results observed when the drug is used as an adjuvant therapy.

We completely agree with the analysis presented by the authors regarding the available international evidence. The meta-analyses cited, particularly that of Andreev et al., which included 1,227 patients,6 consistently showed a benefit in eradication rates when rebamipide was added to different therapeutic regimens —especially in combination with dual therapies—, with an approximate absolute increase of 8.7% and a favorable safety profile. In addition, its cytoprotective mechanism of action, with no direct antibiotic activity, is a relevant strategic advantage in the current context of growing antimicrobial resistance.

Even though the comments by Valdovinos-Díaz et al. are particularly timely, it should be clarified that during the preparation of the consensus and its review process, rebamipide was not yet available in Mexico, which is why it was not included in the final recommendations. Nevertheless, we fully agree that its recent availability in our country comes at an especially appropriate time, when innovative therapeutic regimens are being explored that include potassium-competitive acid blockers (PCABs) and dual therapies. Said timing presents a unique opportunity for evaluating the role of rebamipide within the new therapeutic strategies that are transforming the approach to H. pylori infection.

We believe that producing our own evidence with this drug in the Mexican population is indispensable, as is evaluating the following key points:

• a)

  Identifying the therapeutic regimen(s) in which rebamipide could serve as an adjuvant for H. pylori eradication in Mexico.

• b)

  Evaluating its possible effect on the prevention of H. pylori reinfection, when used after successful eradication.

• c)

  Analyzing its cost-benefit ratio in the context of the Mexican healthcare system.

• d)

  Determining its impact on tolerability and adherence to eradication regimens, considering that the improvement of treatment-associated gastrointestinal symptoms could significantly influence the therapeutic results.

• e)

  Exploring its possible benefit in specific patient subgroups, such as those with atrophic gastritis, intestinal metaplasia, a history of failed eradication, or persistent dyspepsia after eradication.

In this regard, we strongly encourage interested research groups to develop study protocols that address these relevant clinical questions. Interinstitutional collaboration, methodological standardization, and the continuity of research networks —such as the Mexican Registry for the Study of H. pylori— are essential for producing high-quality evidence that can be translated into tangible and measurable benefits for our patients.

The letter submitted by Valdovinos-Díaz et al. is a valuable contribution to the scientific debate on the optimal management of H. pylori in Mexico. Commentary such as theirs enriches collective knowledge, stimulates research, and encourages us to keep our recommendations updated, based on the best available evidence and the specific needs of our population. Accordingly, we take note of their proposal and formally commit to considering the inclusion of rebamipide in the next update of the Mexican Consensus on Helicobacter pylori.