We have read with great interest the article, “The Fifth Mexican consensus on the diagnosis and treatment of Helicobacter pylori infection”, by Remes-Troche et al., recently published in this journal.1 We congratulate the panel of experts for their comprehensive update and for the effort to emit recommendations in accordance with the national epidemiologic context.

We would like to draw attention to an aspect that was not addressed in the document: the possible role of rebamipide as adjuvant therapy in Helicobacter pylori (H. pylori) eradication regimens, particularly now that this drug is available in Mexico.

Rebamipide is a gastric mucosal protective agent that increases endogenous prostaglandin and gastric mucus production, reduces oxidative stress and inflammatory cytokine production, and improves blood flow and mucosal repair.2,3 Experimental studies have also shown that it partially inhibits the adhesion of H. pylori to gastric epithelial cells without affecting bacterial viability, which could contribute to reducing colonization after eradication therapy.4

The clinical evidence on rebamipide in H. pylori infection has been shown in two meta-analyses of randomized controlled trials (RCTs) that evaluated its inclusion in eradication regimens. Nishizawa et al. analyzed six studies that included 611 patients infected with H. pylori and observed that supplementation with rebamipide increased the eradication rates of dual therapy with a proton pump inhibitor (PPI) and amoxicillin from 61.4% to 73.3% (per-protocol analysis), with an odds ratio (OR) of 1.74 (95% CI 1.19–2.53).5 In a subsequent meta-analysis of 11 trials (1227 patients), Andreev et al. reported that the addition of rebamipide to different eradication regimens significantly increased overall efficacy (OR 1.75; 95% CI 1.31–2.33), with eradication rates of 82.7%, compared with 74.0% without rebamipide. In the subgroup analysis, there was a more consistent benefit when rebamipide was added to dual regimens (OR 1.77; 95% CI 1.17–2.50). A favorable trend was also observed when associated with triple therapies, albeit evidence remains limited and did not reach statistical significance, mainly due to the small number of trials. There was no increase in adverse events in any of the cases, and given that rebamipide has no direct antibiotic activity, it has not been associated with the development of antimicrobial resistance.6

Interestingly, two RCTs have shown that rebamipide use after eradication regimens improves endoscopic healing of H. pylori-associated ulcers. Terano et al. compared rebamipide with placebo for 7 weeks in 301 Japanese patients with H. pylori-associated peptic ulcer, after an eradication regimen. They found that endoscopic healing of gastric ulcers was greater with rebamipide than with placebo, at 80.0% (104/130) versus 66.1% (82/124) (95% CI 3.1–24.7; p = 0.013).7 Song et al. compared healing rates of H. pylori-associated peptic ulcer with rebamipide versus omeprazole, after eradication therapy, in 132 Chinese and Korean patients, finding no difference in ulcer healing between the two groups (absolute difference –1.0%; 95% CI –10.7 to 8.7; p = 0.88).8 Those two RCTs show the usefulness of rebamipide in patients with established mucosal damage even after having achieved bacterial eradication.

Considering the elevated prevalence of H. pylori in Mexico and the growing rates of resistance to clarithromycin, metronidazole, and fluoroquinolones that drive the use of increasingly more complex regimens,1 the possibility of optimizing eradication while simultaneously favoring the resolution of inflammation and mucosal lesions with a drug that is now available and has a good safety profile, is especially appealing.

We recognize that determining the magnitude of benefit of rebamipide in the new regimens that use potassium competitive acid blockers (PCABs) requires more studies, and ideally, RCTs in Mexican patients. However, the consistency of the existing meta-analyses and clinical trials suggests that the inclusion of rebamipide as an adjuvant should be considered.

Given the abovementioned information, we propose that future updates of the Mexican consensus on H. pylori evaluate both the role of rebamipide as an adjuvant therapy in eradication regimens and its potential role in the post-eradication phase, for improving inflammation and gastric mucosal healing.