Addition of prokinetic therapy to a PPI in reflux diseases


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Sirs, We read with great interest the article by Miwa et al. concerning a double-blind randomised trial studying the efficacy of adding mosapride, a prokinetic agent, to a proton pump inhibitor (PPI) for the management of non-erosive reflux disease (NERD).1 Recently, we reported a double-blind placebo-controlled trial exploring the role of mosapride in erosive oesophagitis.2 Both trials demonstrated no difference in primary outcomes between patients receiving mosapride and those randomised to placebo, suggesting little benefit from the addition of mosapride to a PPI in reflux patients, both with and without mucosal erosions.

Based on data from these trials, can we conclusively refute any evidence for a benefit of prokinetic therapy in gastro-oesophageal reflex disease (GERD)? Both suggested that there are subgroups of patients for whom combination therapy may be more effective than PPI alone. In our study, 4 weeks of mosapride achieved a greater reduction in symptom scores in those with severe symptoms, whereas Miwa et al. found NERD patients with several baseline characteristics appeared to respond more favourably to mosapride than placebo. Unfortunately, small sample size, the use of symptom scores as the outcome measures, and per-protocol analysis preclude any firm conclusions being drawn from these subgroup analyses.

The trials by both Miwa et al. and our group, nevertheless, confirm the efficacy of PPI monotherapy in GERD patients,3 and highlight the potential importance of targeting specific subgroups who are more likely to be inadequately relieved by PPI alone when investigating the effect of adjuvant therapy in GERD patients. The recognition of these subgroups is particularly important among NERD patients, who may be more heterogeneous in pathophysiology.4

We suggest future research should focus on distinct subgroups of reflux patients with a low likelihood of satisfactory response to PPI, defined using non-invasive and clinically convenient parameters, in order to address the unmet needs of these patients.5


Declaration of personal and funding interests: None.