Fexuprazan and Esomeprazole in Patients with Disorders Associated with Acid Reflux: A Comprehensive Review and Meta-Analysis of Randomized Controlled Trials

<b>Background</b>: This investigation compared the efficacy and safety of fexuprazan 40 mg and esomeprazole 40 mg in patients with acid reflux-related disorders, including erosive esophagitis (EE) and laryngopharyngeal reflux disease (LPRD). <b>Methods</b>: A systematic search was conducted across five databases until January 2025. Primary outcomes included esophageal lesion healing, complete resolution of symptoms (CRS), and 24 h symptom-free days. Meta-analyses used random-effects models with the inverse variance method. The Risk of Bias 2.0 tool and the certainty of evidence (CoE) using GRADE methodology were assessed. <b>Results</b>: Three randomized controlled trials (n = 695) conducted in Asian countries were included. Fexuprazan may have little to no effect compared to esomeprazole on EE healing rate at 4 weeks (RR 1.02, 95% CI 0.93 to 1.12, I² = 0%, n = 2 studies, CoE very low) and 8 weeks. No significant differences were found between treatments regarding CRS at 1 week (RR 1.29; 95% CI: 0.84 to 1.99; I² = 0%; n = 2 studies; CoE very low) and 8 weeks, or in the 24 h symptom-free days at 1 week (MD 2.67 days, 95% CI -2.76 to 8.10, I² = 41%, n = 2 studies, CoE very low) and 8 weeks. Fexuprazan also showed little to no effect on treatment-emergent adverse events (RR 1.00, 95% CI 0.83 to 1.20, I² = 0%, n = 3 studies, CoE very low). Nonetheless, the evidence for all outcomes was rated as very uncertain. <b>Conclusions</b>: Fexuprazan 40 mg may provide similar efficacy compared to esomeprazole 40 mg in EE, with a comparable safety profile to esomeprazole in EE and LPRD patients. However, the evidence is highly uncertain, requiring further studies.