Effect of Proton Pump Inhibitors on Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) in Patients with Laryngopharyngeal Reflux: A Systematic Review and Meta-Analysis

ABSTRACT Objectives: The purpose of this study was to determine the efficacy of proton pump inhibitor (PPI) therapy in treating the symptoms and laryngeal findings of laryngopharyngeal reflux (LPR). Methods: Placebo-controlled, randomized clinical trials published after June 2001 to January 2021 which used PPI as the sole intervention and the RSI or RFS as outcome measures were eligible for inclusion. Studies that were published prior to June 2001, those which only made use of questionnaires other than the RSI or RFS, those which used PPI in combination with other treatments, or those with unavailable full-text manuscripts were excluded. These studies were identified from MEDLINE, Scopus, Cochrane Library, Embase, and HERDIN Plus databases which were searched from May 21 to 26, 2020. The primary outcome was the mean difference between baseline/pre-treatment and post-treatment RSI scores for both PPI and placebo groups. The secondary outcome was the mean difference between pre-treatment and post-treatment RFS scores for PPI and placebo groups. Aggregate results of these outcomes were analyzed using forest plots. Heterogeneity was determined through prediction intervals. Risk of bias of individual studies was assessed using the Cochrane Collaboration’s Tool in Assessing Risk of Bias.   Results: Nine randomized control trials were included with a total of 737 patients randomized and 595 patients analyzed – 294 from the PPI group and 301 from the placebo group. There were notable variations among the studies in terms of choice of PPI, dosage and frequency. Out of nine studies, four used both RSI and RFS in their analysis. Two studies used RSI alone and three used the RFS in combination with symptom questionnaires other than the RSI. There was a significant decrease in the RSI of the PPI group versus the placebo group with a mean difference of -2.83 (95% CI, -5.13 to -0.53, p = .02). However, there was no significant decrease in the RFS between PPI and placebo groups with a mean difference of -0.84 (95% CI, -2.66 to 0.98, p = .37). For two clinical trials which only reported post-treatment RFS, there was also no significant difference between the two treatment groups with a mean difference of 1.27 (95% CI, -0.22 to 2.76, p = .10). Conclusion: This meta-analysis found that, although a statistically significant benefit in RSI was noted with PPI therapy, this difference may not translate to a clinically significant change in symptoms; therefore, there is insufficient evidence to recommend for or against the treatment of LPR with PPIs.