Effects of Intratympanic Gentamicin and Intratympanic Glucocorticoids in Ménière’s Disease: A Network Meta-Analysis of Randomized, Controlled Trials

Backgroud: Controversies exist in choosing Intratympanic gentamicin or intratympanic glucocorticoids for Meniere’s disease. Methods: To assess the treatment effects and safety among intratympanic gentamicin, glucocorticoids and placebo therapy in Meniere disease. Electronic searches in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, MEDLINE, BIOSIS Previews, Embase, CINAHL, ClinicalTrials.gov and the European Union Clinical Trials Register were conducted from inception until March 2019. All randomized controlled trials of intratympanic gentamicin or glucocorticoids for Meniere’s disease, compared with each other or placebo therapy, were considered for this review. Two independent reviewers extracted study data and performed quality assessment using the Cochrane Risk of Bias Tool. Network meta-analysis on vertigo control, function level scales (FLS), hearing outcomes and tinnitus handicap inventory (THI) were calculated with a Bayesian approach using the R package netmeta (version:3.5.2). The quality of primary outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings: 10 studies of RCTs (455 patients) met inclusion criteria as described. Pooled results indicated significant advantage of intratympanic gentamicin and glucocorticoids over placebo treatments in vertigo control (gentamicin vs placebo: risk rate, RR, 2.56; 95%CI, 1.18 to 5.54; glucocorticoids vs placebo: RR, 3.02; 95%CI, 1.36 to 6.73). The comparison between gentamicin and glucocorticoids did not show a statistically significant result (RR 0.85; 95%CI, 0.69 to 1.03). FLS also showed improvements in intratympanic therapies over placebo. For PTA and SDS, intratympanic glucocorticoids showed better hearing protective results than gentamicin (change of PTA, MD, -6.48 dB; 95%CI, -11.84 dB to -1.13 dB; change of SDS, MD 7.69%; 95%CI, 0.83% to 14.55%),but no statistical significance in comparisons with placebo. No difference was found in THI among three approaches. Interpretation: Intratympanic gentamicin and glucocorticoids are two effective approaches to control vertigo symptoms for Meniere’s disease. Compared with gentamicin, glucocorticoids showed a potentially better hearing protective role, and intratympanic gentamicin therapy was not associated with high risk of hearing loss than placebo. Funding Statement: The authors have no funding to disclose. Declaration of Interests: The authors have no financial relationships, or conflicts of interest to disclose. Ethics Approval Statement: This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions, and the PRISMA extension statement for reporting of systematic reviews incorporating NMA of health care interventions. The pre-specified protocol of this systematic review has been registered in November 2018 (PROSPERO Identifier: CRD42018114389).