Relationship Between Chloroquine or Hydroxychloroquine Use and Hearing Disorders: A Systematic Review and Meta-Analysis

Abstract

Background and Objectives: Chloroquine and its analog hydroxychloroquine are derivatives of 4-aminoquinoline and are regularly used in the treatment of malaria and autoimmune diseases. Among the side effects of these drugs, alterations associated with the auditory system are frequently mentioned. Thus, the aim of this systematic review is to systematically review publications on hearing disorders and chloroquine or hydroxychloroquine use.Materials and Methods: Inclusion criteria were observational or interventional studies on audiological assessment in participants who were using chloroquine or hydroxychloroquine. The methodological quality was independently assessed by two reviewers using the Meta-Analysis of Statistics: assessment and review Instrument. The certainty of the evidence was assessed using the GRADE tool.Results: A total of 1,372 non-duplicate papers were screened, out of which 17 were included in the final qualitative synthesis, and 5 studies in the meta-analysis. The odds ratio for the two subgroups evaluated did not show significance with no heterogeneity between the effects observed between the different diseases (I<sup>2</sup>=0%) and obtaining the global estimate of 0.76 (95% confidence interval [CI]=0.41–1.39; <i>p</i>>0.05). Despite the inclusion of papers with different disease samples, the heterogeneity observed in the analysis was low (I<sup>2</sup>= 0%) and prediction interval (95% PI=0.32–1.80; p>0.05) remained close to that estimated by the CI (95% CI=0.41–1.39; <i>p</i>>0.05). The certainty of the evidence assessed by the GRADE tool was considered very low due to the risk of bias, indirect evidence, and imprecision.Conclusions: The findings of this study suggest that the use of chloroquine/hydroxychloroquine is not associated with hearing disorders.