Facial palsy induced by immune checkpoint blockade: A systematic analysis of clinical trials and a pharmacovigilance study of postmarketing data

To estimate the risk of facial nerve palsy (FP) associated with immune checkpoint inhibitors (ICIs), and to describe its clinical features. Data from randomized controlled trials (RCTs) and FDA Adverse Event Reporting System (FAERS) database were included. The primary outcome was the risk of FP events associated with ICIs. For data from RCTs, pooled analysis was performed by using risk ratios (RRs) with 95%CIs. In a separate retrospective pharmacovigilance study of FAERS, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). A total of 21 RCTs (193,05 patients) were included, ICIs were associated with increased risk of FP (OR = 3.07, 95%CI:1.43–6.58). Results of subgroup analysis indicated that OR of ICI-related FP did not vary significantly by tumor type, ICIs treatment schedule, case of events, study design, median PFS and publication status. FAERS pharmacovigilance data identified 274 cases of FP related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of FP (ROR = 3.03, 95%CI:2.69–3.42; IC = 1.56, 95%CI:1.38–1.76). The median onset time of FP was 5.5 weeks, drug interruption was recorded in 78.0% of cases, with a positive dechallenge in 82.8 % of cases, and 71.7% of cases were recovered or recovering. These data suggest that ICIs were significantly associated with increased risk of FP in both trial settings and in clinical practice.