Selected neurological adverse events (detected as signals) reported for ICIs versus the full database from VigiBase, from Jan 1, 2008, to September 28, 2018

Total number of ICSRsOverall ICIs (n:)Full database (full; starting 2008a; N:14,627,365)ROR and 95% CI [,] anti-PD-1 or anti-PD-L1 vs anti-CTLA-4 monotherapyROR and 95% CI [,] combination ICIs vs monotherapyROR and 95% CI [,] ICIs vs full database
MONO (N:43,960)COMB (N:4693)
MONO-PD1 (N:34,401)MONO-CTLA4 (N:9559)
Number of ICSRs by Neuro-ADR subgroup
 Neuromuscular junction dysfunction197 (0.57%)14 (0.15%)17 (0.36%)4380 (0.03%)3.9 [2.3–6.8]0.8 [0.5–1.2]16.5 [14.5–18.9]
 Non-infectious encephalitis and/or myelitis186 (0.54%)21 (0.22%)43 (0.92%)7460 (0.05%)2.5 [1.6–3.9]2 [1.4–2.7]10.4 [9.2–11.8]
 Guillain-Barre syndrome64 (0.19%)37 (0.39%)21 (0.45%)7962 (0.05%)0.48 [0.32–0.72]2 [1.2–3.1]4.7 [3.9–5.6]
 Non-infectious meningitis36 (0.10%)20 (0.21%)16 (0.34%)6986 (0.04%)0.5 [0.29–0.86]2.7 [1.5–4.7]3.1 [2.5–3.9]

Abbreviations: Mono monotherapy, COMB combination therapy, PD1 Programmed death-1/ligand-1, CTLA4 cytotoxic T lymphocyte antigen-4

Data are N (%) unless otherwise stated. ICIs refers to any ICSR reported for treatment with nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, ipilimumab, or tremelimumab. Anti-PD-1 or anti-PD-L1 monotherapy refers to any ICSR associated with any of the following five drugs only when used alone: nivolumab, pembrolizumab, atezolizumab, avelumab, or durvalumab. Anti-CTLA-4 monotherapy refers to any ICSR associated with ipilimumab or tremelimumab alone. Combination ICIs refers to any ICSR reported with at least one anti-PD-1 or anti-PD-L1 drug combined with an anti-CTLA-4 drug. ICSRs = individual case safety reports. ICIs = immune checkpoint inhibitors. ROR = reporting odds ratio

aFirst reports of ICSRs associated with ICIs started in 2008

Bold text denotes statistically significant differences