Table 2.
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 ICSRs | Overall 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 monotherapy | ROR and 95% CI [,] combination ICIs vs monotherapy | ROR 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 dysfunction | 197 (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 myelitis | 186 (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 syndrome | 64 (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 meningitis | 36 (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