Immune checkpoint inhibitors increase the risk of neurological toxicities

The following article is part of the conference coverage of the American Academy of Neurology (AAN) 2021 Annual Virtual Meeting. The Neurology Advisor staff will provide breaking news related to research by leading experts in neurology. Check out the latest news from the AAN 2021 virtual annual meeting again.

Treatment with immune checkpoint inhibitors (ICIs) is associated with an increased risk of neurological toxicities, with the combined use of ICIs carrying a higher risk of some neurological complications compared to monotherapy. This is based on research to be presented at the American Academy of Neurology’s 2021 Virtual Annual meeting April 17-22, 2021.

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The retrospective observational study was based on data from the FAERS database collected from 2014 to 2019. Investigators looked at the rate of ICI-related adverse events (AEs), defined as adverse reactions reported in patients treated with anti-PD-1 (nivolumab and pembrolizumab), anti-PD-L1 (atezolizumab, avelumab and durvalumab) and anti-CTLA-4 (ipilimumab and tremelimumab).

In addition, in the disproportionality analysis, the study’s investigators rated the neurological side effects previously reported to be associated with ICIs.

In the 50,406 reports of ICI-related adverse reactions, a total of 3619 neurological cases were found.

There were 1985 neurological AEs with anti-PD-1, which accounted for 6.10% of anti-PD-1-related AEs, and 372 neurological AEs with anti-PD-L1, which accounted for 5.26% of anti-PD-L1 made out. related UE. A total of 366 neurological side effects with anti-CTLA-4 or 12.7% of anti-CTLA-4 related side effects and 896 with a combination of anti-CTLA-4 with anti-PD-1 or anti-PD- were reported. L1 (11.3% of the combined ICI-related side effects).

Compared to non-ICI drug use, treatment with ICI was associated with an increased risk of neurological complications, including hypophysitis or hypopituitarism (reporting odds ratio) [ROR]207.14; 95% CI, 176.44-243.19]), myasthenia gravis (MMR, 23.28; 95% CI, 20.28-26.73), vasculitis (MMR, 1.49; 95% CI, 1, 20-1.84), neuropathy (MMR, 1.08; 95% CI 1.02-1.15), Guillain-Barre syndrome (ROR 5.15; 95% CI 3.97-6.70), Meningitis (ROR 5.71; 95% CI 4.75-6.86) and encephalitis or myelitis (ROR 14.15; 95% CI, 12.59-15.91).

In contrast, ICU treatment was associated with a reduced risk of demyelinating disorders (ROR, 0.51; 95% CI, 0.41–0.63).

The combined use of ICIs correlated with a higher risk of hypopituitarism, hypophysitis, neuropathy, Guillain-Barre syndrome, meningitis, encephalitis and myelitis compared to monotherapy. Despite this increased risk, the investigators found that “the proportion of serious neurological events related to combination therapy has declined in recent years”.


Mikami T., Liaw B., Asada M. et al. Neuroimmunological adverse events related to the immune checkpoint inhibitor: a retrospective pharmacovigilance study using the FAERS database. J Neurooncol. 2021; 152 (1): 135-1. 144. doi: 10.1007 / s11060-020-03687-2

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