Do peripheral neuropathies differ among immune checkpoint inhibitors? Reports from the European post-marketing surveillance database in the past 10 years

Abstract

Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs.

Real-World Safety Data of the Orphan Drug Onasemnogene Abeparvovec (Zolgensma®) for the SMA Rare Disease: A Pharmacovigilance Study Based on the EMA Adverse Event Reporting System

“…Our study aimed to describe the Zolgensma ® safety profile emerging from a real-world context by analyzing data collected in the European pharmacovigilance database. Our choice was based on the consideration that, even if pre-marketing clinical trials allow the acquisition of the majority of important drug-safety data, only use in a real-world context can better define the safety aspects, allowing for the identification of rarer ADRs [ 15 , 16 , 17 , 18 ]. For these reasons, continuous post-marketing monitoring of drug safety is essential.…”

Guillain-Barré syndrome and checkpoint inhibitor therapy: insights from pharmacovigilance data

“…These events encompass a spectrum of neuromuscular complications that can occur as unintended consequences of checkpoint inhibitor therapy, ranging from mild and reversible symptoms to severe and potentially life-threatening conditions. [1][2][3] Guillain-Barré syndrome (GBS) is a rare neurological disorder characterised by the immune system's misguided attack on the peripheral nerves, resulting in muscle weakness and paralysis and is the most common cause of flaccid paralysis worldwide. 4 5 The link between checkpoint inhibitors and the development of GBS has been described in case reports.…”

Neurological adverse events associated with PD-1/PD-L1 immune checkpoint inhibitors

“…Current literature is primarily based on case reports and retrospective cohort studies, with a low level of evidence, requiring mechanistic studies and prospective interventions for confirmation ( Seligman et al, 2022 ). Additionally, Guillain-Barré syndrome ( Kao et al, 2018 ; Rajendram et al, 2021 ), chronic inflammatory demyelinating polyneuropathy, and mononeuropathies ( Larkin et al, 2017 ; Ruggiero et al, 2023 ) have also been reported in clinical applications.…”