Title:Assessment of Neurologic Safety Profile of Immune Checkpoint Inhibitors:
Evaluation of Adverse Drug Reaction Reports
Volume: 19
Issue: 3
Author(s): Atul Khurana, Harikesh Dubey and Mandeep Kumar Arora*
Affiliation:
- School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun, India
Keywords:
Immune checkpoint inhibitors, neurologic safety, european medicine agency, eudravigilance, WHO, vigiaccess.
Abstract:
Background: Immune checkpoint inhibitors (ICIs) used in immunotherapy have revolutionized
cancer management. However, ICI therapy can come with serious neurologic risks.
Objective: The objective of our study is to analyze the occurrence of neurologic events with ICIs.
Methods: We referred to EudraVigilance (EV) and VigiAccess to evaluate the frequency of individual
case safety reports (ICSRs), including neurologic events with ICIs. Data was gathered for
a period from the date of ICI’s marketing authorization till 30 January 2023. The computational
assessment was conducted with the help of reporting odds ratio (ROR) and its 95% confidence
interval (CI).
Results: Overall, 8181 ICSRs in EV and 15905 ICSRs from VigiAccess were retrieved for neurologic
events, with at least one ICI as the suspected drug. The majority of the ICSRs were reported
for nivolumab, pembrolizumab, and ipilimumab, whereas frequently reported events were neuropathy
peripheral, myasthenia gravis, seizure, Guillain-Barre syndrome, paraesthesia, syncope,
encephalopathy, somnolence. Under EV, 92% of ICSRs were reported as serious, 10% included
fatal outcomes, and nearly 61% cited patient recovery. Atezolizumab (ROR 1.64, 95% CI 1.75-
1.52), cemiplimab (ROR 1.61, 95% CI 1.98-1.3), and nivolumab (ROR 1.38, 95% CI 1.44-1.31)
had a considerable increase in the frequency of ICSR reporting. Cerebrovascular accident, posterior
reversible encephalopathy syndrome, tremor, and somnolence were identified as potential
signals.
Conclusion: ICIs were significantly associated with neurologic risks, which cannot be generalized.
A considerable increase in ICSR reporting frequency was observed with atezolizumab,
cemiplimab, and nivolumab, while avelumab, pembrolizumab, durvalumab, and cemiplimab were
linked with four potential signals. These findings suggest the consideration of a revision of the
neurologic safety profile of ICIs. Furthermore, the necessity for additional ad-hoc research is
emphasized.
