Immune Checkpoint Inhibitors and Venous Thromboembolism: An Analysis of the WHO Pharmacovigilance Database

Abstract

Data on venous thromboembolic events (VTEs) in patients receiving immune checkpoint inhibitors (ICIs) are scarce and conflicting. This study investigated the risk of reporting VTEs associated with ICIs in comparison with all other anticancer drugs. The World Health Organization pharmacovigilance database (VigiBase), comprising >30 million individual case safety reports, was queried. All reports on patients with cancer, involving at least one anticancer drug as a suspect or interacting drug and registered from January 1, 2008, to May 31, 2021, were included. The association between ICIs and the risk of reporting VTEs was estimated using the reporting odds ratio (ROR) as a measure of disproportionality with all other anticancer drugs as comparators. RORs were estimated as crude and adjusted RORs for age, sex, and other medications (excluding anticancer drugs) associated with risk of VTEs. Among 1,196 patients experiencing VTEs after ICI treatment, the median age was 65 years and 57.6% were men. Anti‐PD‐1 agents (62.5%) were the most frequently reported. ICIs were not associated with higher reporting of VTEs when compared with other anticancer drugs (crude ROR 0.63, 95% confidence interval (CI) 0.60 to 0.67 and adjusted ROR 0.70, 95% CI 0.65–0.74). No signal of disproportionate reporting was found when considering each class of ICIs. In conclusion, ICIs were not associated with higher reporting of VTEs, in comparison with all other anticancer drugs in a large‐scale pharmacovigilance database. Owing to the limitations inherent to pharmacovigilance studies, prospective studies, including an adequate comparison group, are needed to assess the risk of VTEs in ICI‐treated patients.

Burden of Cardiovascular Disease in Immune Checkpoint Inhibitor–Treated Patients

“…Given the observational nature of this study and the overall small number of CV events, we are not able to draw connections between whether the use of ICIs led to CV events like VTE and ischemia. Interestingly, through analysis of the World Health Organization pharmacovigilance database, Allouchery et al 18 found that ICIs did not correlate with higher reporting of VTEs compared with other anticancer drugs. In contrast, Drobni et al 19 showed that atherosclerotic cardiovascular events increased after ICI initiation as did atherosclerosis on imaging.…”