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Immune checkpoint inhibitor-associated capillary leak syndrome: A systematic review and a worldwide pharmacovigilance
Jonathan Wong So1,2, Fatma Bouibede1, Annie-Pierre Jonville-Béra3
1CHR d'Orléans, Service de Médecine Interne, Orléans, France.
Insights
Immune checkpoint inhibitors (ICIs) are linked to capillary leak syndrome (CLS), with a significant safety signal found. ICI-induced CLS presents a distinct clinical profile compared to the idiopathic form.
Area of Science:
- Pharmacovigilance
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) have been anecdotally linked to capillary leak syndrome (CLS).
- This study aimed to characterize ICI-induced CLS and evaluate its safety signal.
Approach:
- A systematic review of literature and a global disproportionality analysis of the World Health Organization pharmacovigilance database were conducted.
- The study analyzed 47 cases of ICI-associated CLS reported up to January 15, 2023.
Key Points:
- A significant signal of disproportionate reporting for CLS with ICIs was identified.
- The median time to CLS onset was 12 weeks, with 57% of patients experiencing prior immune-related adverse events.
- Fatal outcomes were reported in 23% of cases.
Conclusions:
- ICI-induced CLS exhibits a distinct clinical presentation, including a prolonged onset time, compared to idiopathic CLS.
- The findings confirm a significant safety concern for CLS associated with immune checkpoint inhibitors.
Background:
Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI-induced CLS through a systematic review and to assess a potential safety signal.
Methods:
Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0.
Results:
A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8).
Conclusion:
This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.
