Drug-associated central nervous system vasculitis and reversible cerebral vasoconstriction syndrome: A global disproportionality analysis of the WHO pharmacovigilance database (VigiBase).

AIMS: This study aimed to identify and characterize drugs disproportionately associated with central nervous system vasculitis (CNSV) and reversible cerebral vasoconstriction syndrome (RCVS) in VigiBase, the World Health Organization (WHO) global pharmacovigilance database, and to describe their pharmacological and temporal profiles.

METHODS

We conducted a case-non-case study in VigiBase, the WHO global pharmacovigilance database (extract June 2025). Both unadjusted and adjusted reporting odds ratios (aROR) were estimated, the latter using multivariate logistic regression accounting for age, sex, geographic region and reporting characteristics. Time-to-onset, dechallenge outcomes and fatality rates were also analysed.

RESULTS

We identified 735 CNSV cases and 1553 RCVS cases. CNSV was predominantly associated with immune checkpoint inhibitors (pembrolizumab and nivolumab) and antithyroid drugs (propylthiouracil), with a median time-to-onset of 35.50 days (interquartile range [IQR] 7.75-123.25). RCVS was primarily associated with serotonergic and vasoactive agents (triptans, ergot derivatives, selective serotonin reuptake inhibitors [SSRIs] and cannabis), with a markedly shorter onset of 8.75 days (IQR 3.25-52.88). The strongest RCVS signal was a novel association with teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor approved for thyroid eye disease (6 cases; aROR 60.17, 95% confidence interval [CI] 18.66-194.05). Female sex was independently associated with RCVS (aROR 2.57, 95% CI 2.23-2.97).

CONCLUSIONS

Drug-associated CNSV and RCVS exhibit distinct pharmacological and temporal profiles, which may help inform drug withdrawal decisions and optimal management of these neurovascular emergencies.