- Design
- Case–non-case disproportionality analysis, WHO VigiBase
- Population
- 1553 RCVS and 735 CNS vasculitis reports
- Primary outcome
- Adjusted reporting odds ratios by drug; time to onset
- Effect
- RCVS onset median 8.75 days; teprotumumab aROR 60.17 (18.66–194.05)
This case–non-case study of VigiBase, the WHO global pharmacovigilance database, examined 1553 reports of reversible cerebral vasoconstriction syndrome and 735 of central nervous system vasculitis, adjusting for age, sex, region and reporting characteristics. It was published in the British Journal of Clinical Pharmacology in September.
RCVS was mainly associated with triptans, ergot derivatives, SSRIs and cannabis, with median onset 8.75 days after exposure. The strongest RCVS signal was teprotumumab, used for thyroid eye disease (6 cases; adjusted reporting OR 60.17, 95% CI 18.66 to 194.05). Women were at higher risk (aROR 2.57). CNS vasculitis was associated mainly with pembrolizumab, nivolumab and propylthiouracil, with median onset around five weeks.
The two patterns point to different questions at the bedside. Sudden headache within days of starting a serotonergic or vasoactive drug suggests RCVS; subacute neurological decline weeks into checkpoint inhibitor or propylthiouracil treatment suggests vasculitis. In both, identifying and stopping the drug is the first management step.
- In RCVS, review and stop serotonergic and vasoactive drugs, including over-the-counter decongestants.
- Consider CNS vasculitis with new neurological symptoms on checkpoint inhibitors or propylthiouracil.
- Report suspected cases to the national pharmacovigilance programme (PvPI in India).
- Note teprotumumab as a new RCVS signal in thyroid eye disease.
Why it matters
Drug withdrawal is a treatment, and the timing of onset points to which drug to suspect.
Don't overread it
Disproportionality signals from spontaneous reports cannot show incidence or confirm causation.
The statistics, in plain English
A reporting odds ratio shows a drug is reported with the event more often than expected, not how often it causes it. The teprotumumab signal rests on six reports, hence the very wide interval. These are hypotheses for causality, not measured risks.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for clinical pharmacology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free