Twelve cases of serious inflammatory brain disorders, including encephalitis and meningoencephalitis, have been reported worldwide in patients using daclizumab for MS.
The EMA has made the following recommendations following the initiation of an urgent EU-wide safety review:
- Patients should not be started on daclizumab.
- Doctors should contact all patients receiving daclizumab as soon as possible and stop their treatment. Alternative therapy should be considered in line with national recommendations such as NICE guidance.
- Doctors should monitor all patients stopping daclizumab for adverse reactions and check their liver function tests at least monthly and more frequently if clinically indicated for up to 6 months after the last dose.
- Doctors should advise patients to seek urgent medical attention if they develop a severe headache or any symptoms of liver injury such as prolonged fever, abdominal pain, jaundice, dark urine, or unexplained nausea or vomiting; serious immune-mediated hepatic injury can occur up to 6 months after the final dose.
Risk factors for inflammatory brain disorders in patients receiving daclizumab have not been identified and most patients did not respond to treatment including corticosteroids and plasmapheresis. Other evidence indicates that daclizumab could also be linked to other immune-mediated disorders, such as blood dyscrasias, thyroiditis or glomerulonephritis.
Daclizumab is a humanised monoclonal antibody that binds to CD25 and modulates IL-2 signalling, with effects on T-cells and natural killer cells. It was first authorised in the EU in 2016 for the treatment of adults with relapsing MS. Following a 2017 review of the drug's effect on the liver, use was restricted to patients who had responded inadequately to at least two disease-modifying therapies and could not receive other MS treatments.