Advice for healthcare professionals:
- Following the initiation of an urgent safety review, the European Medicines Agency (EMA) recommends that:
- 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 (eg, 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 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.
- patients should talk to their doctor if they have any questions about daclizumab
- EMA’s recommendation to suspend Zinbryta and recall the product is being sent to the European Commission for a legally binding decision
Cases of serious inflammatory brain disorders
An urgent EU-wide review of the safety of daclizumab has started. As of 7 March 2018, the EMA had received reports of 12 patients worldwide who developed serious inflammatory brain disorders, including encephalitis and meningoencephalitis, in association with daclizumab. There have been some fatal cases and most other patients remain critically unwell.
Risk factors have not been identified and most patients did not respond to treatment including corticosteroids and/or plasmapheresis. Available evidence also indicates that daclizumab could be linked to other immune-mediated disorders, such as blood dyscrasias, thyroiditis, or glomerulonephritis.
Worldwide, more than 8,000 patients have been treated with daclizumab in clinical trials and post-marketing. There have been no reported cases of serious inflammatory brain disorders in the UK, in which use of daclizumab has been very low (less than 100 patients) and mainly been in clinical trials. The MHRA have sent letters to the Association of British Neurologists and to patient groups to inform them of the recommendations.
The company has also informed EMA of its decision to stop ongoing clinical studies with Zinbryta in the EU. Patients in clinical studies who have any questions should contact the doctor treating them in their study.
Daclizumab (Zinbryta▼) 150 mg solution for injection was authorised in the EU in July 2016 for the treatment of adults with relapsing forms of multiple sclerosis. Following a 2017 review of the medicine’s effects on the liver, the use of the medicine was restricted to patients who have tried at least two other disease-modifying treatments and cannot be treated with any other multiple sclerosis treatments. The 2017 review also recommended that liver function should be closely monitored before each daclizumab dose (or more frequently if clinically indicated) and for up to 6 months after the last dose, see Drug Safety Update, January 2018.
Call for reporting
Healthcare professionals should continue to report any suspected adverse drug reactions to daclizumab to the Yellow Card Scheme.
Announcement from the European Medicines Agency. 7 March 2018.
Article citation: Drug Safety Update volume 11 issue 8; March 2018: 1.