Risk of serious liver damage with MS drug daclizumab

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended further restrictions to the use of the multiple sclerosis (MS) treatment daclizumab (Zinbryta), following clinical trial reports of serious liver damage.

Daclizumab is a humanised monoclonal antibody that modulates interleukin (IL)-2 signalling by binding to CD25 (the alpha subunit of the high-affinity IL-2 receptor) thus inhibiting activated T cell responses. It is licensed for the treatment of relapsing forms of MS in patients with highly active disease despite a full and adequate course of treatment with at least one disease-modifying therapy, or in those with rapidly evolving severe relapsing MS who are unsuitable for treatment with other disease-modifying therapies. It is given as a 150mg subcutaneous injection in a prefilled syringe or pen once a month.

PRAC carried out of a review of daclizumab’s effects on the liver, and found that potentially fatal immune-mediated liver injury can occur both during treatment and for up to six months after stopping the drug. Serious liver reactions occurred in 1.7% of patients in clinical trials. Because of this risk, PRAC recommends that daclizumab should only be prescribed for relapsing forms of MS in patients who have had an inadequate response to at least two disease-modifying therapies and who cannot be treated with other disease-modifying therapy.

In those who are given daclizumab therapy, liver function tests (serum transaminases (ALT and AST) and bilirubin) should be monitored at least once a month as closely as possible before each treatment, and then for up to six months after treatment has been stopped. Treatment should be stopped if a patient has liver enzymes over three times the normal limit, and patients with signs and symptoms of liver damage, or who test positive for hepatitis B or C infection, should be referred to a specialist.

PRAC adds that daclizumab must not be used in patients with pre-existing liver disease, or started in new patients with over two times the normal limit of liver enzymes. It also recommends that healthcare professionals should use an acknowledgement form to confirm that they have discussed the risk of liver damage with their patient, and that the patient understands the importance of monitoring for liver damage.

The PRAC review has now been forwarded to the CHMP, which will form a final opinion on the recommendations.

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