The following statement was released last Friday on the EMA’s website. It is reassuring that the EMA has decided not to withdraw daclizumab product from the market. I still think there will be a group of pwMS who will benefit from the therapy. For example, patients at (1) high-risk of PML transitioning from natalizumab, those with (2) PML post-natalizumab and (3) patients with high-disease activity who don’t want an irreversible therapy nor therapies that cause continuous immunosuppression. The elephant in the room is that in both fatal cases, those who died of liver failure on daclizumab also received concomitant tizanidine. Could tizanidine, or other hepatotoxic drugs, when used in combination with daclizumab, be the problem? I suspect the use of daclizumab will now be so low we won’t be able to answer this question with post-marketing surveillance.
Zinbryta to be used only in a restricted patient group, with strict liver monitoring
PRAC is recommending further restrictions on the use of the multiple sclerosis medicine Zinbryta (daclizumab) following a review of the medicine’s effects on the liver.
The review found that unpredictable and potentially fatal immune-mediated liver injury can occur during treatment with Zinbryta and for up to 6 months after stopping treatment. In clinical trials, 1.7% of patients receiving Zinbryta had a serious liver reaction.
In order to reduce the risks, doctors should now only prescribe Zinbryta for relapsing forms of multiple sclerosis in patients who have had an inadequate response to at least two disease-modifying therapies (DMTs) and cannot be treated with other DMTs.
In addition, doctors should monitor patients’ liver function (ALT, AST and bilirubin) at least once a month as closely as possible before each treatment and continue monitoring them for up to 6 months after treatments have stopped.
If the patient does not comply with monitoring requirements or the response to treatment is inadequate, doctors should consider stopping treatment.
It is recommended that the doctor should stop treatment if a patient has liver enzyme levels over 3 times the normal limit and refer any patients with signs and symptoms of liver damage to a liver specialist.
Patients who test positive for hepatitis B or C infection should also be referred to a specialist.
Zinbryta must not be used in patients with pre-existing liver disease and should not be started in new patients with over 2 times the normal limit of liver enzymes. It is recommended that doctors do not use Zinbryta in patients with other autoimmune conditions.
The PRAC is also recommending that in addition to the current educational material, patients and healthcare professionals in the EU should be given an acknowledgement form. The form will be used to confirm that doctors have discussed the risk with their patients and that the patients understand the importance of monitoring and checking for signs of liver damage.
These recommendations, which strengthen provisional measures introduced in July 2017, will now be sent to EMA’s Committee for Medicinal Products for Human Use (CHMP), which will adopt the Agency’s final opinion.