It has been reported this week that daclizumab (marketed as Zinbryta) has been added to the Pharmaceutical Benefits Scheme (PBS) in Australia.  Considering this, we thought it appropriate to provide some more information about this treatment option for relapsing-remitting multiple sclerosis (RRMS).

How does it work?

Daclizumab is another multiple sclerosis therapy that is designed as a monoclonal antibody.  You can review our article on what this means here.  Daclizumab has been developed to bind to a specific molecule in the immune system (CD25), to prevent it from working.

It has been shown that in multiple sclerosis, daclizumab works by inhibiting the activation of T-cells (cells that are known to cause damage to myelin).  Further studies have shown that daclizumab can also have positive effects in MS by increasing a specific cell type (CD56 NK cells) that can kill and remove activated T cells, as well as in altering the innate (non-specific) part of the immune system in a beneficial way.

What have trial results shown?

There have been a number of studies that have looked at the benefits of daclizumab in people with relapsing-remitting multiple sclerosis (RRMS).  However, the phase IIa (CHOICE), phase IIb (SELECT) and phase III (DECIDE) trials are the key studies of interest.  The results from these are as follows:

Phase IIa (CHOICE):  230 people with RRMS taking interferon-beta were split into groups and either received an add-on therapy of high-dose daclizumab, low-dose daclizumab or placebo.  After 24 weeks it was shown that the high-dose group had a significantly lower (61% less) number of new lesions compared to the placebo group.  This was achieved without a significant difference in the total numbers of T and B cells present.  No differences were seen for relapse rate, change in EDSS or number and volume of lesions.

Phase IIb (SELECT):  This was a randomised, double-blind, placebo controlled study involving 621 people aged between 18-55 with RRMS.  The trial went for one year and people received either high-dose daclizumab, low-dose daclizumab or placebo.  In this study, no other treatments were being used.  It was shown that treatment with daclizumab significantly decreased the relapse rate and led to a significantly higher number of people being relapse free across the trial period compared to those receiving the placebo.

Phase III (DECIDE):  This study involved 1841 people with RRMS and was designed to compare the effectiveness of daclizumab to interferon beta-1a.  The trial went for a period of 2-3 years.  It was shown that daclizumab significantly lowered the relapse rate and number of new or enlarged lesions compared to interferon beta-1a.  However, no significant change was observed across the course of the study for disability progression.

What are the side-effects?

Whilst the overall number of health risks or adverse events seen in the trials were similar for daclizumab compared to placebo or interferon beta-1a, there are some notable side-effects of the treatment.  In particular, treatment with daclizumab has been associated with an increased risk of liver injury, which in some cases can be quite serious.  It has been recommended that anyone considering taking daclizumab has their liver function tested prior to starting on the treatment and then monitored regularly once it is being used.

As well as liver injury, daclizumab was linked to a number of skin conditions (e.g rash, dermatitis, eczema) and an increased risk of serious infection.  There was also a suggestion that it may increase the risk of other autoimmune conditions.

Conclusion

Daclizumab represents another option for the treatment of RRMS.  It has been found to be a more effective therapy choice than the first-line option, interferon beta-1a, in decreasing relapses and lesions.  Although it did not improve disability progression, it should be noted that only alemtuzumab and ocrelizumab have been able to significantly decrease progression compared to interferon beta.

Considering the significant safety risks that have been identified, experts have suggested that daclizumab will be best suited to those who meet strict guidelines, have a highly active form of MS and who fail baseline therapy.

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