Rituximab vs Fingolimod in JCV+ Individuals

Research Summary: Rituximab versus fingolimod after natalizumab in multiple sclerosis patients

The background

Whilst natalizumab has emerged as a potent treatment for multiple sclerosis (MS), it is also associated with the risk of developing a serious and fatal brain condition known as progressive multifocal leukoencephalopathy (PML).  As we have discussed previously, PML is caused by the JC virus.  For this reason, people taking natalizumab are routinely monitored for the presence of antibodies against this virus.  The presence of these antibodies is used as a marker of infection with the virus.  People who become positive for the JC virus whilst taking natalizumab cease this treatment and then have to choose whether to switch to an alternative treatment or to stop therapies altogether.

The study

This study, conducted by researchers at the Karolinska Institute, the University of Gothenburg and Umea University, aimed to assess this situation in people with MS in Sweden.  Specifically, they investigated people who stopped the use of natalizumab due to becoming positive for the JC virus and compared their outcomes depending on whether they switched to fingolimod or rituximab.  The study included 256 eligible participants, 55% of which had shifted to fingolimod.  The outcomes were measured by evidence of disease activity on MRI, the occurrence of a clinical relapse and any adverse clinical events experienced.

The findings

The results showed that, in general, people who switched to rituximab experienced significantly less adverse events, less clinical relapses and fewer lesions on MRI.  It was also shown that people with MS who switched to rituximab stayed with this treatment option for longer than those who transferred to fingolimod, which was found to be due to the lack of effectiveness of fingolimod in that group.

The outcomes

This study has found that rituximab seems to be a much more effective therapy for people with MS that are discontinuing their use of natalizumab due to becoming JC virus positive.  Currently, rituximab is routinely used for the treatment of rheumatoid arthritis and B-cell lymphoma.  However,  despite the fact that it sometimes used as an off-label treatment for MS, only one Phase II clinical trial has been completed in people with RRMS.  This study provides strong support for further randomised clinical trials to be conducted to confirm the effectiveness of rituximab as a treatment for MS, especially as an alternative for natalizumab.

The abstract of this study can be found here.