Disease activity return after natalizumab cessation in multiple sclerosis

ABSTRACT

Natalizumab (NAT) was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis. Its considerable and sustained efficacy has been demonstrated in two phase III studies. However, there are several reasons why its use is limited in clinical practice. The main argument for stopping use of the drug is the risk of the rare but serious progressive multifocal leukencephalopathy. Other reasons are neutralizing antibodies and pregnancy. There is compelling evidence from some clinical trials and many case series that disease activity returns upon suspension or cessation of NAT. Several therapeutic strategies that have been tested to prevent or reduce the recurrence of disease activity will be reviewed in this article. Considering these data, it is evident that the decision to stop NAT treatment has different implications and consequences. A subsequent therapy after cessation of NAT is needed to reduce the risk of disease recurrence.

KEYWORDS:

• Natalizumab
• relapsing-remitting multiple sclerosis
• rebound of disease activity
• immunomodulatory therapy
• neuro-immunology

Declaration of interest

T. Derfuss is on scientific advisory boards for Biogen Idec, Novartis Pharma, Genzyme, Merck Serono, Bayer Schering, Octapharma, GeNeuro, Roche; received travel funding and speaker honoraria from Bayer Schering, Biogen Idec, Merck Serono, Novartis Pharma, Genzyme; is on the editorial board of Plos One; is a member of steering committees by Mitsubishi Pharma, Novartis Pharma, and GeNeuro; is on the executive board of ECTRIMS and received research support from Novartis Pharma, Merck Serono, Biogen Idec, Swiss National Foundation, European Union, Swiss MS Society. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.