Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod ToFingo-SuccessorReport as inadecuate




Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod ToFingo-Successor - Download this document for free, or read online. Document in PDF available to download.

BMC Neurology

, 15:96

First Online: 23 June 2015Received: 07 May 2015Accepted: 12 June 2015

Abstract

BackgroundIn light of the increased risk of progressive multifocal encephalopathy PML development under long-term treatment with the monoclonal antibody natalizumab which is approved for treatment of active relapsing remitting multiple sclerosis RRMS, there is a clear need for alternative treatment options with comparable efficacy and reduced PML risk. One such option is fingolimod, a functional sphingosin-1-receptor antagonist that has been approved as first oral drug for treatment of active RRMS. However, the optimal switching design in terms of prevention of disease reoccurrence is still unknown. Moreover, potential additive effects of both drugs on immune functions, especially with regard to migration, have not yet been evaluated.

Methods-designThis is an exploratory, open-label, monocentric, investigator-initiated clinical trial. Fifteen RRMS patients under stable treatment with natalizumab will receive one last natalizumab infusion followed by a wash-out period of 8 weeks before fingolimod treatment initiation for a period of 24 weeks. Disease activity under natalizumab and during switching will be closely monitored by assessment of relapse rate and disease severity as well as high-frequent high-resolution magnetic resonance imaging including quantitative diffusion tensor imaging. Immunological assays include longitudinal assessment of adhesion molecule expression, functional evaluation of the migratory capacity of immune cells in an in-vitro model of the blood–brain-barrier, and the quality of cellular antiviral immune responses.

DiscussionOur trial represents the first detailed and longitudinal functional analysis of key immunological parameters in the process of switching from natalizumab and fingolimod, especially with regard to potential additive effects of both drugs on trafficking and immune surveillance. Moreover, our study will generate valuable information about even subtle disease exacerbations as consequence of natalizumab cessation, which will help to understand whether a switching protocol containing a wash-out period of 8 weeks before fingolimod treatment is appropriate in terms of disease stability.

KeywordsMultiple sclerosis Natalizumab Fingolimod PML Switching  Download fulltext PDF



Author: Luisa Klotz - Berit Grützke - Maria Eveslage - Michael Deppe - Catharina C. Gross - Lucienne Kirstein - Anita Posevitz-Fe

Source: https://link.springer.com/



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