Preservation of neuronal function as measured by clinical and MRI endpoints in relapsing-remitting multiple sclerosis: how effective are current treatment strategies?

ABSTRACT

Introduction: Approved medications for relapsing-remitting multiple sclerosis have shown to be effective in terms of their anti-inflammatory potential. However, it is also crucial to evaluate what long-term effects a patient can expect from current MS drugs in terms of preventing neurodegeneration. Here we aim to provide an overview of the current treatment strategies in MS with a specific focus on potential neuroprotective effects.

Areas covered: Randomized, double-blind and placebo or referral-drug controlled phase 2a/b and phase 3 trials were examined; non-blinded phase 4 studies (extension studies) were included to provide long-term data, if not otherwise available. Endpoints considered were expanded disability status scale, various neuropsychological tests, percent brain volume change and T1-hypointense lesions as well as multiple sclerosis functional composite, confirmed disease progression, and no evidence of disease activity.

Expert commentary: Overall, neuroprotective functions of classical MS therapeutics are not sufficiently investigated, but available data show limited effects. Thus, further research and development in neuroprotection are warranted. When counselling patients, potential long-term beneficial effects should be presented more conservatively.

KEYWORDS:

• Multiple sclerosis
• neurodegeneration
• neuroprotection
• NEDA
• progression
• treatment
• long-term outcome
• dimethyl fumarate (DMF)
• fingolimod
• teriflunomide

Declaration of interest

F Zipp has received: research grants from Teva Pharmaceuticals, Merck-Serono, Novartis, and Bayer; consultation funds and travel compensation from Teva, Merck-Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis, and Octapharma. Critical review and revision, language editing, and proof reading was carried out by Darragh O’Neill and Cheryl Ernest. 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.

Supplementary material

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Additional information

Funding

Underlying original work was supported by the German Research Council (CRC-TR 128 to FZ) and by the German Competence Network Multiple Sclerosis (KKNMS) which is funded by the German Federal Ministry of Education and Research.