Long-term follow-up of multiple sclerosis studies and outcomes from early treatment of clinically isolated syndrome in the BENEFIT 11 study

  • Hans-Peter HartungEmail author
  • Jonas Graf
  • David Kremer


Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a diverse disease course involving inflammation and degeneration of neurons and axons. Multiple sclerosis results from a complex interaction of genetic and environmental factors and clinically several disease subtypes with marked variation in symptoms can be discerned. Disease-modifying therapies (DMTs) impact disease activity and outcome. Long-term follow-up studies of DMTs in MS have generally shown that the short-term effects in clinical trials are maintained for up to 21 years, e.g. in the case of interferon beta-1b. However, attainment can be a problem in these studies. On the one hand, so-called real-world studies can augment clinical trials by providing data on the long-term effectiveness and safety of DMTs but lack, on the other hand, randomization and may, in addition, also yield biased findings as a result of compliance issues. Long-term data from clinical trials in clinically isolated syndrome (CIS) patients have been limited but in the case of interferon beta-1b this aspect has been addressed over 11 years in the BENEFIT 11 trial. The results suggest that early treatment results in persistent long-term benefits including conversion to clinically definite MS (CDMS) as well as time to and risk of a first relapse. Here we primarily review the findings of the BENEFIT 11 trial in the context of long-term studies.


Long-term follow-up Multiple sclerosis Clinically isolated syndrome Early treatment Real world data BENEFIT 11 study 



We thank Eva-Maria Wicklein for her support in reviewing and commenting on the manuscript. Medical writing support, including preparation of the drafts under the guidance of the authors, was provided by Ray Ashton, Richmond Medical Communications. All named authors meet the criteria of the International Committee of Medical Journal Editors for authorship for this manuscript, take responsibility for the integrity of the work as a whole and have given final approval for the version to be published.


The publication of this article was supported by Bayer AG. The views and opinions expressed in the article are those of the authors and not necessarily those of Bayer AG. The original BENEFIT trial was sponsored by Schering AG / Bayer AG.

Conflicts of interest

Hans-Peter Hartung has received fees for consulting, serving on steering committees and data monitoring committees from Bayer Healthcare, Biogen, GeNeuro, Medimmune, Merck, Novartis, Roche, Sanofi Genzyme, Teva, with approval by the Rector of Heinrich-Heine-University. Jonas Graf has no conflicts of interest. David Kremer has received compensation for speaking for Grifols SA.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, UKD, Center for Neurology and NeuropsychiatryLVR Klinikum Heinrich-Heine-University DüsseldorfDüsseldorfGermany

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