The Transition From First-Line to Second-Line Therapy in Multiple Sclerosis

  • Jan DörrEmail author
  • Friedemann Paul
Multiple Sclerosis and Related Disorders (P Villoslada, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Multiple Sclerosis and Related Disorders

Opinion statement

Sufficient control of disease activity in multiple sclerosis (MS) patients, particularly in the early phase of the disease, is crucial for the prevention of an unfavorable outcome. While currently available disease modifying drugs are generally clearly assigned as first-line or second-line treatment, no universal guidelines exist that help in the real world setting to decide when and how exactly a transition from first-line to second-line therapy should be initiated. Furthermore, the concept of first and second-line therapies is constantly evolving. In order to facilitate evidence-based decision making in this common situation, we here summarize existing data on the optimization of treatment when the first-line drug needs to be switched. Obviously, a switch of treatment starts with an exploration of the motivation to switch, which usually may be ascribed to either inadequate treatment response or tolerability, safety, or adherence issues. In the latter situation, intra class switching, e.g., from interferon (IFN) beta to glatiramer acetate (GA) or, in case of aversion against injectables, from GA/IFN beta to one of the new orals dimethylfumarate or teriflunomide can be a reasonable option. If treatment failure is the reason for a switch, existing data suggest that escalation to a more powerful drug such as natalizumab, fingolimod or even alemtuzumab is more appropriate. Of note, in some drugs, different formal approvals apply in different countries. For example, while fingolimod is approved as second-line therapy in the European Union, it can be used as first-line drug in the United States and in Switzerland. The flip side of these more powerful drugs might be a less favorable risk-benefit ratio. As long as data are not yet sufficient to allow a direct comparison of efficacy among second-line drugs, the treatment decision should be primarily based on the individual situation and risk profile of the patient.


Multiple sclerosis Treatment Escalation Disease modifying drug Treatment failure Disease activity Window of opportunity 


Compliance with Ethics Guidelines

Conflict of Interest

Jan Dörr declares the receipt of research support from Novartis and Bayer Healthcare, speaker honoraria from Novartis, Teva and Bayer Healthcare, honoraria for advisory from Teva, Genzyme, and Bayer Healthcare, and travel support from Bayer Healthcare and Novartis.

Friedemann Paul declares the receipt of speaker honoraria, travel grants, and research grants from Teva, Sanofi Aventis, Bayer Healthcare, Merck Serono, Biogen Idec; MedImmune and Novartis; travel reimbursement and research support by the Guthy Jackson Charitable Foundation; support by the German Research Foundation (DFG Exc 257), the German Ministry of Education and Research (Competence Network Multiple Sclerosis), the Artur Arnstein Foundation and the Werth Foundation of the City of Cologne. Member of the steering committee of the OCTIMS study sponsored by Novartis.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research CenterCharité-Universitätsmedizin BerlinBerlinGermany

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