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

Jan Dörr, Friedemann Paul

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.