For a variety of reasons, patients with relapsing-remitting MS (RRMS) together with their neurologist can decide on starting treatment with a low or moderate-efficacy therapy. Explained why one might consider such an escalation approach, what a timely switch is, and how to execute timely escalation.


Many patients with RRMS choose to start with a disease-modifying therapy that has low or moderate efficacy, to then escalate this therapy when necessary, as opposed to starting early, intensive therapy. According to Dr. Dalia Rotstein (University of Toronto, Canada), an escalation approach can be considered because of favorable prognostic factors, long-term safety concerns, patient preferences (in terms of safety and route of administration), access, or associated cost. She emphasized that treatment response should consequently be assessed early. “MS is a highly heterogeneous disease which is largely unpredictable, especially early on. So the first 1 or 2 years of therapy can provide valuable information to determine what treatment intensity is required in the long term.” In these first 2 years, the patient should be closely monitored for relapses, MRI activity, and disability progression, while also considering levels of neurofilament light (NfL).

No randomized-controlled trials consist to guide treatment switches. When considering a switch, the neurologist should take the time to treatment effect (varying from 3– 6 months) into account, and then obtain a re-baseline MRI. In the guidelines, 1 or more relapses are usually seen as a cause for concern, as well as a Confirmed Expanded Disability Status Scale (EDSS)-progression of at least 1 point. More controversy exists regarding MRI, but anywhere between 1– 3 T2 lesions should be a reason to consider a switch.

To avoid delays in escalating therapy, vaccination in advance is important. According to Dr. Rotstein, the washout period should be minimized. In recent studies, prolonged washout periods have been associated with an elevated risk of new disease activity, particularly after terminating fingolimod treatment. She concluded that early aggressive therapy (the “hit-hard-and-early” concept) may gain popularity, but the escalation approach continues to be a viable paradigm, in view of varying disease severity, medication safety, and patient preferences.

  1. Rotstein DL. How to make a timely switch to high efficacy DMT. Abstract O006, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.

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