With the availability of nearly 20 medications approved for relapsing forms of multiple sclerosis (MS), there is growing pressure to better define how to select the most appropriate treatment for a given individual, particularly at the time of diagnosis. MS disease-modifying therapies differ in efficacy in reducing risks of relapse and lesions on brain magnetic resonance imaging (MRI) at the group level. However, these data can be hard to apply to an individual person with MS, who may have no further discernable MS activity after starting a specific therapy or may have dramatic breakthrough disease. Further, it is not entirely clear how different treatment approaches relate to longer-term disability risk. Randomized clinical trials have demonstrated short-term benefits of some specific higher-efficacy therapies with respect to disability outcomes compared to another, specific moderate-efficacy therapy, but these trials have not tested treatment strategies; in particular, escalation after ongoing MS activity is not typically allowed in such protocols. In the real world, people with MS who have breakthrough disease on a moderate-efficacy therapy often change medication, switching to a different moderate-efficacy medication or escalating to a higher-efficacy therapy. Some observational data suggest early use of higher-efficacy therapies may reduce longer-term risk of disability, but these studies were not able to account for confounding by indication or other biases.
To provide an overview of the state of knowledge surrounding the effects of various treatment strategies on longer-term MS outcomes.
In this session, we will review the literature that addresses treatment strategies in early MS, particularly assessing the impacts of using a more aggressive therapy as the first treatment versus adopting an escalation approach. We will also discuss two ongoing randomized trials, TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) and Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (DELIVER-MS), which seek to systematically determine if a given treatment strategy best prevents longer-term disability and brain atrophy.
There remains a large gap in knowledge regarding how specific treatment strategies during early MS in the real world optimally prevent, delay, or reduce intermediate- to longer-term disability accrual. The infectious risks and other complications associated particularly with higher-efficacy treatments are a major concern for people with MS and their clinicians, perhaps made even more clear during the COVID-19 pandemic.
It is critical to define if applying a specific treatment strategy across the board confers long-term benefits for functioning. Ongoing pragmatic randomized clinical trials will provide key information about the relative benefits and risks of various treatment strategies.