Rationale and Design of the Traditional Versus Early Aggressive Therapy for MS (TREAT-MS) Trial

Background: Multiple sclerosis (MS) disease-modifying therapies target the relapsing phase of MS but have minimal impact once the progressive phase has begun. It is unclear if, in the relapsing phase, there is an advantage of early aggressive therapy with respect to preventing long-term disability. The risks associated with higher-efficacy treatments highlight the need to quantify their effectiveness in preventing disability.

Objectives: To describe the rationale and design of TREAT-MS trial.

Methods: TREAT-MS trial is a pragmatic, randomized controlled trial with two primary aims:1) to evaluate, jointly and independently among patients deemed at higher-risk versus lower-risk for disability accumulation, whether an “early aggressive” therapy approach, versus starting with a first-line therapy, influences intermediate-term risk of disability;2) to evaluate if, among patients deemed at lower-risk for disability who start on first-line therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a new first-line therapy have different intermediate-term risk of disability.

Results: The TREAT-MS final protocol was adjudicated by a Study Advisory Committee(includes patients;stakeholders;expert clinicians;statisticians). 900 participants are being categorized as being at lower versus higher-risk of longer-term disability and then randomized, stratified by this risk, to higher-efficacy versus first-line therapies. We will evaluate if there is an intermediate-term benefit, with respect to disability, of higher efficacy therapy and if that benefit differs based on baseline disability risk. We will also explore, in those deemed at lower-risk of long-term disability at onset, if switching to another first-line therapy versus escalation to a more aggressive medication has an impact on subsequent disability measures. Additional outcomes include patient reported outcomes and imaging obtained as standard of care.

Conclusions: There is a great unmet need to identify the most appropriate treatment strategy in MS, especially early in the disease course when it may be possible to maximize an individual’s chance for preventing long-term disability. TREAT-MS trial will address this critical gap in knowledge.