Multiple sclerosis (MS) is a leading cause of disability among young adults in North America and Europe and affects over 2.5 million people worldwide. When deciding on a disease-modifying treatment (DMT), persons with relapsing-remitting multiple sclerosis (PwRRMS) and neurologists are currently faced with the dilemma of adopting one of two treatment approaches: an escalation approach, starting a drug that is considered safe but with a modest likelihood to control the MS activity (attacks and new lesions), and escalating to more potent therapies in the face of continued disease activity; or an early highly effective treatment (EHT) approach, which, in contrast, involves giving a high-efficacy drug, with the rare potential for significant adverse effects, as the first-line treatment. Despite significant interest from both patients and care providers on this topic, there is currently no evidence comparing these two approaches in a head-to-head trial.
This study is a multicenter randomized clinical trial. Subjects will be randomized in a 1:1 ratio to a specific approach for the first-line therapy, EHT, or escalation. The study population will be PwRRMS who have never been on a DMT recruited from MS treatment centers in the United States and the United Kingdom. Minimal entry criteria were selected to ensure the study will include patients who are representative of the general population of PwRRMS.
The aims for this study are to determine if either DMT approach (EHT or escalation) better slows brain volume loss, is safer, is more effective, or is better tolerated by PwRRMS. The study will measure how well the participants are functioning in several areas, including cognition, arm and leg function, and eyesight. We will ask participants’ perspective of their MS symptoms, quality of life measures for neurological disease, and satisfaction regarding their DMT. We will record the treatment-emergent adverse effects, as treatment choices in MS are influenced by not only the potential benefits of treatment, but also—importantly—the perceived risks.
The results of the study will provide a framework for overall treatment choices. In clinical encounters neurologists commonly discuss with patients the lack of comparative data between these two approaches. The data produced will directly help PwRRMS weigh the balance between the potential benefits and risks of DMT by providing the benefits and risks of these two approaches. The results will also help insurance payers and government agencies make more informed decisions on medication coverage, with the overall cost of long-term disability being a driving factor. The study results will help guide overall treatment philosophy and will be applicable to a wide range of both existing and new therapies, meeting a significant unmet need in patient decision making and aiding the decision for medication approval by third parties. Thus, this project has the potential to affect a large number of PwRRMS.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.