Remyelinating therapies are often considered to be the holy grail of MS treatments. The ability to repair, remyelinate, and potentially reverse disability in patients with MS would be a major advance. Lessons drawn from clinical trials in other diseases in which patient selection, the timing of treatment, and the course of the disease are strongly related to the efficacy of a potential therapy could also be applied to the trial design for treatments with remyelinating potential. You could have an agent that has remyelinating potential, but its efficacy may be dependent on when it is used as it relates to MS disease course or to disease activity. There may be a remyelinating drug with great potential, but it could potentially be abandoned if it is studied in the wrong context. Thus, I think that trial design for remyelinating therapies is very important and that remyelinating treatment will be an area of transformation over the next 10 years.

Some of the success of these trials may be dependent on patient selection. We may want to select patients for clinical trials who are the most likely to respond or who have the greatest capacity for remyelination. That may require new magnetic resonance imaging tools to identify those with intact axons and, therefore, the substrate for remyelination. We also know that younger patients have a greater potential for remyelination than older individuals and that selecting a younger patient group for clinical trials to establish a signal for efficacy may be a necessary first step. If evidence of efficacy is observed, the patient population could be expanded more broadly in follow-up studies.

One of the huge success stories over the last 25 years in MS care has been the US Food and Drug Administration approval of highly active disease-modifying therapies. If such treatments were available to patients with Parkinson’s disease or Alzheimer’s disease, with definitive evidence that the medications slow disease progression, it would be heralded as an amazing advance. So, I think that we have come very far in MS clinical trials, and I think that one thing that is exciting on the clinical trials front is that we are now beginning to test different treatment strategies and to learn how to use our therapies optimally.

Two ongoing trials funded by the Patient-Centered Outcomes Research Institute are comparing different treatment approaches for MS. The DELIVER-MS study is designed to evaluate the strategy of using highly active disease-modifying therapy first line vs a treatment escalation strategy. The second trial (ie, the TREAT-MS study) is similar, randomizing participants to highly effective therapy vs treatment escalation and measuring clinical disability outcomes and biomarkers. The DELIVER-MS and the TREAT-MS studies are each considered a second-generation type of clinical trial, where they are not only an evaluation of an individual agent vs placebo or another single agent but also an evaluation of a treatment strategy to determine how we should be using the tools that we have accumulated over these last 25 years. I am excited to see the results of these trials and to have answers for neurologists that will hopefully guide more informed choices of therapy rather than a trial-and-error approach, which is often the way it works now.

Most trials are short-term drug trials, like 1 or 2 years, with a younger population. So, trying to choose a lifetime treatment based on a trial like that is like trying to choose the winner of a marathon at mile 2. You just cannot do it.

Clinical trials for MS need to include older patients because most of the MS population is an aging population. We need safety data for patients in their 50s and 60s, as well as more long-term follow-up data, which is difficult to obtain because many patients switch from one drug to another. When I look at pivotal clinical trial results, I already know that they are likely to have great results for magnetic resonance imaging and pretty good results for relapse prevention, with disability being a distant third. I sometimes tell drug reps, “Just show me your disability data.” Of course, the drug is going to work, otherwise it would not have been approved. I want to see the difference that it will make in a patient who takes this drug for 10 years. Will it prevent relapses and allow patients to walk? I do want to hear about the other outcomes, but they are less important. I focus on disability data, although they are difficult to obtain in short-term studies. I also look at trial results in terms of patient ages to determine whether there is peak efficacy in certain subgroups. Answering these questions will definitively require larger patient groups and will make the trials more costly.

Additionally, if there was some way to determine the robustness of a patient’s immune system, to have the ability to tailor treatment with either a high- or low-efficacy drug, or to determine whether the patient needs a specific type of drug, that would be a major advancement. Right now, everything is a shotgun approach based on efficacy. If we could identify individual drivers for MS and tell patients whether they have a cytokine-driven disease or a B-cell–driven disease, we could make more informed treatment decisions.