Utilizing Biomarker Panels to Effectively Gauge, Manage Multiple Sclerosis

Taylor Gonyou, DO

At the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 23-25, in San Diego, California, a group of investigators presented a real-world case series assessing Octave Bio’s multi-protein Multiple Sclerosis Disease Activity (MSDA) test. Analytically and clinically validated, this test utilizes an algorithm that contains 18 biomarkers to produce 4 disease pathway scores covering immunomodulation, neuroinflammation, myelin biology, and neuroaxonal integrity, as well as an overall disease activity (DA) score.

Led by Taylor Gonyou, DO, the case series featured 5 patients with MS with various ages, disease durations, disease-modifying therapy use, and radiographic presentations. Using the MSDA, each patient received a disease activity score, which correlated with clinical relapses, radiographic brain and/or spinal disease, and efficacy of the therapy. Participant 1, a 35-year-old Caucasian female with a disease duration of 6 years, had an MSDA score of 8, the highest of any participant, and was told to discontinue natalizumab. She originally started natalizumab in October 2021, but continued to have breakthrough disease on a subsequent brain MRI in August 2022, which revealed several new, non-enhancing lesions. After further testing showed neutralizing antibodies, she was subsequently placed on ocrelizumab (Ocrevus; Genentech).

Gonyou, an MS fellow at Michigan Institute for Neurologic Disorders, sat down at the Forum to discuss the biomarker panel in detail, including how it can change monitoring and clinician decision-making. She provided insight on the implications of these findings, potential future research, and how the MSDA could be expanded in the future.

NeurologyLive®: What are some of the advantages this tool brings?

Taylor Gonyou, DO: The MSD score is a test that utilizes 18 different blood biomarkers, it gives you 4 disease pathway scores, and an overall disease activity score. The disease activity score ranges from 1 to 10, which includes ranges of 1-4, 4.5-7, and 7.5-10. That's a low, moderate, and high risk for a potential relapse, or particularly a new gadolinium enhancing lesion.

In terms of clinical advantages, this can be helpful in many ways. It really is precision medicine for the first time in MS. It’s good in that you can find a baseline for patients—where does the patient stand from the first time when getting this test—and then follow them longitudinally over time. It's another way that you can use their subjective symptomatology and combine it with objective data, making the invisible, visible per se. I think it will be helpful for clinicians in the future, not only for pre and post treatment, but to watch these patients over time.

Are there biomarkers that hold more weight than others in the algorithm?

Being at ACTRIMS in the last few days, I've heard so much about NfL (neurofilament light) and GFAP (glial fibrilary acidic protein), but I think the most amazing part of this score is that it incorporates all 18. One alone is not as reliable as when you can combine all these different numbers together, and then get your score. All of them in uniform is what makes this score so special.

In the results, what stood out to you?

Each case was a little bit different. The one that stuck out the most to me was that we had a patient who relapsed on a high efficacy therapy, one that you wouldn't expect them to have a relapse on. We checked the disease activity score on them, it was an 8, indicating that they were high risk. We also got an MRI which had new lesions, kind of corresponding to that. That right there shows you that it can be high during a relapse.

Another interesting case that was a patient who had a relapse, then switched to a high efficacy therapy. After being on the high efficacy therapy, her score was a 1, so very low. It just shows you how much the disease correlates with the treatment that you're on.

For another patient that we had, it was kind of a baseline test. This patient was not on therapy, and her score was a 6, kind of showing she is in that moderate risk group, and that she is at risk for relapse. I'm curious to kind of follow these patients over time and see how their scores change.

Do you have thoughts on possibly expanding this type of research?

This poster includes just five patients, but I've been using this score on a lot of my patients for a while now, and I'm finding it to be extremely helpful. For our clinic, we've found it to be useful not only just following the patients over time, but potentially even guiding therapy decisions. The more people that are aware of this score, the more useful it can be for patients not only to guide treatment, but to monitor these patients over time and see how these scores evolve.

Are there complications with implementation of this approach?

Octave is already being used in MS centers across the country, and they're very involved with multiple different MS clinics. That's kind of how this whole thing started. Hopefully it just keeps expanding, but I definitely think they're already being utilized. Something that's nice for patients is that they have a generous financial assistance program in concordance with the federal government that can allow these patients to get this test and have it be accessible to everyone, which is amazing.

How is this test used in conjunction with the tools already being used in clinic?

When a patient comes to you, you can see the MRI, you can see their clinical picture, and you might have an idea of, is this patient more progressive? Or is this patient maybe going to be less progressive or more highly active disease? But I think that utilizing this score with that, and following it longitudinally, shows you that maybe I didn't think this patient was that high risk for relapse at first, but now I've watched things change and I've watched that score shoot up, which might change my mind a little bit that maybe I do need to alter therapy.

Are there aspects of the tool that we’re still trying to understand?

The score that we have now is really heavy on relapsing MS. It is great for looking at relapses from what we see clinically, and our personal experience, but the one thing it's kind of lacking is that progressive part. Essentially, the smoldering, progressive MS. Can this be used in that? For this specific test we have now, the answer is probably no, but from what I'm hearing it is in the pipeline, and probably something to come. I'm especially excited for when that comes out, and we'll be able to use that in that patient population that's currently lacking.

Transcript edited for clarity. Click here for more 2023 ACTRIMS coverage.