Priorities in NMO: Biomarkers, Therapy Discontinuation, and More With Marcelo Matiello, MD

Marcelo Matiello, MD

Sometimes considered a mimic of multiple sclerosis, advancements in blood biomarkers have drastically improved the diagnosis and management of neuromyelitis optica spectrum disorder (NMOSD). With 3 currently approved therapies, patients with this inflammatory disorder now have several good treatment options, but there are still many questions that need to be answered about disease management over the long-term.

In an interview with NeurologyLive, Marcelo Matiello, MD, assistant professor of neurology at Harvard Medical School, director, neurology inpatient services, and associate director, Neuromyelitis Optica Clinic and Research Unit, spoke about some of the ongoing needs in the space that he detailed during his presentation at the 2021 CMSC Annual Meeting, October 25-28, 2021 in Orlando, Florida.

What about neuromyelitis optica spectrum disorder do we not yet understand and where is more research needed?

Marcelo Matiello, MD: There is a lot known; we have excellent clinical criteria, we have excellent blood biomarkers like aquaporin 4 IgG and MOG IgG, and we have 3 approved medications through phase 3 clinical trials and the knowledge of how helpful they are to prevent attacks. I think that areas that we still need to study are quite numerous actually. One is about how much larger the spectrum of the disease may be. So overlap situations; patients with lupus and NMO or patients with the MOG antibody, but they may have lesions that look like MS, or situations in which patients have phenotype of presentation like NMO but they are new negative for both antibodies. So that's the diagnosis, but in terms of treatment, we have approved medications for the the maintenance, for prevention, but we don't really have clinical trial information for the acute attack. And that's similar in MS. There is a trial for optic neuritis, but not a proven strategy. So it's a lot of looking into series and seeing how much plasmapheresis is helpful. There are now special situations for what to do with very aggressive presentations; What to do when patients fail medication A, B or C; which of the 3 approved medications fits a patient's profile more than others? And in those special situations, such as what to do around COVID vaccinations, what to do in women of childbearing age that want to do family planning now that we have so many options, and finally, what to do in terms of when to stop medication. So as you see, there's a lot of different areas where this is still need for more information.

In terms of need around improving diagnosis, are there any biomarkers currently being studied outside of the antibodies that are showing promise in terms of diagnosis or disease progression?

The 2 antibodies, aquaporin 4 and MOG are so sensitive and specific, so everything else may help in situations when they are not positive. But folks have looked into OCTs, the central vein sign in NMO and MOG, and they've looked into how the optic nerve lesion and brain lesions and spine lesions differentiate among those conditions. It's quite different than MS where a strong biomarker such as those antibodies is not present. So you use lots of clinical components in your evaluation plus imaging events and so on to come up with good surrogate markers or good clinical markers of how patients are doing.

In relation to biomarkers for monitoring disease status, is there a point in NMO where we would consider stopping treatment?

Many of the patients say, yes, I'm committing to this, but for how much time? In my own experience, a lot of these patients, when we say, well, it has been 3 years, they say doctor, don't stop me on this medication. Life is good, let's keep it keep going. Nonetheless, there are data, especially from Asian countries, where patients stopped treatment after a 2- or 3-year period of stability, and a large number of those patients did relapse. We know that in people with NMO or MOG disease, even if they relapse while on treatment, the relapses are much less severe. So without treatment, we would be facing a lot of risk. So, unless we find a way to really manage the disease through a different mechanism of changing the immune system, I think it's very important to continue long term. We will monitor for potential toxicity or side effects, but if that's well managed, we should keep going with the therapy.