John Chen, MD, PhD, of the Mayo Clinic, talks with Ophthalmology 360 about treatment options for neuromyelitis optica spectrum disorder (NMOSD) and how timely treatment is important to avoid permanent vision damage in these patients. He also talks about a study he is part of that is currently enrolling patients. Learn more about the TIMELY-PLEX study. Contact the researchers to enroll your patients.
Question:
What are the symptoms of neuromyelitis optica spectrum disorder and what effects can this rare autoimmune condition have on patients?
John Chen, MD, PhD:
NMOSD, neuromyelitis optica spectrum disorder, the 2 main ways it presents is severe optic neuritis and severe transverse myelitis. That’s why as ophthalmologists we care about the disease is because of the optic neuritis. It can also cause other areas of inflammation in the brain, including something called area postrema syndrome, where patients actually will have unexplained hiccup, vomiting, nausea. It can cause other areas of inflammation. But again, I’d say at least the second most common feature is optic neuritis and severe vision loss.
Question:
What are the available treatment options for patients with NMOSD?
John Chen, MD, PhD:
Because the attacks are so severe and the outcomes are so poor, we actually treat the acute attacks very aggressively. We always think about optic neuritis, we think about MS. Only 3% of patients with MS optic neuritis end up at 20/200 or worse. On NMOSD, it’s about a third to 50% of patients can end up 20/200 or worse. These acute attacks, we’re going to treat them with IV corticosteroids high dose, and we’re going to do something called a plasma exchange where we essentially take the blood, use a plasma exchange machine to remove the pathologic antibody cytokines and to washout, essentially all the damaged biomarkers there to try and get recovery. That’s in the acute setting, IV steroids, plasma exchange.
Then because up to 90% of these patients are going to relapse and every attack could cause them blindness, could cause them to be wheelchair-bound, they need to be on chronic immunotherapy immunosuppression to prevent new attacks. Fortunately, we have FDA-approved medications now for this disease that can have a reduction of relapses as high as 94%. As close to a cure as could be. There’s some complement inhibitors, eculizumab, ravulizumab. There’s CD19 and 20 blockers, rituximab and inebilizumab. Then IL-6 inhibitors, satralizumab. These are all options that we’ll want to invoke in these patients of NMOSD. It’s good to pair up with a neuro-immunologist and urologist to help with this because again, if they have a relapse, it could be the next attack leaving them blind or wheelchair-bound. Even if they have recovery from that first attack, they need to be on chronic treatment.
Question:
What are the goals of treatment for these patients?
John Chen, MD, PhD:
The acute treatment, try to get as much back as possible. Then the chronic treatment is to prevent that relapse. It’s very important when you have a patient with optic neuritis to think about NMOSD because the treatments for NMOSD are completely different from multiple sclerosis. Some of the traditional older medications for MS not only didn’t work for NMOSD in terms of disease prevention, they may have even increased the relapse rate. When you have a patient with optic neuritis, I mean checking their blood for aquaporin 4 antibodies. Those are the biomarker for NMOSD. Again, when we’re checking for these biomarkers, we should also check against MOG antibodies, a biomarker for MOG antibody-associated disease called MOGAD, because again, MS, NMOSD, and MOGAD all have different prognoses and most importantly different treatments.
Question:
Are there any areas of research related to NMOSD that interest you?
John Chen, MD, PhD:
I would say probably 1. One is that for NMOSD, it’s neuromyelitis optica spectrum disorder, and we’ve got a very good biomarker for it, the antibodies against aquaporin 4. But about a third of NMOSD actually remains seronegative. That means they’re negative for aquaporin 4, they’re negative for MOG. That means there’s some other antibody that’s out there that we don’t know. Definitely a strong interest for me and at the Mayo Clinic and among many others is trying to find that next biomarker. In fact, the antibodies against MOG that I just mentioned, that was only discovered about 10 years ago, and now we found that that explained about a third of what was previously shown in NMOSD. But there’s still more antibodies to be discovered. That’s one thing.
Second, we talked about how plasma exchange is typically used for patients with NMOSD because the outcomes are so poor. The exact timing of it is still somewhat debatable. I think multiple studies, mostly retrospective, have all suggested the earlier the plasma exchange the better. But it’s hard to know that based on retrospective studies because patients early on may just get better even without the plasma exchange.
We actually have a very large multicenter clinical trial that we’ll start enrolling in the next couple months called TIMELY-PLEX. We’re going to be taking patients with severe optic neuromyelitis of any etiology. Some of these may end up being NMOSD. We’re going to randomize them to early plasma exchange and steroids right off the bat, randomized to a group who will get just IV steroids alone. If there’s no recovery at 2 weeks, then they can get the delayed rescue plasma exchange.
The clinical trial is called TIMLEY-PLEX, and we’re going to have 31 sites around the US enrolling for this clinical trial. We’ll also be enrolling severe transverse myelitis, Elias Sotirchos, MD, at Hopkins is the co-PI between myself and him. But again, we’re going to be looking for any patient with severe optic neuritis. We’re going to be looking for those patients to enroll them within 8 days to figure out if early PLEX truly does lead to better outcomes. Definitely look out for that posting and we’d welcome any patients that you might see.
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