Safety Considerations for Therapies in NMOSD

EP: 1.Overview of Neuromyelitis Optica Spectrum Disorder (NMOSD)

EP: 2.Differential Diagnosis and Types of NMOSD

EP: 3.Pathophysiology of NMOSD

EP: 4.Progression of NMOSD Over Time

EP: 5.Initiating Treatment and Goals of Therapy for NMOSD

EP: 6.Treatment Selection in NMOSD

EP: 7.Recent Approvals for NMOSD Treatment

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EP: 8.Safety Considerations for Therapies in NMOSD

EP: 9.Effects of Polymorphism in the Use of Anti-CD19 and Anti-CD20 B-cell Therapy in NMOSD

EP: 10.Use of FDA Approved Disease-Modifying Therapies vs Other Treatments in NMOSD

EP: 11.Approaches to NMOSD Treatment in Clinical Practice

EP: 12.The Unmet Needs in NMOSD

EP: 13.Practice Pearls for Management of NMOSD

Brian Weinshenker, MD: Dr Nelson, can you tell us a bit about safety considerations for these drugs for neuromyelitis optica spectrum disorder (NMOSD) and what are the key safety issues that have come up for each of them?

Flavia Nelson, MD: Of course. Well, as we had talked about, these are relatively new therapies approved in the past couple of years. Most of us in the field are used to using anti-B-cell therapy. So, we know very well that those anti-B-cell therapies have a lot of infusion reactions, which can be controlled with premedication. These newer therapies also have many side effects, including infusion reactions as well as injection-site reactions.

There can be multiple complications such as fever, nausea, headache, and infections. I think the most important thing for all of them is the degree of immunosuppression that can be caused, which can predispose patients to infections such as COVID-19 among others. I have to say that in my limited experience with all of them, we’ve seen some very serious side effects, especially with eculizumab, in terms of skin reaction or autoimmune lupus that was not officially described. So aside from the well-known side effects that we know about, we can also see unexpected reactions depending on the case.

Brian Weinshenker, MD: Dr Nelson, can we talk about a few of these individually? For eculizumab, there’s one infection that there’s a specific warning about. Could you tell us about that?

Flavia Nelson, MD: Yes. That is correct. It’s recommended to give the meningococcal vaccine prior to this treatment because of the risk of meningococcal infection. You are correct.

Brian Weinshenker, MD: OK.

Flavia Nelson, MD: Very important.

Brian Weinshenker, MD: There are 2 different meningococcal vaccines. There’s the polyvalent, which covers most of the meningococcal subtypes. Now there’s 0 type B vaccination as well, and both are important to administer.

Flavia Nelson, MD: Correct.

Aaron Miller, MD, FAAN: I think it’s maybe worth mentioning that in the eculizumab trial in NMO [neuromyelitis optica], there were no cases of meningococcal infection. Of course, everybody was vaccinated. There is a subsequent generation of complement inhibitors known as rovelizumab, which has the advantage of less frequent administration than eculizumab and has had a trial in NMOSD. It’s not yet FDA-approved for this purpose. It is on the market already for myasthenia gravis. In that trial, despite the immunizations, there were 2 cases of meningococcal infection. It’s not something to take trivially.

Brian Weinshenker, MD: In the phase 2 clinical trial of eculizumab that was conducted before the phase 3, there was a case where 1 out of 14 patients did develop meningococcus and recovered well. You’re absolutely right that this should be a significant concern. Bob, with inebilizumab, what about the risk of infection with that drug? It is a B-cell depleter?

Robert Shin, MD, FAAN: Sure. One comment I would make is maybe it isn’t surprising. Of course, we have to watch out for meningococcus with an anti-complement strategy since the purpose of the complement is to help fight off/encapsulate organisms like meningococcus. That’s not a surprise. I would say when we’re talking about an anti-CD19 agent, a B-cell therapy, I think of it similarly to how I think of anti-CD20 agents. I need to screen my patients to make sure they don’t have active infections like hepatitis B, for example. Usually, we’ll do immunoglobulin [IgG] screening as well to make sure there aren’t preexisting deficiencies in IgG levels as well as metabolic labs. Fortunately, and I would say for all the treatments on the whole, infection rates have been quite low. You’re right, when we’re going to use a B-cell therapy, we’re certainly going to be vigilant.

Brian Weinshenker, MD: The rates of hypogammaglobulinemia so far are quite low. This is something that develops over years, and it will need to be monitored.

Aaron, I think you answered this, but I’m going to ask you again. We don’t have head-to-head comparisons. Do you think it’s possible to draw conclusions about the relative effectiveness of these drugs?

Aaron Miller, MD, FAAN: I really don’t think on the currently available data that it would be fair to conclude that one of these drugs is more efficacious than the other. It is certainly a possibility it would take a head-to-head trial, which I think is highly unlikely that we’re going to see. So, at the moment, I think in my personal practice, if I’m going to choose among these agents, I’m really going to listen and engage with the patient about his or her life lifestyle. And usually, it’s a her, of course, because this is 9 times more common in women than men. I’m going to listen to what are her concerns.

Obviously, you’ve already made the point that getting every 2-week intravenous infusions, especially for a person who might already have a significant neurological disability, could be very challenging. There are people, as we know from our experience going back years in MS, who are needle phobic and, in those circumstances, they never want to give themselves a shot. So satralizumab might not be the right thing for that person. A person who’s a far distance from an infusion center, on the other hand, might shy away from inebilizumab and may prefer the subcutaneous injection.

Brian Weinshenker, MD: So, a lot of practical considerations of lifestyle and convenience.

Transcript edited for clarity