Use of FDA Approved Disease-Modifying Therapies vs Other Treatments in NMOSD


Neurology experts expand on advantages and disadvantages of using FDA-approved treatment compared with other therapy options for neuromyelitis optica spectrum disorder.

Brian Weinshenker, MD: I think this is an important discussion because I think doctors in the community, in particular, might be inclined if a patient has been treated with rituximab, and not doing well for some reason, would they shy away from inebilizumab and maybe favor satralizumab or eculizumab as the next option? This information may dispel that decision. That may not be a valid assumption.

It gets to another point which we didn’t talk about much with the selection of drugs. That is, we work in the U.S.A. where our treatment decisions are often influenced by the insurance payors. I think Flavia mentioned that briefly. I don’t think we have enough experience yet to know how much impact the payors are going to have on our choice of these drugs or our choice of these FDA-approved drugs over the older non-approved drugs.

Flavia Nelson, MD: I want to add that most of us physicians, as you said, have prescribed rituximab and most patients do well on rituximab. The question is, how do we choose these drugs? And I would like to hear what you would recommend. If patients are doing well and we’re in most cases going to choose this treatment, which is one of the fine therapies for NMO [neuromyelitis optica] based on failure as opposed to a new treatment, which is the case as well. We are now using these treatments for newly diagnosed cases.

There are a lot of cases that are already on rituximab and doing well. We’re only going to go to these next-level drugs if they fail. How do we help community neurologists and other MS [multiple sclerosis] experts decide which one to go with? What do you think?

Brian Weinshenker, MD: It’s an excellent question that I think we have to come back to because unfortunately we really don’t have data as far as which drug is superior. Often, it comes down to cost and convenience issues. There’s at least some theoretical reason to think that inebilizumab may be superior to rituximab but we don’t really have great evidence to support that. There was some data on patients who were in the inebilizumab trial who had previously been on rituximab and when they looked at the approximately 7 patients that that applied to, they were all free of the tax on inebilizumab. The assumption that they failed one B-cell depleter means that they weren’t going to do well and that doesn’t seem to be born out.

In general, I think we tend to want to use FDA-approved agents and really the new drugs are the only ones that are FDA-approved. I think similar to probably everybody on the panel, with rituximab, even though we had difficulty getting it approved by the patient’s insurance, sometimes, we’ll hear now that until a patient has failed rituximab, they can’t be considered for one of the newer agents. I don’t know if any of you have experienced that.

Robert Shin, MD, FAAN: I have experienced battles in both directions that you’ve mentioned. In the past, sometimes I would have to justify the use of rituximab off-label because insurance companies would say that’s not approved for NMO spectrum disorder. I will be honest in saying the modern era, I’ve been challenged to use an FDA-approved therapy because the formulary may have asked that the patient steps through off-label rituximab. In a way, we’ve had to fight that battle on both ends.

I would maybe add one thing to what Dr Nelson said, at least in my opinion. The last piece we were discussing, the possibility that there are some individuals out there who may not respond to rituximab as well in an optimal way. But I don’t know who they are and that does concern me. We’ve already discussed how NMO spectrum disorder relapses. Even 1 relapse can be devastating. In my mind, I’ve thought even at the beginning, if I have the option, I have tried to rely on FDA-approved agents with clinical trial data that has demonstrated high efficacy in some sense so that I can feel that I’ve done the most that I can do to prevent that possibly devastating relapse.

Brian Weinshenker, MD: I think I should be clear that the data about the valine, phenylalanine polymorphism, and FcR [fragment crystallizable receptor] gamma R3a is not such that there’s no efficacy in those who are homozygote for phenylalanine. It’s just that they may have somewhat reduced and detectable differences. I think the significance remains to be seen.

Aaron Miller, MD, FAAN: I think that we know that NMOSD [neuromyelitis optica spectrum disorder] is such a potentially devastating illness that any attack may leave a patient with a really devastating neurological disability. Even though we have insufficient evidence to prove that these newer FDA-approved agents are more effective even than rituximab. I think we probably owe it to our patients to go to battle for them and try upfront with a newly diagnosed patient to get them on one of the FDA-approved agents. I think we can make substantial arguments. I’m not sure we’ll always be successful. I think it’s worth engaging. I’m not so sure we should be switching a patient, who’s been for years on rituximab and doing well, necessarily to one of the newer agents.

Flavia Nelson, MD: I agree with you, Aaron. We also have to remember that in order to get these medications approved by the insurance companies the patient needs to be antibody positive. That’s not always going to be the case with every patient. In the case of patients that we know have NMOSD and are antibody negative, we are somewhat limited in what choices we have.

Transcript edited for clarity

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