Shaida Khan, DO, associate professor of neurology at UT Southwestern Medical Center, reflected on a recent NeurologyLive Clinical Forum on generalized myasthenia gravis and discussed how FcRn and complement inhibitors are reshaping treatment algorithms for the disease.
Earlier this month, NeurologyLive convened a Clinical Forum in Dallas titled “Navigating the Evolving Landscape of Generalized Myasthenia Gravis: Strategies for FcRn Inhibitor Therapy,” bringing together neurologists and neuroimmunologists to discuss how the treatment algorithm for generalized myasthenia gravis (gMG) has shifted since the first complement inhibitor reached the market in 2017. The conversation centered on the growing menu of FcRn and complement inhibitor therapies now available to patients with acetylcholine receptor and muscle-specific kinase antibody positive gMG, and how those options are changing the calculus around when, and how aggressively, to treat.
The forum was led by Shaida Khan, DO, associate professor of neurology at UT Southwestern Medical Center, who practices at Parkland Health in Dallas. Khan has practiced through what she describes as both the conventional and the golden eras of myasthenia treatment, and she walked attendees through the mechanisms, trial data, and real-world tradeoffs behind the current generation of targeted therapies.
In a post-forum interview, Khan looked back on that conversation for anything clinicians in attendance, or reading along after the fact, may have taken away. She discussed what feels most different about treating gMG now compared with five or 10 years ago, how she expects the next generation of neurologists to approach the disease differently than her own, and what she is most hopeful about as biomarkers and combination strategies move toward the clinic. She also reflected on a moment from the forum that, for her, captures why the work matters in the first place.
Shaida Khan, DO: With the newer therapies, even within a class, we have different options and modes of administration: IV, subcutaneous, and now, with the recent B cell depletion approval, even more variety. That changes our practice because now we have clinical trial data and FDA approval behind these drugs. Before, we had anecdotal evidence that something worked, but it took a long time, and there were a lot of adverse effects and certain risks with what I call old-school immunosuppression, which still has a role, as I mentioned at the forum.
I think our tolerance for the length of time it takes to get medications working in our MG patients has changed. Before, the timeframe we allowed for patients to continue on prednisone, then immunosuppression, or IVIG or plasma exchange, was much longer. Now we have more targeted approaches that work quickly and effectively and are safe, so we have less tolerance for managing adverse effects, or for avoiding treatment altogether. We can jump to certain agents with certain risk profiles that we didn’t have the option to use before, in a brittle diabetic patient or an elderly patient with comorbidities that previously made us hesitate to use immunosuppression or keep increasing prednisone. Having these newer options completely changes how we approach the disease, particularly at the onset of diagnosis.
It’s been exciting to see the boom in myasthenia gravis treatment over the last five to 10 years, and we anticipate it continuing. There are several other therapeutics currently in phase 2 and phase 3 studies that we’re hopeful will be approved within the next couple of years. The more options, the better for patients and what we can provide them.
As trainees learn and understand these medications, I think they’ll naturally be more inclined to reach for them as first line, rather than defaulting to the drugs those of us already in practice have more comfort level with. We still continue to deploy the older treatments and monitor patients on them, while knowing when to bring in the newer options, but we’re also thinking more about cost effectiveness. As more options evolve and some become generic, I think cost will be less of a barrier.
So, I think the algorithm for treating myasthenia is going to change, and we’re going to lean on these drugs as first line in certain populations of patients with gMG, whether MuSK or AChR antibody positive. I think the consensus guidelines that get published next are going to reflect that too. The current guidelines mention complement inhibitors, but I expect the next set to put them at the forefront.
Looking at combination therapies in certain individuals is interesting, because right now it’s still trial and error. We don’t know whether complement inhibition will work better in one patient versus FcRn inhibition. We know they’re all effective, targeted, and work well at preserving the integrity of the neuromuscular junction and improving clinical symptoms. What I’m excited about is the potential to find more tailored therapies, to say that based on a specific microRNA profile or biomarker, a given patient would probably benefit more from one approach, or that a particular IgG level correlates with higher rates of remission.
We always talk about escalating treatment, but I’m excited to see what certain profiles might let us de-escalate. Could we get patients off treatment entirely, and could we do that more confidently with certain profiles than others? That’s an unmet need for patients: they always want to know their chances of remission, and whether they’ll stay in remission if they come off treatment. I know investigators are looking at some of these questions.
We’ve seen a lot of that same shift in the multiple sclerosis field over the last several years, moving toward precision and individualized treatment. Now that we have more options for myasthenia gravis, those same conversations are starting to happen here too.
That meant everything to me. That’s why I do this. I highlighted this at the forum too: we talk so much about disease mechanisms, pathogenesis, molecular profiles, and side effect profiles, which is all very important. But at the core of everything we’re doing is the outcome for the patient, and how we can get them back to who they are, back to their social life, their work, their family. That’s why she was so emotional. She told me I gave her her life back, and that is why I do this. When I hear stories like that, it reminds me that this work is truly making a difference. There are a lot of neurological diseases where we can offer comfort but not much more. Myasthenia is one of the diseases where we can genuinely get patients back to normal functioning, and being able to tell someone, “I can get your life back,” means everything to me.
It’s a great time to be in neurology, and especially in the neuromuscular space, now that we have options to offer patients instead of just a diagnosis. It reminds me of what’s happened in multiple sclerosis, where the treatment algorithm has changed completely with the introduction of so many new therapies. The leaders in that field aren’t reaching for the older medications nearly as often anymore, because the newer drugs that once seemed high risk are proving to be lower risk than expected, and more effective. I think myasthenia care is heading in that same direction: toward deploying the more effective treatments earlier in the disease course, rather than waiting and stepping patients up through each option in turn.
Transcript edited for clarity.
