Redefining gMG Management: Pt I

Key Takeaways

• The treatment landscape for myasthenia gravis (MG) is undergoing a renaissance, shifting from broad immunosuppression to more targeted, mechanism-driven therapies that allow for greater precision and personalization.
• Step therapy requirements may delay access to high-efficacy, disease-specific treatments, potentially affecting long-term outcomes and increasing risks such as hospitalization or intubation.
• As bispecific agents and other advanced therapies emerge, clinicians will need clear sequencing strategies and greater payer flexibility to optimize individualized care.

Amanda Hernandez, MD, PhD: Hi, I’m Amanda Hernandez. I’m a neuroimmunologist who specializes primarily in the treatment of neuromuscular diseases. My background is quite rich—I care for patients across both neuroimmunology and neuromuscular medicine within the broader discipline of neurology. That means I treat conditions such as myasthenia gravis, neuromyelitis optica, multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy.

In addition to my clinical training, I have a PhD in immunology. I’m very proud to participate in translational research, run clinical trials, and bring my knowledge of the immune system directly into my clinical practice. I often tell my patients that I “tinker with the immune system” for a living—and hopefully make a meaningful difference in their lives.

I’m also on faculty at the University of Connecticut, where I oversee the division of neuromuscular medicine. I run the comprehensive myasthenia program and am deeply involved in educating medical students, residents, and fellows. It’s a very rich and rewarding professional environment.

How are advances in immunotherapy, including bispecific approaches, reshaping long-term disease management in gMG?

Dr Hernandez: I often liken where we are in myasthenia gravis to where we were in multiple sclerosis about 10 years ago. That was when we began digging into B-cell depletion therapies and S1P modulators, and we started distinguishing between high-efficacy and low-efficacy treatments. There was a real push toward being more specific and more curated in how we approached therapy.

In myasthenia, we recognize that this is an autoantibody-driven, B-cell–mediated disease process. That gives us an opportunity to be much more targeted in our approach. We’re moving away from blanket immunosuppression—throwing a “fire blanket” over the immune system and telling it to quiet down—and instead focusing on the specific drivers of disease.

Historically, we’ve relied on prednisone, steroids, and nonsteroidal immunosuppressive therapies. But now we’re in a renaissance in the myasthenia treatment landscape. We have far more control—not just over the disease itself, but over how we control the disease. That’s incredibly empowering as a clinician, and even more empowering for patients.

How are evolving diagnosis patterns and earlier intervention changing treatment sequencing in gMG—and how should payers adapt their coverage strategies?

Dr Hernandez: In my experience, step therapy is seldom in the best interest of the patient. I practice in a state where there is some jurisdiction around step therapy, so I may not experience the same level of complexity as colleagues in other states—but I know many of them face significant challenges.

For example, requiring a patient to try and fail IVIG before gaining access to a complement inhibitor may not set that patient up for success. It essentially says, “We’re going to use an older approach first, even if there’s a more targeted therapy that could meaningfully improve your quality of life.”

What we understand about the pathophysiology of myasthenia is that the muscle membrane can sustain damage over time if disease control is delayed. While regeneration is possible, earlier and more curated intervention can better position a patient for long-term success in their treatment journey.

If we can gain control sooner with therapies designed to target the underlying mechanism, we may improve quality of life, reduce hospitalizations, and decrease the risk of complex admissions that may involve intubation. Ultimately, keeping patients as stable and healthy as possible is in everyone’s best interest—including the health care system’s.

I hope that as the treatment landscape evolves, payers will adapt in ways that allow patients access to the therapies most appropriate for them.

As targeted therapies like bispecific agents enter the market, how can payers balance innovation with sustainable access?

Dr Hernandez: When I think about bispecific agents, I think about therapies in development—such as certain CAR-T strategies and complement inhibitors engineered to target both C5 and albumin.

We’re entering a phase in myasthenia where we will need a clear roadmap for sequencing therapies. That’s a new luxury for this field. We now have multiple targeted options, but with that comes complexity. Some therapies cannot be given concomitantly. Some may be better suited earlier in disease, while others may be reserved for later lines.

No two patients are the same. They have different antibody profiles, different comorbidities, and different therapeutic responses. So we’ll need consensus and thoughtful guidance about how to sequence these therapies logically—from an immunologic perspective and from a patient-centered perspective.

Having more sophisticated therapies and broader payer flexibility expands our toolkit. But we must use that toolkit strategically.

How does the clinical heterogeneity of gMG influence real-world treatment selection, especially with newer immunotherapies and bispecific agents available?

Dr Hernandez: The more we learn about myasthenia, the more excited I become. There is extraordinary heterogeneity in this disease—not only across antibody subtypes such as MuSK, acetylcholine receptor (AChR), and LRP4, but even within those subsets.

For example, some AChR antibodies are IgM rather than IgG. We’ve also learned that antibody profiles can evolve over time. A patient’s immunologic signature at one moment may not look the same two or three years later.

We know AChR antibodies can block, bind, and modulate receptors. But we don’t always know the extent to which they are engaging complement or how those mechanisms shift over time. Certain therapies may be less effective in IgM-driven disease compared with IgG-mediated processes.

I would like to imagine a future where we can interrogate autoantibodies more deeply—understanding not just their presence, but their functional behavior. That could allow us to make highly educated, fine-tuned treatment decisions.

One of the most elegant aspects of treating an autoantibody-driven disease is that those antibodies can tell us a great deal—if we know how to listen. And learning to interpret those signals more precisely could drastically change outcomes for our patients.