Non-responder to Biologics
Nicholas Silvestri, MD, FAAN, reviews investigational agents and ongoing studies in the pipeline, as well as advice for earlier engagement and evaluation of patients for myasthenia gravis to hasten treatment.
Nicholas Silvestri, MD, FAAN: This is a very exciting time in myasthenia gravis [MG]. We’ve talked about some of the agents that were recently approved, but there are others in the pipeline. There are other FcRn [neonatal Fc receptor] antagonists that are being looked at, such as rozanolixizumab, batoclimab, and nipocalimab. I’d already mentioned a novel complement inhibitor called zilucoplan, which is a subcutaneously administered complement inhibitor. I know that there has been very early work on other complement inhibitors, some subcutaneously administered and some even orally administered. Then there are other agents with completely different mechanisms of action. There are agents looking at stem cell therapies, different B-cell therapies, IL-6 antagonists, as well as BTK [Bruton tyrosine kinase] inhibitors. Finally, April technology is being looked at in myasthenia gravis as well. So, a number of different very promising forms of immunotherapy coming down the pipeline to treat our patients with MG who might otherwise have a high treatment burden or high disease burden.
Other areas of active research, besides biologics or therapeutics, include looking for biomarkers to not only predict disease course but response to therapy. So, biomarkers is another area outside of therapeutics that is being looked at.
My advice to neurologists and practitioners regarding diagnosing myasthenia gravis is you have to have a high index of suspicion for the disease. If patients come to you with weakness that fluctuates or they’re fatigue-able that’s worse with activity, particularly that which involves the eyes, bulbar muscles, and proximal limb muscles, think about myasthenia gravis. Antibody testing for acetylcholine receptor antibodies is widely commercially available and results usually come back fairly quickly. There are even some labs that will reflex it to MuSK [Muscle-specific tyrosine kinase]. But if you’re in trouble with a patient, you’re not sure what’s going on, or you have the diagnosis of myasthenia gravis and want a helping hand, then I think a quick referral to a neuromuscular neurologist is a wise decision, because, as we talked about, earlier diagnosis and earlier treatment lead to better outcomes in our patients.
Transcript edited for clarity.
