The Role of Monoclonal Antibodies in the Treatment of Myasthenia Gravis


A. Gordon Smith, MD, FAAN, considers how rituximab and eculizumab fit into the current standard of care for myasthenia gravis.

A. Gordon Smith, MD, FAAN:We are fortunate in treating patients with myasthenia gravis to now have access to a number of monoclonal antibodies that are very exciting, and each comes with opportunities and perhaps questions. One that's been around for a while and about which we certainly have questions, is rituximab, which is a B-cell-depleting antibody. The extent to which rituximab works for myasthenia gravis is in question regarding acetylcholine receptor antibody myasthenia. There's pretty good evidence that rituximab is an effective therapy for MuSK myasthenia. In acetylcholine receptor antibody-positive myasthenia, there was a negative trial called the BMG trial that was performed in the United States via the Neuro Next network. That is actually really interesting trial that has a number of lessons but what I think is interesting is a more recent trial called the RINOMAX trial that was performed in the Netherlands. RINOMAX enrolled patients with myasthenia who had symptoms of generalized myasthenia for 12 months or less. Interestingly, the response in that trial seemed to be very promising, which raises the question of whether B-cell depletion is something that might work more effectively early in the disease course. I think of the comparison here with multiple sclerosis, where there now is a thought that perhaps earlier aggressive disease modification might be very helpful. We don't yet know that for certain, so I think the question of what role rituximab plays is somewhat up in the air. There are some myasthenia experts who use a lot of it. There are others who do not and I'm hopeful that we'll have better data regarding this idea of early aggressive therapy.

Eculizumab has great data suggesting that's an effective agent. This is a complement inhibitor. The challenges in using eculizumab one is that you need to vaccinate patients for meningococcus because clearance of meningococcal bacteria is highly dependent on complement and if you inhibit complement, patients have a higher risk of these infections, which can obviously be very, very risky or life-threatening. Patients need to be vaccinated. This is not a huge problem, but something one needs to be mindful of. It is an infusion that's every 2 weeks. Ravulizumab is a little longer lasting; both are well tolerated. What role eculizumab plays, as I've mentioned already, is somewhat up in the air. The clinical trial of eculizumab really targeted patients who were refractory and that is that they had not had adequate response to corticosteroids or immunosuppressant therapies, and certainly that is I think the sweet spot for many of these new agents, although the extent to which we'll be using eculizumab or rituximab in milder disease earlier on remains to be seen with real-world experience.

Transcript edited for clarity

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