Myasthenia Gravis Treatment: Eculizumab & Ravulizumab

Illustration of two medical vials labeled "Eculizumab" and "Ravulizumab," representing treatments for myasthenia gravis.
Cutting-edge research explores the efficacy and benefits of Eculizumab and Ravulizumab in treating refractory myasthenia gravis.

A recent study found that myasthenia gravis treatment with eculizumab (Soliris; Alexion) is a useful long-term option for patients with generalized myasthenia gravis (gMG) that is refractory to conventional therapy and has acetylcholine receptor (AChR) positivity.

Additionally, the study discovered that patients who transitioned from eculizumab to ravulizumab (Ultomiris; Alexion) experienced similar results. The Annals of Clinical and Translational Neurology published a report on the study.

According to the study’s authors, corticosteroids, steroid-sparing immunosuppressive therapy, and quick fixes like plasmapheresis and intravenous immunoglobulin are typically used to treat GMG. Nonetheless, they stated that 15% to 25% of gMG patients will not benefit enough from those treatments. They went on, “Myasthenic crises, hospitalizations, MG exacerbations, and a limited quality of life are characteristics of refractory disease.”

Eculizumab, a crucial myasthenia gravis treatment, is a humanized monoclonal antibody targeting human terminal complement protein 5 (C5), showing safety and efficacy in refractory gMG cases.

“Ravulizumab is a humanized monoclonal antibody partly modified from eculizumab with C5 inhibitory effect in the same way,” the authors said. “Ravulizumab has been developed using Xencor’s antibody half-life prolongation technology, which utilizes antibody Fc variants to prolong half-life.”

Long-term outcomes for patients who stop using eculizumab are unknown, though.

In the new study, individuals with AChR gMG who were treated with eculizumab, including those who switched to ravulizumab, were identified utilizing a Japanese MG registry. To monitor patient progress, they administered the MG Activities of Daily Living (MG-ADL) evaluation. Additionally, they polled patients regarding their preference for ravulizumab versus eculizumab.

The researchers discovered 36 patients who received eculizumab out of the over 1100 patients in the registry; the patients’ mean treatment duration was 35 months.

The researchers pointed out that Japan has regulations dictating which MG patients are eligible to get eculizumab.

“Japanese guidelines for MG recommended that eculizumab should be used only when management of MG is difficult despite intravenous immunoglobulin and plasmapheresis in addition to steroids and immunosuppressive drugs,” they declared. They said that as a result, the therapy was only applied to severe and unresponsive cases of MG.

Suzuki et al. observed that eculizumab improved MG-ADL scores from a mean (SD) of 9.4 (4.9) to 5.9 (5.1) in 25 of the gMG patients.

The eculizumab medication was discontinued by thirteen patients. Two of the patients—a stroke victim and a cervical cancer patient—died, but they had previously reacted to the treatment. Six patients stopped because it was effective.

Overall, ravulizumab was substituted with eculizumab in fifteen individuals. According to the authors, those patients responded well to ravulizumab, with MG-ADL scores of 6.2 (4.7) at the beginning of treatment and 5.9 (5.1) after 26 weeks.

Nine out of the fourteen patients who answered the surveys stated that they preferred ravulizumab because of its greater convenience and improved quality of life.

According to the researchers, eculizumab appears to be more beneficial for patients with early-onset MG than for those with late-onset MG or MG linked to thymomas. They suggested that one explanation could be the increased risk of severe MG in people with early-onset MG. They did note, nevertheless, that postmarket assessments conducted in Japan revealed eculizumab worked best for MG linked to thymomas.

Nonetheless, due to the long-term effects of the illness and the advantages of treating it well, the authors recommended that younger patients be given eculizumab preference.

For more information: Real-world experience with eculizumab and switching to ravulizumab for generalized myasthenia gravis, Annals of Clinical and Translational Neurology,  https://doi.org/10.1002/acn3.52051

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