MuSK-MG more common in women in Japan, and often difficult to treat

Anti-MuSK antibodies rare among patients there, found in 3% of registry group

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

Share this article:

Share article via email
A doctor consults with a patient in an examining room.

Myasthenia gravis (MG) caused by the presence of self-reactive antibodies targeting muscle-specific kinase (MuSK) affects mostly women in Japan, leading to generalized muscle weakness, particularly in the face and neck, a study reports.

About half of 50 study patients had refractory MG, meaning they failed to respond to standard treatments.

“The outcomes for MuSK-MG patients in Japan are not favorable, indicating the need for more aggressive treatment,” the researchers wrote.

The study, “Clinical features and outcomes of patients with muscle-specific kinase antibody-positive myasthenia gravis in Japan,” was published in the Journal of Neuroimmunology.

Recommended Reading
Three people are shown looking at the screen of a computer tablet.

MG and its symptoms seen as harder on women, seronegative patients

Likely outcomes for MuSK-MG patients in Japan poorly understood

An autoimmune disease, myasthenia gravis is caused by self-reactive antibodies that mistakenly attack proteins important in nerve-muscle communication. Acetylcholine receptors (AChRs) and MuSK are the most common targets of MG-driving self-reactive antibodies.

Unlike in Western countries where anti-MuSK antibodies are found in 30% to 60% of MG patients lacking anti-AChR antibodies, these antibodies are less common in Japan. Anti-MuSK antibodies were found in 3% of the 1,710 MG patients enrolled in the 2021 Japan MG Registry Study Group.

As a consequence, likely long-term outcomes for these people remain poorly characterized.

Researchers at centers across Japan evaluated the disease’s characteristics and course in 51 generalized myasthenia gravis patients who tested positive for anti-MuSK antibodies.

Most (90%) were women, and the group had a median age of 35.5 at disease onset. But onset was at significantly older ages in men, a median of 58 years.

Almost all patients (98%) had bulbar symptoms — those involving the muscles in the face and neck, likely to cause difficulties with swallowing and speech. Myasthenic crises, episodes of worsening muscle weakness leading to respiratory failure, were experienced by eight patients (15.7%).

The most frequently administered therapies were prednisolone (96.1%) and immunosuppressants (84.3%). Intravenous immunoglobulin (IVIG) was given to 18 patients (35.3%), plasma exchange to 22 (43.1%), and into-the-vein methylprednisolone to 28 (55%).

Four patients received rituximab, a therapy designed to lower the numbers of antibody-producing immune B-cells, which is “widely known to be effective for the treatment of MuSK-MG,” the researchers wrote. “The widespread adoption of rituximab treatment for MuSK-MG is extremely important for improving outcomes in Japan.”

Three were given an inhibitor of the neonatal Fc receptor, a protein that helps stabilize and prevent the destruction of antibodies circulating in the bloodstream. Of note, Vyvgart (efgartigimod alfa-fcab) works to block this receptor and was approved in Japan for generalized MG patients regardless of antibody status in January 2022.

52% of MG patients with anti-MuSK antibodies had refractory disease

A total of 52.9% achieved a state of minimal disease manifestation or better after treatment. This contrasts with 73% of MG patients in the Japan 2021 registry who, regardless of antibody status, attained minimal or better disease manifestation, the researchers wrote.

About half of the patients (26 of 50 people, 52%) met the criteria for refractory MG, defined as those whose symptoms are not well controlled or who cannot tolerate MG therapies due to side effects or treatment burden.

Those with refractory MG were younger at the time of disease onset and had significantly more severe disease, as assessed by the quantitative MG score (QMG) and the MG Activities of Daily Living (MG-ADL) scale, than nonrefractory patients.

Throughout treatment, oral prednisolone doses always were significantly higher in patients with refractory MG. A larger proportion of refractory MG patients received IVIG (57.7% vs. 12.5%) and plasma exchange (61.5% vs. 20.8%) than those with nonrefractory disease. All treated with rituximab or a neonatal Fc receptor inhibitor were refractory patients.

Overall, this study found a high number of refractory MG patients who are positive for anti-MuSK antibodies.

“If this is due to the infrequency of rituximab use in Japan, aggressive immunotherapies, including biological drugs, are expected to achieve a favorable prognosis for MuSK-MG,” the researchers wrote.