Real-world data show gMG treatment works across patient groups

Vyvgart (efgartigimod alfa) is generally well tolerated and effective for adults with generalized myasthenia gravis (gMG), regardless of the presence and type of disease-causing antibody, according to a real-world study in Japan.

The treatment, which has been approved in Japan for gMG regardless of antibody status since 2022 and expanded for that indication in the U.S. this year, reduced the disease’s impact on daily life activities and mean dose of oral corticosteroids across antibody-based subgroups.

The study, “Safety and effectiveness of efgartigimod in patients with generalized myasthenia gravis by autoantibody subtype: analysis of postmarketing surveillance in Japan,” was published in Scientific Reports. All authors were employees at Argenx, the company that markets Vyvgart.

gMG is an autoimmune disease that disrupts communication between nerve and muscle cells, causing muscle weakness across the body and fatigue. Most patients test positive for self-reactive antibodies against anti-acetylcholine receptor (AChR), while others have antibodies targeting other proteins involved in nerve-muscle communication, including muscle-specific kinase (MuSK).

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Protein blocking

Vyvgart, administered directly into the bloodstream via infusions, works by blocking a protein called neonatal Fc receptor (FcRn), which normally prevents the breakdown of circulating antibodies. Suppressing FcRn causes antibodies, including those that drive MG, to be cleared from the blood more quickly, which may help ease gMG symptoms.

In Japan, the therapy is approved for adults with gMG whose disease has not responded adequately to other treatments, regardless of their antibody status. In the U.S., Vyvgart was initially cleared for use in adults with gMG testing positive for anti-AChR antibodies. In May, the therapy’s label was expanded to include all adult patients regardless of antibody status.

A team of researchers set out to analyze the impact of antibody status on the safety and efficacy of Vyvgart in everyday clinical practice.

They analyzed data from gMG patients who received at least one Vyvgart cycle (four weekly infusions) from 2022 to 2023 as part of an ongoing post-marketing surveillance study, which is scheduled to continue until the end of 2027.

Of the 553 patients registered in the study, 473 (mean age 50.8, 67% women) were included in the analysis. More than half (56.7%) had anti-AChR antibodies, 13.3% had anti-MuSK antibodies, and 29.2% had neither (double seronegative).

Before Vyvgart treatment, the disease’s impact on daily activities, as assessed with the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, was higher in the MuSK and double-seronegative groups than in the AChR group. Participants with anti-MuSK antibodies were also more likely to be taking high-dose oral corticosteroids and to have received plasma exchange.

Corticosteroids are a type of anti-inflammatory and immunosuppressive medication commonly used in gMG, but associated with serious side effects. Plasma exchange is a procedure that aims to remove disease-causing antibodies from a patient’s blood.

People in the double-seronegative group were less likely to have severe disease and more likely to be taking low-dose corticosteroids than the other groups.

Participants were followed for a mean of nearly nine months, during which time they received a median of three Vyvgart cycles. The median interval between cycles was about seven weeks. These values were similar across the three antibody groups.

Overall, 22.6% of participants experienced at least one treatment-related adverse event, and 4.2% experienced serious treatment-related adverse events. There were no notable differences between antibody groups.

The most commonly reported treatment-related adverse reactions were symptom recurrence (21.4%) and infusion-related headache (11.9%). Infusion reactions occurred in nine participants, including one who developed a severe allergic reaction and permanently stopped Vyvgart. None of the 10 deaths was considered related to Vyvgart.

The effectiveness analysis involved 311 patients. During the first treatment cycle, the mean MG-ADL score improved by a mean of 43.9% after three weeks. Improvements were seen across all four MG-ADL subdomains: eye symptoms, swallowing and speech, limb and gross motor function, and breathing.

“These findings indicate that [Vyvgart] may represent a promising therapeutic option not only for patients with [anti-AChR-antibody] positive gMG, but also for those with [anti-MuSK antibody] positive and double-seronegative gMG,” the researchers wrote.

Among 309 participants treated with Vyvgart for more than six months, daily oral corticosteroid dose fell from 10.7 mg before Vyvgart to 7.7 mg after one year. The proportion of patients taking a 5 mg/day dose or lower increased from 27.7% to 40.8%, and that of patients taking doses higher than 10 mg/day decreased from 39.3% to 22.3%. Similar results were observed across antibody groups.

These findings “are consistent with a potential [corticosteroid]-sparing effect observed during [Vyvgart] treatment in Japanese real-world clinical practice,” the researchers wrote.

They noted, however, that because the study was observational and lacked a placebo or comparator group, further research is needed to confirm the treatment’s long-term effectiveness and safety and determine its role in reducing corticosteroid use.