Madrid, Spain – An off-label treatment with subcutaneous efgartigimod helped manage severe, treatment-resistant Lambert-Eaton myasthenic syndrome (LEMS) in a 20-year-old woman in Spain whose condition had left her unable to walk independently or perform basic daily activities. Following treatment, she regained significant mobility and independence, eventually walking 200 meters (656 feet) without assistance, according to a case report published in Frontiers in Immunology.
The woman received Vyvgart Hytrulo, the under-the-skin formulation of efgartigimod marketed by Argenx. The medication is approved for myasthenia gravis (MG), another autoimmune neuromuscular disease, but is not approved for LEMS.
The researchers described the case in a report titled “Case Report: Efgartigimod in refractory non-tumor Lambert-Eaton myasthenic syndrome.” They believe it provides the first published account of successful efgartigimod treatment in a patient with non-tumor-associated LEMS following years of disease progression and inadequate responses to conventional immunosuppressive therapies.
The findings suggest that targeting the immune mechanisms responsible for LEMS may offer benefits to patients whose symptoms remain poorly controlled despite multiple treatments. The researchers also emphasized that prolonged disease duration should not automatically rule out targeted therapy.
Two years of progressive weakness before diagnosis
The woman initially sought medical care after experiencing months of worsening leg weakness that made running and climbing stairs increasingly difficult. Over time, the weakness spread to her shoulders and arms and became more pronounced with sustained physical activity.
A neurological examination revealed weakness in her leg and neck muscles, reduced reflexes, and mild drooping of one eyelid. Initial tests suggested a problem with communication between nerves and muscles, although blood tests for antibodies associated with MG were negative.
She was initially treated with pyridostigmine and prednisone, an immunosuppressive medication, but experienced only mild and inconsistent improvement. Her symptoms continued to worsen, eventually preventing her from carrying out basic daily activities or walking 100 meters (328 feet) without assistance.
Further testing revealed abnormal electrical responses characteristic of LEMS and antibodies targeting voltage-gated calcium channels, which interfere with nerve-to-muscle signaling. These findings confirmed the diagnosis approximately two years after her symptoms began.
Repeated imaging examinations found no evidence of an underlying cancer, establishing that her LEMS was not associated with a detected tumor.
Multiple treatments failed to provide lasting control
LEMS is an autoimmune disorder that disrupts communication between nerve and muscle cells, resulting in muscle weakness and other symptoms. Although many cases are associated with an underlying cancer, non-tumor-associated LEMS also occurs.
Treatment typically focuses on addressing any underlying cancer when present and improving neuromuscular function. Firdapse (amifampridine) is an approved treatment for LEMS, while other medications, including therapies used for MG, may be prescribed off-label.
Despite receiving Firdapse, immunosuppressive medications, and plasma exchange — a procedure that removes and replaces the liquid portion of the blood — over approximately three years, the woman continued to experience progressive disability without sustained clinical improvement.
Given the limited effectiveness of previous treatments, her healthcare team turned to efgartigimod.
Efgartigimod was associated with improved mobility and breathing
Efgartigimod works by blocking the neonatal Fc receptor (FcRn), a protein involved in maintaining antibody levels in the bloodstream. By accelerating the breakdown of circulating antibodies, the treatment may reduce the autoimmune activity responsible for neuromuscular dysfunction.
The woman continued taking Firdapse and pyridostigmine while receiving subcutaneous efgartigimod at a dose of 1,000 mg once weekly for four weeks.
After the first treatment cycle, she was able to walk longer distances and perform daily activities more easily.
Approximately two months later, before her next treatment cycle, she was hospitalized following a severe worsening of symptoms accompanied by breathing difficulties that required noninvasive respiratory support.
Efgartigimod was restarted during hospitalization. Her condition improved rapidly, allowing her to discontinue respiratory support. Subsequent treatment cycles were adjusted according to her clinical response, with the schedule eventually shortened to weekly dosing.
Assessments conducted after treatment doses showed improvements in daily functioning and reductions in scores on a validated measure of muscle weakness. By her last assessment, she could walk 200 meters without assistance and had regained the ability to independently perform more complex self-care activities.
Findings support further investigation of targeted therapy
Both LEMS and MG are autoimmune diseases that impair communication between nerves and muscles, although they involve different underlying mechanisms and clinical features. Efgartigimod’s ability to reduce circulating antibodies provides a rationale for investigating its potential in LEMS.
A previous case report described clinical improvements in an older man with LEMS associated with lung cancer who received intravenous efgartigimod. The new report adds evidence from a patient whose disease was not associated with a detected tumor and whose symptoms had remained difficult to control despite multiple treatment strategies.
The researchers concluded that their findings support further investigation of FcRn inhibition as a potential treatment approach for treatment-resistant LEMS, regardless of tumor association.
However, this report describes the experience of a single patient. Larger clinical studies are needed to establish the treatment’s safety, effectiveness, and optimal dosing schedule in people with LEMS.
Contact
Ana Baltasar-Corral
Hospital Universitario Ramón y Cajal