LEIDEN, The Netherlands – Amifampridine, the active ingredient in Firdapse, provides meaningful clinical benefits for people with Lambert-Eaton myasthenic syndrome (LEMS), while the use of immunosuppressive therapies tends to increase as the disease progresses, according to a long-term study conducted at a Dutch medical center.
The study also found that about one in four patients had started symptomatic or immunosuppressive treatment before receiving a LEMS diagnosis, possibly because some had initially been diagnosed with another disorder with similar symptoms.
“This retrospective study provides a comprehensive longitudinal overview of pharmacological treatment patterns in LEMS,” the researchers wrote. “Amifampridine provides significant clinical benefits and remains the cornerstone of LEMS therapy.”
Study examines LEMS treatment patterns over more than 30 years
The study, “Longitudinal overview of symptomatic and immunosuppressive drugs in LEMS,” was published in the Journal of Neuromuscular Diseases.
LEMS is a rare autoimmune disorder in which self-reactive antibodies disrupt communication between nerves and muscles, causing muscle weakness. The weakness most often affects the hips and thighs, making activities such as walking and climbing stairs difficult.
About 60% of people with LEMS have an associated cancer, most commonly small cell lung cancer (SCLC). The remaining 40% have non-tumor-associated LEMS.
Researchers retrospectively reviewed medical records from 70 people with LEMS, 66% of whom were women, who had been treated by neurologists at Leiden University Medical Center (LUMC) in the Netherlands. Patients were diagnosed between 1992 and 2023 and had lived with LEMS for a median of six years. Median follow-up was nearly five years, although individual follow-up ranged from less than one month to approximately 28 years.
LUMC is a national referral center for LEMS, and most patients in the Netherlands have been treated there at some point during their disease course.
Only 23% of the patients in the study had SCLC-associated LEMS, compared with 77% who had non-tumor-associated disease. The researchers suggested this may reflect referral bias, as cancer treatment often takes priority for people with SCLC-associated LEMS, making them less likely to receive long-term neuromuscular follow-up at LUMC.
Most patients started amifampridine soon after diagnosis
All patients in the study received amifampridine at some point, and 91% started treatment within six months of being diagnosed.
At their latest assessment, 93% were using a modified-release form of amifampridine. Of these patients, 78% used the modified-release formulation alone, while 15% used it in combination with Firdapse, an immediate-release formulation.
Firdapse is an oral treatment approved for LEMS. It is approved in the European Union for adults and in the United States for patients ages 6 and older. Amifampridine works by increasing the release of the chemical signals needed for communication between nerves and muscles.
In the Netherlands, patients can receive either Firdapse immediate-release tablets or a modified-release formulation produced by the LUMC pharmacy.
To evaluate treatment response, researchers developed a four-point “leg score” based on the impact of leg weakness on daily activities. A score of zero represented no leg weakness, while a score of three indicated the need for a walking aid or significant difficulty with daily activities.
Among patients with available scores, 57% experienced an improvement in leg function after starting amifampridine. Scores decreased by one point in 48% of patients, by two points in 7%, and by three points in 2%. Overall, the improvement was statistically significant.
Similar improvements were observed in patients who had previously received, or were receiving at the same time, pyridostigmine or immunosuppressive treatment.
Patients who had tried both amifampridine formulations generally reported fewer side effects and more consistent symptom control with the modified-release version. Those who preferred Firdapse most commonly pointed to its faster onset of action.
Patients also described noticeable improvements in daily functioning. One reported being able to stand on one leg again for the first time in four years, while others described being able to walk better, sit for longer, and resume evening walks.
Side effects were common, but few stopped amifampridine
More than half of the patients reported side effects while taking amifampridine. The most common was paresthesia — sensations such as tingling or pins and needles — reported by 41.4%.
Despite this, only five patients, or 7%, discontinued amifampridine. Four of those patients stopped because they had entered remission.
Pyridostigmine was widely used but often discontinued
Pyridostigmine was used by 81% of patients at some point during their disease course. Although the medication is primarily marketed as Mestinon for myasthenia gravis, it is also commonly used off-label to treat LEMS symptoms.
Approximately one-third of patients (32%) discontinued pyridostigmine. Half of those who stopped did so because of side effects, while 39% cited a lack of clinical benefit. Gastrointestinal problems were the most frequently reported reason for discontinuation, accounting for 28% of cases.
Immunosuppressive therapy became more common over time
Unlike symptomatic treatments, the use of immunosuppressive medications increased as patients lived longer with LEMS.
Within six months of diagnosis, 23% of patients had started an immunosuppressive treatment. Among the 34 patients with five years of follow-up data, 14 were receiving immunosuppressive therapy at that point.
The most frequently used immunosuppressants were prednisolone, used by 49% of patients, and azathioprine, used by 42%.
Additionally, 30% of patients underwent plasma exchange and/or received intravenous immunoglobulin (IVIG) at some point during their disease course. Plasma exchange removes disease-driving antibodies from the bloodstream, while IVIG can help regulate harmful autoimmune activity.
Some patients were treated before receiving a LEMS diagnosis
A notable finding was that 26% of patients had already received symptomatic or immunosuppressive treatment before being diagnosed with LEMS.
The researchers suggested that these patients may initially have been diagnosed with myasthenia gravis, which can cause symptoms similar to LEMS. However, previous diagnoses were not systematically documented in the medical records, so the researchers could not confirm the reason for the earlier treatments.
Overall, the findings suggest that symptomatic treatment is generally introduced early after a LEMS diagnosis and continues throughout the disease course, while immunosuppressive therapy becomes increasingly common over time.
“Longitudinal data on medication use indicate that symptomatic treatment is typically initiated early and maintained throughout the disease course,” the researchers wrote. “Amifampridine, predominantly administered as a modified-release formulation, demonstrated clear clinical benefit, although residual functional impairments remained common.”
Contact
Wisse R. Bakker – MD, PharmD
Leiden University Medical Centre