Lambert-Eaton myasthenic syndrome (LEMS) has a similar prevalence and incidence in the U.S. compared with European populations, and most patients get better with therapy, particularly with 3,4-DAP – the active ingredient in Firdapse – a nationwide study using patient data from Veterans Affairs (VA) reports.
LEMS patients diagnosed with small-cell lung cancer take less time to be diagnosed with LEMS compared with those without this cancer, which may delay treatment.
The study, “Lambert-Eaton myasthenic syndrome (LEMS): epidemiology and therapeutic response in the national Veterans Affairs (VA) population,” was published in the journal Muscle & Nerve.
Very few studies have determined the distribution of LEMS, a rare autoimmune and neuromuscular disorder, within the population.
The three existing studies have looked at disease prevalence in populations within the Netherlands and Denmark, and only one was nationwide (Netherlands).
Researchers conducted a large study to determine LEMS prevalence, incidence, patient characteristics, and treatment responses in the U.S. To do so, they queried medical records of Veterans Affairs patients registered from October 1999 to September 2013 — 12,523,409 patients.
The VA health information system, VistA, is the largest electronic medical record in the U.S.
Among this population, researchers identified 48 patients with LEMS and nine likely cases.
This gives a point prevalence (the frequency of a disease at a given time) estimate of 2.6 cases per 1,000,000 people if considering only confirmed diagnosis; 3.3 cases per 1,000,000 people including both confirmed and probable cases.
A rough incidence (the number of new cases in a population within a specified time) was estimated at 0.6 and 0.7 per 1,000,000 people per year, respectively.
Mean age at symptoms’ onset was 60 years, and mean time to diagnosis was about 10 months.
Most (33 patients, 83%) had antibodies targeting voltage gated calcium channel (VGCC), a common mark of LEMS.
Weakness in proximal muscles (those closest to the body’s midline, e.g. upper legs and hips) was the most common symptom, present in the majority of LEMS patients, followed by eye problems, bulbar symptoms (e.g. problems chewing, swallowing, and breathing) and deficiencies in gait.
More than half the confirmed patients (28 patients, 58%) had small-cell lung cancer (SCLC) at some point. Many of those (61%) were diagnosed almost simultaneously with both conditions — the detection of one led to the diagnosis of the other.
The most common medications prescribed to LEMS patients were Mestinon (pyridostigmine, 73%); 3,4-DAP (also know as amifampridine, the active ingredient in Firdapse; 38%), glucocorticoids, 35%, and intravenous immunoglobulin (IVIG, 27%).
Most patients (80%) under treatment experienced some improvement.
But from all the reported therapies, 3,4-DAP was the one resolving (1 out of 18) or relieving (13 out of 18) symptoms in more patients.
The FDA approved a phosphate formulation of 3,4-DAP, under the brand Firdapse, in November 2018 for adults with LEMS, making it the first treatment specifically indicated for the disease in the U.S.
It is a potassium channel blocker that works by increasing the release of acetylcholine, a chemical messenger (neurotransmitter) used by nerve cells to activate muscles. The medication has been shown to bring significant benefits, such as improving muscle strength, mobility, and muscle electrical activity, and it is well-tolerated.
Six patients were treated by plasma exchange (plasmapheresis) — the temporary removal of antibodies from the blood — which led to improvements in all, but this sample is too small to compare the treatment’s effectiveness with other interventions, the authors said.
This study agrees with other international studies, including a nationwide survey in the Netherlands regarding the prevalence and incidence rates of LEMS.
“However, these estimated rates based on confirmed cases likely underestimate the true prevalence and incidence of LEMS,” researchers noted.
There are a number of indeterminate cases (23 in this study) that, if corresponding to true LEMS, mean the prevalence/incidence is higher.
Also, many cancer patients may never be diagnosed with LEMS, as symptoms of muscle weakness might be misattributed to chemotherapy or cancer itself.
The study also “confirms the prominent role” of 3,4-DAP as a “leading treatment modality” for LEMS, researchers stated.
An important observation was that LEMS patients without SCLC took on average more than a year longer to be diagnosed with LEMS than those with the cancer.
“This is at least partially due to the association between SCLC and LEMS being well-known among both neurologists and oncologists.” researchers said.
This suggests that many LEMS patients without SCLC “lose the opportunity to be treated early in their disease with [3,4-DAP]”.
Despite being the largest study to date surveying LEMS in the U.S., researchers note that some facts may have introduced biases, including the fact that nearly all VA patients are men, and many are cigarette smokers, a group at higher risk of SCLC.