LEMS Prevalence in U.S. Similar to Europe, Large U.S. Study Reports

LEMS Prevalence in U.S. Similar to Europe, Large U.S. Study Reports

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 Firdapse38%), 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.

13 comments

  1. Denise Dutwiler says:

    Ana,
    Firdapse is NOT the best treatment for LEMS, it is the ONLY treatment available after it was approved by the FDA and priced at over $375,000 a year. The same drug was available FREE for the last 30 years. I am a LEMS patient.

    • Ana Pena says:

      Hi Denise,

      Thank you for your comment and for reading our news. In this study, the authors refer to different approaches, including Mestinon (pyridostigmine), 3,4 DAP (now sold as Firdapse), glucocorticoids, and intravenous immunoglobulin (IVIG) as “therapies”. In fact, according to Muscular Dystrophy Association, all of these are considered medical management options for LEMS, as you can confirm here: https://www.mda.org/disease/lambert-eaton-myasthenic-syndrome/medical-management.

      As you said, Firdapse is the only FDA approved treatment specifically intended for LEMS, but the others are used for the management of this disease too.

      I would also like to add that Lambert-Eaton News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment and you should never disregard professional medical advice or delay in seeking it because of something you have read on this website.

      My aim is to communicate, the best as I can, the recent scientific findings regarding LEMS. These findings have been obtained and published by scientists other than me. I was not involved in the studies I write about.

      Kind regards,

      Ana

  2. Ginny Boynton says:

    Ana,
    Do you know whether the study was run with Firdapse or 3,4 DAP? Are you able to share the study with me or give me a link to access it?
    Ginny

    • Ana Pena says:

      Hi Ginny,

      Thank you for reading our news. In the study researchers only mention the chemical name “3,4-diaminopyridine (3,4 DAP)”. I referred to Firdapse, considering that, as you know, this is the brand under which the compound is currently sold in the U.S. and EU.

      This study was an observational study, which means there were no interventions made in patients. It evaluated how often 3,4 DAP (the active ingredient of Firdapse), and other medical management options, were used and what was the therapeutic response, among patients within the Veterans Affairs (VA) population from 10/1/1999 to 9/30/2013. The study was not a clinical trial directly testing Firdapse efficacy or safety in patients.

      The authors to not clarify whether they were studying the use of 3,4 DAP base formulation – the one formerly available for free, through compassionate use programs – or the commercial phosphate salt formulation (Firdapse). But considering they were analyzing registries up to 2013, it is likely many were taking the free base formulation. However, it is not specified in the paper how many of the analyzed patients were taking one versus the other and what were their outcomes.

      You can find more information about the 3,4 DAP, the active ingredient of Firdapse, here: https://www.drugbank.ca/drugs/DB11640.

      Yes, I can send you the full article by mail. I hope this information was helpful, feel free to ask any other questions,

      Kind regards,

      Ana

  3. Ginny Boynton says:

    Actually I see the article is from Muscle and Nerve magazine, but I can’t access it. Would you be able to share it? I am a LEMS patient.

    Ginny

  4. Vickie Moored says:

    I have been on 3,4 DAP and firdapse for LEMS. My body says they are not exactly the same medicine. I am weaker on firdapse then on LEMS. I wish they would chemically study what is exactly in each one.

    Vickie

  5. Ann Schuller says:

    Why is this news now? Pardon my skepticism, but why is a 3 year old VA study suddenly newsworthy? My son was diagnosed with LEMS at age 18 and responded very well to 3,4 DAP and Mestinon. As you probably know, DAP was available for free for close to 30 years under the FDA’s compassionate use program. It proved to be ave and effective for hundreds of LEMS patients. I think is odd the results of this study are reappearing just five months after Catalyst Pharmaceuticals’ drug Firdapse received FDA approval for the treatment of LEMS. Firdapse is virtually identical to DAP. While DAP was free to my son, Firdapse now costs our insurance company half a million dollars a year. Let’s get all facts on the table.

    • Ana Pena says:

      Hi Ann,

      Thank you for your comment. Unfortunately, the scientific studies on LEMS are not as frequent as we wished, therefore, sometimes, we choose to inform our readers about prior studies, provided they are not too old, rather than letting them without any scientific news for a long time. Yes, 3,4 DAP was available as a base formulation, Firdapse has the same active ingredient, but is prepared in a different formulation, a phosphate salt 3,4 DAP. In the study, researchers looked at VA LEMS patients registered from 1999 to 2013. They don’t clarify whether they were looking at people taking the base or the phosphate formulation of 3,4 DAP, even though, given the dates, most probably many were taking the base formulation. Please also read my updated comment to Ginny Boynton.

      Kind regards,

      Ana

  6. Ginny Boynton says:

    Ana,
    Thank you for sending me the Muscle and Nerve article. I believe your article should be corrected as the study specifically references that those with LEMS in the study were utilizing 3,4 DAP as an IND or compounded. They were not using Firdapse.

    I was one of the many (approximately 300 people) who used DAP safely and for free for almost 18 years only to have the price of my medicine become $500,000 annually. The announced $375,000 annual price is for what Catalyst considers its average dose of 60 mg. while I always took 90 mg. of DAP. Catalyst’s only claims as to why Firdapse is a better medication than DAP is its alleged shelf stability because of the added phosphate salt, and yet it states that the optimal temperature for its storage is 58-75….with occasional excursions at higher and lower temperatures. However, I packed a month of DAP at a time into my medication holders for each day, and never refrigerated it other than what I was not using for that month.
    Similarly, there are health reasons why it is deleterious to take medicine with phosphate salt added, and the FDA is specifically requiring Catalyst to do further trials on Firdapse’s impact in cardiac, pregnancy and hepatic/renal issues because of the phosphate salt.

    • Ana Pena says:

      Ginny,

      Thank you for calling my attention to this issue. Usually, in our news, we refer to the name of the medicine (after identifying the name of the active ingredient) to facilitate the reading as this is the name by which the compound is mostly known. But thanks to your warn, I realize this is not the case for LEMS. So I changed the text as you suggest.

      However I maintain the study does not clarify if patients were using just 3,4-DAP base formulation and not using Firdapse. It states “Given that 3,4-DAP was not approved during the study period, recipients had to receive the medication through either Investigational New Drug (IND) holders or compounding pharmacies”. Thus, the report does not specify if and how many patients received one or another and what were their specific outcomes. I’m considering here that IND was most probably Firdapse and compounded formula was the base version, available under compassionate use.

      I’d also like to add that, as our disclaimer states, Lambert-Eaton News is strictly a news and information website about the disease.

      Kind regards,

      Ana

      • Ginny Boynton says:

        We understand that it is a news and information website but want to make sure those reading are aware of the issues surrounding 3,4 DAP and Firdapse. The formulaic descriptor for Firdapse is 3,4 DAPP so presumably a study of this magnitude would have referred to the medication by 3,4 DAPP if they used Firdapse rather than 3,4 DAP.
        As I tried to state previously, the only claim Catalyst makes regarding Firdapse being a better medicine than DAP is the fact that it added phosphate salt to make it shelf stable. However, it indicates the preferred range of temperatures in which it should be stored is 68-75 with occasional excursions at higher and lower temperatures. I didn’t refrigerate my DAP after I would pack a month at a time other than what was stored for future usage and never had efficacy issues. So my annual cost went from $0 to $500,000 for my 80 mg. dose of Firdapse. I took 90 mg. of DAP for almost 18 years. 18 years of totally free medication. “Something” is wrong with our system.

  7. J Arlowe says:

    I wonder if you or anyone else at your publication will be looking for the truth and the hard facts behind FIRDAPSE. The truth is doesn’t work for a large number of LEMS patients and no one seems to care or want to know why.

    $375,000 for a drug that doesn’t work properly and was supposedly going to save LEMS patients after it was consistently marketed as a “new” treatment for LEMS.

    How do I know this? I have LEMS and advocate for over 200 people in the US who have LEMS. Your article enrages us all. Who will help us?

  8. J Arlowe says:

    Will you or anyone care enough to write the truth and present the facts about this drug?

    That Firdapse does not work for numerous LEMS patients and no one can tell us why? That so many patients have reported to the FDA but not one has had a reply promising action? That LEMS patients in the US are having to revert to or commence far more invasive treatments to stop their decline?

    That this drug has cost insurance companies and charities in the US tens of millions of dollars and it doesn’t work properly?

    That FIRDAPSE was boycotted by the UK because doctors wrote to parliament stating it had no benefit or clinical superiority over 3,4 DAP?

    How do I know this? I have had LEMS for 14 years and been a global advocate for LEMS patients for almost as long.

    Every day I read heartwrenching accounts of struggle and demise due to the inefficacy of FIRDAPSE with a handful of rare exceptions.

    Who will help us?

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