6 ms·

Vagus nerve stimulation significantly reduces rheumatoid arthritis symptoms

111 points by HillaryBriss 10y ago

MrZongle2 10y ago
Vagus nerve stimulation has also been used to treat some forms of epilepsy since the late 90s, and is being researched as a treatment for a wide variety of other illnesses and conditions: https://en.wikipedia.org/wiki/Vagus_nerve_stimulation https://en.wikipedia.org/wiki/Vagus_nerve_stimulation
- etjossem 10y ago
  It's important to remember that this was never a first-choice treatment for seizures. VNS was only viewed as a worthwhile course to pursue after trying an exhaustive list of drugs. From an FDA hearing on VNS: "there were patients who were very good responders, becoming essentially seizure-free, as well as patients who were poor responders, having 100 percent or greater increase in their seizure frequency," and it was very difficult to predict how a given patient would respond. [1] [1] http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf p127
medymed 10y ago
Neurological manipulation to manage inflammatory condition may have a promising future, and may be a good avenue to pursue for some patients (like people not responding to immunomodulation). At a conference I overheard of botox injection reducing psoriasis plaques in otherwise unresponsive patients (just hearsay), and it is known that patients with onset of types of neurologic damage (e.g. Parkinsons) have increased risk of another inflammation-related condition seborrheic dermatitis (just correlation). Teasing apart causal mechanisms at work could be quite a task.
- joe_the_user 10y ago
  Well, If the electrical stimulation is effective, I would say it would probably be preferable to most drug therapies since just about all drugs have serious side-effects when taken over a lifetime - certainly mainstream rheumatoid arthritis drugs like Prednisone can have horrific side-effects.
  - tosseraccount 10y ago
    Anti-TNF biologics are a thing: https://en.wikipedia.org/wiki/TNF_inhibitor https://en.wikipedia.org/wiki/TNF_inhibitor
    - thenomad 10y ago
      And they also come with some unpleasant side-effects: a much higher incidence of skin cancer and all the risks that come with being immunosuppressed. (Plus the disadvantages - if you like soft cheese and deli meats, being on an anti-TNF drug will suck.) They're also very, very expensive.
      - jukkakoskinen 10y ago
        Can you expand on the soft cheese and deli meats claim?
        jknightco 10y ago
        Having a depressed immune system means you're more likely to contract things like listeria or toxo plasmosis which are commonly found in cured meats and soft cheeses. This is also the reason why pregnant women are advised against eating them.
        thenomad 10y ago
        Exactly so. (AFAIK Lysteria, Salmonella and E.Coli will be amongst the major risk factors.)
        matheweis 10y ago
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615849/#!po=5.98958 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615849/#!po=5.9... C diff, Lysteria, and Salmonella... Oddly, ecoli doesn't appear on the list. See table #2 & #3
    - 10y ago
sctb 10y ago
We updated the link from https://www.sciencedaily.com/releases/2016/07/160704223410.htm https://www.sciencedaily.com/releases/2016/07/160704223410.h..., which points to this.
tosseraccount 10y ago
PNAS journal link here : http://www.pnas.org/content/early/2016/06/30/1605635113.full?sid=d6b4d596-f61b-41b0-a472-cfdaa7d717e2 http://www.pnas.org/content/early/2016/06/30/1605635113.full... : "Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis". "In one circuit, termed “the inflammatory reflex,” action potentials transmitted in the vagus nerve inhibit the production of tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target in RA. Although studied in animal models of arthritis and other inflammatory diseases, whether electrical stimulation of the vagus nerve can inhibit TNF production in humans has remained unknown. The positive mechanistic results reported here extend the preclinical data to the clinic and reveal that vagus nerve stimulation inhibits TNF and attenuates disease severity in RA patients."
ofcrpls 10y ago
http://ntsconference.com/wp-content/uploads/2015/04/NTS_agenda_051816_web_full.pdf http://ntsconference.com/wp-content/uploads/2015/04/NTS_agen... My wife came out of this conference saying, everyone is just throwing everything at the wall and see what sticks with vagal nerve stimulation. Controls are minimal to none in most studies. Of course her perspective is from the regulatory side.
- cpncrunch 10y ago
  That was my conclusion when reading this study. There is basically no control at all. They say the placebo effect couldn't have affected the results when the patients were under general anaesthetic. That is certainly true, but waiting 4 hours to measure TNF could certainly have had an effect. Given that vagus nerve stimulation has failed in a placebo controlled trial for depression, I think we should be cautious about this and wait for some proper science. It irks me when people do shoddy science like this, which basically tells us nothing.
  - incongruity 10y ago
    It's actually worse than nothing. It puts an idea out there that may or may not be true, but it has the potential to get picked up by the media and/or stuck in people's minds as factual. A single paper claiming vaccines causing autism is a great example of this...
  - ars 10y ago
    > They say the placebo effect couldn't have affected the results when the patients were under general anaesthetic. That is certainly true, Is it? It doesn't seem certainly true to me. The non-conscious part of the mind can tell that "something" is being done to it, and can draw comfort from that alone.
    - cpncrunch 10y ago
      Yes, good point. I think it's wise to be skeptical about any study that isn't placebo controlled.
Jerry2 10y ago
Dr Kevin Tracey, pioneer and inventor of these methods, gave a fascinating TED talk on this topic not so long ago. If you have 15 min to spare, give it a watch... it's amazing: http://www.tedmed.com/talks/show?id=526203 http://www.tedmed.com/talks/show?id=526203
crazydoggers 10y ago
So given that the mammalian diving reflex also stimulates the vagus nerve, is anybody researching its effects on inflammation? Seems like it might be preferable to suggest swimming therapy rather than immediately jumping to surgical implants. (plus the exercise probably can't hurt) Or does the surgical implant provide stimulation in a different amount/manner than the diving reflex would?
- artifaxx 10y ago
  Especially given the cost! There are a lot cheaper ways to stimulate the vagus nerve. They could have spent more on implementing proper control groups and still saved money.
djrogers 10y ago
Is it just me or is this a press release?
- cpncrunch 10y ago
  Yes, it's the great HN tradition of posting flashy press releases claiming that someone is about to change the world, based on dubious science. I think this is the actual study: http://www.pnas.org/content/early/2016/06/30/1605635113.full http://www.pnas.org/content/early/2016/06/30/1605635113.full
stevebmark 10y ago
Interesting: "Vagus nerve stimulation inhibits cytokine production". Cytokines are "any of a number of substances...that are secreted by certain cells of the immune system" Rheumatoid arthritis is an inflammation of the joints causing pain. Inflammation is caused by your immune system to heal a problem, like a cut or an infection. This vagus nerve technique works by suppressing your immune system. I don't really know what I'm talking about here, but maybe a better path to a cure is to stop the underlying cause of the inflammation? "Doctors don’t know exactly what causes RA. It may be a combination of genes and environment" - WebMD. The body is attacking itself, finding out why sounds important to me.
- crazydoggers 10y ago
  Agreed. However, generally auto immune diseases like RA are caused by an immune system run amok. It's possible that treatments that break the cycle of the immune system overreacting can indeed result in long term alleviation of symptoms. Sometimes once the cycle is broken, remission may even occur. I have horrible seasonal allergies, and although no one really knows the underlying cause, immunization therapy via injections of antigens has results in significant reduction of symptoms. So in my case, a non drug treatment that aims to blunt the body's response has resulted in the most important treatment of my allergies, even though a "cure" and the underlying cause is not well understood.
- kirrent 10y ago
  As someone with pretty bad RA, it'd be nice if they could do that. Unfortunately, the ultimate causes behind RA are pretty obscure at the moment. While they don't work particularly well for me, cytokine inhibitors such as abatacept are one of the gold standard treatments at the moment.
carbocation 10y ago
Generally, when I see people with vagal stimulators for painful or uncomfortable conditions, it's a sign to me that they have been through many different treatments that have not been effective for them. I've never seen anyone receive these for any indication that has convinced me they are effective.
dspeyer 10y ago
Is there a good reason for making day 42 (out of 84) the primary endpoint? Did they at least decide to do that before looking at the data?
hiccupss 10y ago
Does this have anything to do with getting The Hiccups?

111 points by HillaryBriss 10y ago

Vagus nerve stimulation has also been used to treat some forms of epilepsy since the late 90s, and is being researched as a treatment for a wide variety of other illnesses and conditions: https://en.wikipedia.org/wiki/Vagus_nerve_stimulation https://en.wikipedia.org/wiki/Vagus_nerve_stimulation

etjossem 10y ago
It's important to remember that this was never a first-choice treatment for seizures. VNS was only viewed as a worthwhile course to pursue after trying an exhaustive list of drugs. From an FDA hearing on VNS: "there were patients who were very good responders, becoming essentially seizure-free, as well as patients who were poor responders, having 100 percent or greater increase in their seizure frequency," and it was very difficult to predict how a given patient would respond. [1] [1] http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf p127

medymed 10y ago

Neurological manipulation to manage inflammatory condition may have a promising future, and may be a good avenue to pursue for some patients (like people not responding to immunomodulation). At a conference I overheard of botox injection reducing psoriasis plaques in otherwise unresponsive patients (just hearsay), and it is known that patients with onset of types of neurologic damage (e.g. Parkinsons) have increased risk of another inflammation-related condition seborrheic dermatitis (just correlation). Teasing apart causal mechanisms at work could be quite a task.

joe_the_user 10y ago
Well, If the electrical stimulation is effective, I would say it would probably be preferable to most drug therapies since just about all drugs have serious side-effects when taken over a lifetime - certainly mainstream rheumatoid arthritis drugs like Prednisone can have horrific side-effects.
- tosseraccount 10y ago
  Anti-TNF biologics are a thing: https://en.wikipedia.org/wiki/TNF_inhibitor https://en.wikipedia.org/wiki/TNF_inhibitor
  - thenomad 10y ago
    And they also come with some unpleasant side-effects: a much higher incidence of skin cancer and all the risks that come with being immunosuppressed. (Plus the disadvantages - if you like soft cheese and deli meats, being on an anti-TNF drug will suck.) They're also very, very expensive.
    - jukkakoskinen 10y ago
      Can you expand on the soft cheese and deli meats claim?
      - jknightco 10y ago
        Having a depressed immune system means you're more likely to contract things like listeria or toxo plasmosis which are commonly found in cured meats and soft cheeses. This is also the reason why pregnant women are advised against eating them.
        thenomad 10y ago
        Exactly so. (AFAIK Lysteria, Salmonella and E.Coli will be amongst the major risk factors.)
        matheweis 10y ago
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615849/#!po=5.98958 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615849/#!po=5.9... C diff, Lysteria, and Salmonella... Oddly, ecoli doesn't appear on the list. See table #2 & #3
  - 10y ago

sctb 10y ago

We updated the link from https://www.sciencedaily.com/releases/2016/07/160704223410.htm https://www.sciencedaily.com/releases/2016/07/160704223410.h..., which points to this.

tosseraccount 10y ago

PNAS journal link here : http://www.pnas.org/content/early/2016/06/30/1605635113.full?sid=d6b4d596-f61b-41b0-a472-cfdaa7d717e2 http://www.pnas.org/content/early/2016/06/30/1605635113.full... : "Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis". "In one circuit, termed “the inflammatory reflex,” action potentials transmitted in the vagus nerve inhibit the production of tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target in RA. Although studied in animal models of arthritis and other inflammatory diseases, whether electrical stimulation of the vagus nerve can inhibit TNF production in humans has remained unknown. The positive mechanistic results reported here extend the preclinical data to the clinic and reveal that vagus nerve stimulation inhibits TNF and attenuates disease severity in RA patients."

ofcrpls 10y ago

http://ntsconference.com/wp-content/uploads/2015/04/NTS_agenda_051816_web_full.pdf http://ntsconference.com/wp-content/uploads/2015/04/NTS_agen... My wife came out of this conference saying, everyone is just throwing everything at the wall and see what sticks with vagal nerve stimulation. Controls are minimal to none in most studies. Of course her perspective is from the regulatory side.

cpncrunch 10y ago
That was my conclusion when reading this study. There is basically no control at all. They say the placebo effect couldn't have affected the results when the patients were under general anaesthetic. That is certainly true, but waiting 4 hours to measure TNF could certainly have had an effect. Given that vagus nerve stimulation has failed in a placebo controlled trial for depression, I think we should be cautious about this and wait for some proper science. It irks me when people do shoddy science like this, which basically tells us nothing.
- incongruity 10y ago
  It's actually worse than nothing. It puts an idea out there that may or may not be true, but it has the potential to get picked up by the media and/or stuck in people's minds as factual. A single paper claiming vaccines causing autism is a great example of this...
- ars 10y ago
  > They say the placebo effect couldn't have affected the results when the patients were under general anaesthetic. That is certainly true, Is it? It doesn't seem certainly true to me. The non-conscious part of the mind can tell that "something" is being done to it, and can draw comfort from that alone.
  - cpncrunch 10y ago
    Yes, good point. I think it's wise to be skeptical about any study that isn't placebo controlled.

Jerry2 10y ago

Dr Kevin Tracey, pioneer and inventor of these methods, gave a fascinating TED talk on this topic not so long ago. If you have 15 min to spare, give it a watch... it's amazing: http://www.tedmed.com/talks/show?id=526203 http://www.tedmed.com/talks/show?id=526203

crazydoggers 10y ago

So given that the mammalian diving reflex also stimulates the vagus nerve, is anybody researching its effects on inflammation? Seems like it might be preferable to suggest swimming therapy rather than immediately jumping to surgical implants. (plus the exercise probably can't hurt) Or does the surgical implant provide stimulation in a different amount/manner than the diving reflex would?

artifaxx 10y ago
Especially given the cost! There are a lot cheaper ways to stimulate the vagus nerve. They could have spent more on implementing proper control groups and still saved money.

djrogers 10y ago

Is it just me or is this a press release?

cpncrunch 10y ago
Yes, it's the great HN tradition of posting flashy press releases claiming that someone is about to change the world, based on dubious science. I think this is the actual study: http://www.pnas.org/content/early/2016/06/30/1605635113.full http://www.pnas.org/content/early/2016/06/30/1605635113.full

stevebmark 10y ago

Interesting: "Vagus nerve stimulation inhibits cytokine production". Cytokines are "any of a number of substances...that are secreted by certain cells of the immune system" Rheumatoid arthritis is an inflammation of the joints causing pain. Inflammation is caused by your immune system to heal a problem, like a cut or an infection. This vagus nerve technique works by suppressing your immune system. I don't really know what I'm talking about here, but maybe a better path to a cure is to stop the underlying cause of the inflammation? "Doctors don’t know exactly what causes RA. It may be a combination of genes and environment" - WebMD. The body is attacking itself, finding out why sounds important to me.

crazydoggers 10y ago
Agreed. However, generally auto immune diseases like RA are caused by an immune system run amok. It's possible that treatments that break the cycle of the immune system overreacting can indeed result in long term alleviation of symptoms. Sometimes once the cycle is broken, remission may even occur. I have horrible seasonal allergies, and although no one really knows the underlying cause, immunization therapy via injections of antigens has results in significant reduction of symptoms. So in my case, a non drug treatment that aims to blunt the body's response has resulted in the most important treatment of my allergies, even though a "cure" and the underlying cause is not well understood.
kirrent 10y ago
As someone with pretty bad RA, it'd be nice if they could do that. Unfortunately, the ultimate causes behind RA are pretty obscure at the moment. While they don't work particularly well for me, cytokine inhibitors such as abatacept are one of the gold standard treatments at the moment.

carbocation 10y ago

Generally, when I see people with vagal stimulators for painful or uncomfortable conditions, it's a sign to me that they have been through many different treatments that have not been effective for them. I've never seen anyone receive these for any indication that has convinced me they are effective.

dspeyer 10y ago

Is there a good reason for making day 42 (out of 84) the primary endpoint? Did they at least decide to do that before looking at the data?

hiccupss 10y ago

Does this have anything to do with getting The Hiccups?