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.
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.
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...
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?
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.
"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."
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.
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.
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.
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
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]
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.
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.
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.
They definitely do cause issues - higher risk of exciting cancers and a generally more sickly existence. Studies in IBD have their efficacy at 20-30% of patients in remission after a year so they're only somewhat effective (vs half that for placebo). Anecdotally (from my own experience, and from talking to my doctors) quality of life can be poor - mind crushing fatigue is fairly common. Admittedly the fatgue may be the cocktail of other crap in my body!
Something new with few side effects might help lots of people avoid surgery.
Sorry to hear of your experience, but wanted to say for others that autoimmune diseases and the associated medications are complex beasts and ymmv...
I have been on a TNF-a inhibitor for over a year and the results thus far have been literally life changing - for the better. I haven't been this healthy or had this much energy since before adulthood.
In the US anti-TNF biologics treatments can cost several thousand dollars per month. Even with patents expiring this year the industry isn't expecting dramatic price drops due to the different regulatory process for bio-similars versus a typical generic drug.
I'm sure there are many patients who would be happy for a more cost effective option.
"several thousand" is "list price" for single shots and no or fake health insurance.
In practice insurance companies negotiate the price down and average patient pays much less than that.
Major drug makers are ready to go the second the patents expire. Prices should drop dramatically for something like Humira (adalimumab) and biosimilars.
Major problem with generic biomimetics is that without the feedstock creating infliximab etc a generic's -mab is actually going to hit the receptor in a different way, and there is some evidence (sorry, on mobile and on holidays, don't have the resource available) that such 'generics' will actually function differently.
Interesting question is whether they then need to go through the process of FDA/similar approval.
The cost savings aren't as simple as just creating the chemical structure... We are talking about immunoglobulins
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.)
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.
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:
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.