An accidental discovery within a Long Island, N.Y., health system has led to the creation of a medical treatment that has the potential to replace billions of dollars of drugs with less expensive implantable devices.
The still-experimental treatment involves the transmission of electrical pulses in the nerves and, if proven effective and safe, could transform the care of patients who suffer from such conditions as rheumatoid arthritis and inflammatory bowel disease. It’s all part of the emerging field of bioelectronics.
The devices also could eat into the costs of treating various diseases, which in the case of rheumatoid arthritis alone has been estimated to total $22 billion per year.
“I think it is likely that in our lifetime — not in some distant future tense — many drugs used today will be either supplemented or replaced by bioelectronic devices,” says Kevin Tracey, M.D., president and CEO of the Feinstein Institute for Medical Research and the scientist who made the discovery.
Working at the institute, part of the North Shore-LIJ Health System, Tracey’s neurological research on the human brain unexpectedly led in 1998 to the identification of a physiological relationship between the brain and the body that previously was unknown. The nervous system is hardwired to the immune system, and the brain is in control, Tracey says.
So, in the case of a person with rheumatoid arthritis, the brain likely is sending electrical impulses that activate the immune system improperly or unnecessarily — for whatever reason — leading to the swollen joints caused by the disease. The way to treat the disease would be to electronically tell the spleen to not cause the inflammation.
A procedure to do that is being commercialized by a company Tracey co-founded, SetPoint Medical, and its scientists have shown some success in implanting devices that manipulate those electrical signals to prevent or limit the inflammation for rheumatoid arthritis.
Trials began last year to treat inflammatory bowel disease. The first round with humans involved eight patients, two of whom experienced remission from rheumatoid arthritis and six of whom had a positive response, according to SetPoint.
An alternative to drug therapy couldn’t come too soon for the 1.3 million Americans who have rheumatoid arthritis. They suffer from what can be a painful and disruptive condition and often have to pay large co-payments for access to some of the stronger drug treatments, known as biologics.
The biologic medicines can lead to skin reactions at the site of injection, and they increase the risk of all types of infections, including tuberculosis, according to the American College of Rheumatology.
Costs also are a major issue. A recent study found that Medicare patients who start using a single, biologic disease-modifying, anti-rheumatic drug, or DMARD, face an average co-pay of $2,700 each year under Medicare Part D for prescriptions that can cost close to $20,000 or more a year.
Published in the ACR journal Arthritis & Rheumatology, the study found that patients are on the hook for 29 percent of the costs until the costs reach the catastrophic coverage breakpoint in Part D, creating a barrier to treatment. “High drug costs are a significant problem, because they may limit adherence and put an enormous financial strain on patients,” says the study’s lead author Jinoos Yazdany, M.D., associate professor in the division of rheumatology, department of medicine, at the University of California, San Francisco, in an email.
GBI Research estimated in a report that the cost of treating rheumatoid arthritis in the United States would climb to $9.3 billion per year in 2020 from $6.4 billion in 2013. At the same time, the number of people with the disease is expected to rise to 1.68 million by 2020.
So, if the device proves to work for just a portion of the broader RA patient population, billions of dollars could be saved by reducing the use of specialty biologic drugs, according to ACR.
The college also is trying to curb an apparent trend by physicians to prescribe biologics for RA more frequently than they should. The college in 2012 updated its treatment guidelines to recommend the use of the cheaper, more established class of rheumatology drugs before turning to the more costly biologics. In 2013, it made a similar recommendation as part of its participation in the Choosing Wisely campaign, which aims to limit unnecessary procedures or treatments.
A different approach
Before any savings can be reaped, researchers have to finish trials to make sure the technology works and is safe. They are not starting from scratch. The broader field of neuromodulation has existed for years, but its application has been limited to procedures in which little is understood about the mechanics, says Christopher Czura, vice president of scientific affairs at Feinstein.
The medical community has known for some time that pain can be relieved by blocking nerve conduction and that stimulating the brain can relieve symptoms of Parkinson’s disease, he says, but the reasons they work have been mostly a mystery. In bioelectronic medicine, a subset of neuromodulation, the why is crucial.
“We bring the pharmaceutical rigor of drug development to the concept of stimulating nerves to treat disease,” Czura says. “We understand the full molecular pathway of why it works.”
The federal government also aims to expand knowledge in neuromodulation. The National Institutes of Health has committed $240 million over six years to encourage different scientific communities to collaborate, focusing first on why an approach might work before asking if it would work.
“The purpose of the NIH program really is to produce a culture change for the neuromodulation community,” says Grace Peng, technology team leader for the program, called Stimulating Peripheral Activity to Relieve Conditions, or SPARC. Peng also is program director for disovery science and technology, National Institute of Biomedical Imaging and Bioengineering. “The field is recognizing now that we need to understand the mechanisms behind why some of these devices work or don’t work. We want to facilitate more successes in clinical trials.”
As both a neurosurgeon and an immunologist, Tracey has a rare combination of skills in the research world and just the type of expertise needed for this research. Getting researchers with different skills to collaborate is a goal of the SPARC program, which is part of a larger push for cooperative research efforts across the National Institutes of Health called the NIH Common Fund.
“We’re hoping to engage a number of communities,” Peng says.
Given the complicated nature of the nervous system, gaining the desired understanding will take time. The vagus nerve, a major area of focus, runs out of the brain and has 80,000 to 100,000 nerve fibers. “The idea going forward will be to have extremely precise, extremely small electrodesthat can stimulate a few nerve fibers at a time,” Tracey says.
SetPoint’s research involves the use of a modified stimulator that originally was designed to treat depression and epilepsy. The epilepsy version of the device pulses for about 30 seconds, every five minutes, 24/7, Czura says.
SetPoint recalibrated the device to run in the rheumatoid arthritis trial for just 30 seconds once a day, and that has shown to be enough to work, he says. In addition to the implantable nerve regulator, the treatment requires a wireless charger and an Apple iPad prescription app. Late last year, the company announced it was launching a similar trial to treat Crohn’s disease, an inflammatory bowel disease.
Will it work?
Like any treatment in the trial phase of development, the experimental SetPoint devices or the approach in general may not prove to be viable. “It’s a long road between here and there,” says Mark Genovese, M.D., James W. Raitt Professor of Medicine and co-chief in the division of immunology and rheumatology, Stanford University School of Medicine.
Using the nervous system to modulate inflammation is a totally new concept, so ensuring that it’s safe and effective for patients might not be straightforward.
“This approach is so unique and novel it’s going to require some degree of replication and additional data to know what it can or can’t do,” Genovese says. “The [trial] data is early. We need to see a lot more of it to feel comfortable about the potential benefits and the risks of this approach.”
Kevin Tracey, M.D., is president of the Feinstein Institute for Medical Research, part of the North Shore-LIJ Health System and one of the few academic-affiliated medical research organizations to operate separately from the teaching side of an academic health system. Tracey, who led research on what could become an electronic cure for such inflammatory diseases as rheumatoid arthritis, argues that research is suffering from a lack of federal support and that the health care system should pick up some of that slack.
What happened with the federal funding?
We have lived through an economic collapse, which changed the way research is supported in the United States. The classic model for supporting biomedical research was focused on National Institutes of Health money going to support molecular medicine research. And what happened was that the economy recovered, but the NIH budget has not.
How drastic is the change for NIH-supported funding?
We’re currently looking at a 20 to 25 percent decrease in our real buying power from 12 to 13 years ago.
What are the consequences?
For whatever reason, the decisions have been made that research is not valuable. That’s exactly the wrong decision, particularly when the upside of research — whether it’s to improve quality of life, life span or value to society, or because it creates jobs and produces new industries — has never been higher. To cut research in a down time is like sending the firemen home because the first floor is no longer on fire, it’s only the second floor. It just doesn’t make any sense.
Why should health systems back medical research?
North Shore-LIJ has stepped up and supported research at a high level. The phrase we like to use here is: “Research is the process of creating the future.” Health systems right now have a very important role in creating the future of health care. To not engage the research side is a mistake. Health systems have an obligation, because it’s the right thing to do and the country needs it.
The Rheumatoid Arthritis Drug Problem
inoos Yazdany, M.D., associate professor in the division of rheumatology, department of medicine at the University of California, San Francisco, led a study regarding Medicare Part D funding of biologic drugs used to treat rheumatoid arthritis, and determined that patients face an annual co-payment of $2,700 per year. She answered some questions about the problem via email.
How big is the issue of RA medicine affordability?
Medicare patients with Part D pharmacy coverage face very high out-of-pockets for biologic drugs. High drug costs are a significant problem because they may limit adherence and put an enormous financial strain on patients.
Would a device that reduces the need for the high-cost drugs have an impact financially? If so, how?
Any new advance, whether a drug or a device, that improves outcomes in RA at lower cost will have a significant impact by reducing the patient out-of-pocket burden.
Why are some of the RA drugs expensive?
There are complex reasons behind high drug costs in RA, including that it is expensive to develop and make biologics, that there are not yet biosimilar versions available, and that Medicare does not have policies to stabilize or reduce costs, such as negotiating drug prices.
Do any of the costs for those drugs compensate physicians or prescription therapy or is the bulk of that cost for the drug only?
In the Medicare Part D program, the cost of the drug is divided so that Medicare and patients pay the bulk of drug costs, while pharmacy insurance plans and manufacturers (through Part D manufacturer discounts) pay a relatively smaller proportion of costs. In Part D, the revenue for drugs does not reach physicians.