PDT for Migraine Improves Patient Outcomes With Potential Cost Savings

In this interview with First Report Managed Care, Alit Stark-Inbar, PhD, and Alon Ironi offer insight into a recent analysis which demonstrated preventive migraine treatment with a prescription digital therapeutic (PDT) was associated with significant cost savings from a US payer perspective.

Can you please provide some background on this prescription wearable device for patients with migraine? How does it work?

Mr Ironi: The Nerivio is a prescribed and self-administered wearable device indicated for the acute and/or preventive treatment of migraine for patients 12 years and older. 

The mechanism of action is based on using external stimulus to trigger central pain inhibition mechanisms in the brain. One of the most important mechanisms for modulating pain is an endogenous mechanism called CPM, or condition pain modulation, and is located in the brainstem. This mechanism processes nociceptive (painful) messages coming from different receptors in the body to quickly make a decision whether they are dangerous and require some sort of action, like fight or flight. If no action is needed, the mechanism can actually abort the pain by releasing neurotransmitters, specifically norepinephrine and serotonin, directly into the nociceptive pathways, from two different locations, one of them is called the trigeminal cervical complex, which is exactly where the migraine develops.

About 15 years ago, researchers found that some people have a deficiency in this mechanism. It fails to trigger when it should. Researchers found a very strong correlation between that kind of deficiency and the prevalence of certain neurological disorders, including migraine. On the other hand, other researchers found that under certain conditions, this mechanism can be triggered using an external stimulus. At Theranica, we combined the two pieces. We engineered a certain electrical waveform to activate the nociceptive receptors of nerve fibers, specifically in the extremities, in the limbs, under the skin. As the device applies this waveform, the nociceptive message is created. It travels all the way to the brainstem where it is processed, and then, in most cases, it manages to trigger that mechanism of action, the CPM.

The device is operated by smartphone application. You place the device on your arm and then hit the start treatment button on the application, and it activates for 45 minutes, during which you can continue with your daily routine. You do not have to use the phone during the treatment.

The device has 2 indications: one for preventive treatment of migraine and one for acute, abortive treatment. 

For abortive treatment, patients use the device whenever they feel the symptoms of a migraine attack. 

For preventive treatment, it is the same procedure, but the modality is not to wait for the symptoms but use the device every other day. 

Thank you for providing that background. What led you to conduct your recent analysis?

Dr Stark-Inbar: There are two reasons that led us to conduct this analysis. Nerivio was initially indicated for acute treatment, and we wanted to expand that indication for preventive treatment as well. For that purpose, we conducted a double-blind, randomized, placebo-controlled clinical trial, collecting prospective data from patients. We found there was a reduction of 4 migraine days on average after 2 months of treatment with Nerivio, vs a reduction of 1.3 days with placebo. That was the clinical evidence we took to the US Food and Drug Administration, which led to the expanded indication to prevention. That was one aspect of it—we wanted to have this clinical data. 

The other reason is more specific. The device has been in the US market for about 4 years. We see there is a strong demand from patients and providers to use the device, but there is also a demand to have its covered. This is a medical device, it costs money, and just like any other treatment, patients want to have it covered by their insurance. We have been working with payers in the last couple of years, and on top of the important data regarding efficacy, safety, and tolerability, we know there is also the financial aspect that is considered by payors.

That is what led us to conduct a health economics study. This study was planned when we planned the clinical trial for migraine prevention. We included exploratory outcomes that would be measured within the trial. Everything in the current analysis is an endpoint that was measured within the trial. To each endpoint we attached a cost per unit, according to the average market cost. This allowed us to first calculate the clinical evidence—the reduction or the improvement—and then how much it costs per patient per month (PPPM), as well as how much it will cost altogether for coverage. 

We extrapolated that for annual savings and for a hypothetical, but very realistic, payer plan that covers 1 million members., which is also easy to multiply and extrapolate to larger plans. Each outcome to which we could have attached cost to, was included in this analysis, and the target was to show how much money payers can save by covering the device.

We looked at direct costs, including health care resource utilization such as acute medication use and appointments. If we are treating for prevention, that means we reduce the number of migraine days per month, so patients have fewer migraine attacks and therefore require fewer abortive medications. How much money we can save by reducing the number of acute medications and clinical appointments with providers? These were the direct outcomes.

We also looked at indirect outcomes, which are important for both patients and payers, especially large payers that work with large employers. We looked at absenteeism, or days in which the patient could not attend work due to their migraine, and presenteeism, or days in which the patient reported having moderate-to-severe functional disability due to their migraine but was not absent from work.

What are the main findings from your research? Did any outcomes surprise you?

Dr Stark-Inbar: Compared to baseline, after 2 months of treatment of Nerivio, we saw a reduction in 3.5 acute medication days PPPM (3.5 ± 0.4 vs. 1.2 ± 0.5; P = .001). The average cost of branded medications for acute migraine treatment in the US market is around $120, so mean annual cost savings from acute medications is nearly $5500 per patient. We also saw a reduction in provider visits of nearly 0.1 day per month (reduction of 0.09 ± 0.1 vs. increase of 0.08 ± 0.2; P = .297). You do not visit your provider every day, so this is a scarce event. But taking the average unit cost, we saw annual cost savings of $380 for provider visits. 

Also, we saw a reduction of 2.7 days of presenteeism PPPM (2.7 ± 0.3 vs. 1.1 ± 0.4; P = .001) and 0.07 days of absenteeism PPPM (0.07 ± 0.1 vs. 0.07 ± 0.2; P = .997). 

If we multiply these by their average unit cost, we reach an annual cost savings of $10,000, for just these four outcomes. 

Within a health plan that covers 1 million lives, about 5.6% of patients within a plan are eligible for migraine prevention, based on the global prevalence of migraine of 14% and 40% of them who are eligible for migraine prevention . By multiplying the PPPM cost savings over a year, we found a reduction of $560 million (±$99.5 million) in annual cost savings, of which $328 million was from direct costs and $232 million from indirect costs. This did not surprise us; it was actually something we expected.

We saw significant cost savings for presenteeism. Presenteeism is a major issue not only for payers, but also for patients and their employers. 

Additional endpoints measured in the clinical trial, such as emergency room visits or inpatient hospital stays, were so rare that we could not find meaningful outcomes. For that, we need a longer study.

How can these findings inform migraine management from a US payer perspective?

Mr Ironi: If you look at the different sources for cost savings, one fact that stands out is the device saves in both medical and pharmacy benefits. When payers first encounter a device like this, they think it will save money on the pharmacy benefit, but may not make the connection to the medical benefit. One of the important things about this study is that it brings up the amount of money that can be saved in direct medical benefits, such as physician appointments, in addition to pharmacy benefits. Overall, for a plan that has both medical and pharmacy benefits, this device presents significant cost savings for both classes of benefits.

Migraine is very prevalent and extremely debilitating. It is not a life-threatening disease but is chronic and noncurable. Typically, patients suffer with migraine for decades. Migraine symptoms often start at early teenage years, especially in women. Then patients must live with migraine through their early mid-60s. 

Translating that into the economic burden, this represents an amazing amount of money over the membership lifespan of a patient. The amount of money the health plan ends up paying because of migraine, including preventive drugs, abortive drugs, physician appointments, ER visits, etc, is really large. So, it is beneficial to significantly reduce those costs with a device that is also safe, efficacious, and simple to use. 

Dr Stark-Inbar: In this analysis, the findings are connected to endpoints that we measured during our clinical trial, so the cost savings that we show here are actually conservative. They do not take into account the cost of the device, or the cost per treatment, as compared to other preventive treatments. When accounting also for treatment costs, that will add a lot more savings. 

Do you intend to expand on your research in the future?

Dr Stark-Inbar:  We have 17 papers out there, of which 16 report the efficacy, safety, and tolerability of the device. This analysis is our first paper about health economics. Payers already have evidence regarding the safety and efficacy, but there is still more need to show the cost saving aspect. 

For that, we are working with a few payers in the United States, conducting commercial studies that are health economics-oriented, to show outcomes like those we showed here, plus also look at claims. These coverage with evidence studies will allow us to show what the payer spends across a larger duration of time, from before they started covering Nerivio during the study, to when they have covered it for a long period of time. That gives us a longer term to compare savings with real-world data from payers. We are happy to expand that and would like to conduct more studies like that.

Is there anything we have not touched on yet that you would like to add?

Mr Ironi: Migraine, as a disease, historically has been treated by pharmacological medications. For a lot of people, including some providers and payers, it is difficult to shift toward prescribing or covering a non-pharmacological solution. Going back to your question on what drove us to conduct this study, this is exactly why: to generate evidence that the paradigm shift from only pharmacological therapies to including nonpharmacological therapies may be valuable economically, on top of providing clinical benefits.

Also, you can never assess or evaluate all the pharmacological therapies together because they are very different from each other in their mechanisms of action and usage. In the same way, one of the educational challenges that we face is to explain that not all nonpharmacological solutions or devices are the same. There are several devices on the market, and you cannot accept or rule them out altogether. You must look at the clinical and health economic data of each and every one.

Over a relatively short period of time, we managed to generate a large number of studies, some of them including thousands of participants. Payers also want to real-world evidence. The current analysis is like real-world evidence, but not exactly. The work Dr Stark-Inbar has mentioned that we are doing together with payers is a complete, 100% simulation of real life. This kind of evidence is important to solidify the role that nonpharmacological therapies can play in migraine and in other pain-related diseases.

Dr Stark-Inbar:  Nerivio is indicated for the acute and/or preventive treatment of people with migraine, with or without aura, for people aged 12 and older. That means we are providing a solution to adults, as well as for adolescents, for whom the need is even stronger because of the lack of medications that are approved for that age group. For all people living with migraine, and especially for this age group, Nerivio is a relevant treatment option.

About Mr Ironi

Alon Ironi is cofounder and chief executive officer of Theranica. Mr Ironi is a hi-tech entrepreneur and executive with over 30 years of experience across algorithm, hardware, and real-time software development, and executive management of start-up companies in the areas of digital communications and medical devices.

Combining deep technical expertise—as an electronics engineer educated in the Technion, Israel, and in Santa Clara University, California—with strong creative design capabilities, Mr Ironi is the inventor of several patents in electronics and medical devices, and the coauthor of 15 scientific peer-reviewed papers. 

About Dr Stark-Inbar

Alit Stark-Inbar, PhD, is a multidisciplinary NeuroTech executive connecting science, technology and clinical needs to translate scientific advancements into innovative health solutions with the aim of improving the lives of individuals with neurological disorders/diseases.

As vice president of medical information at Theranica, Dr Stark-Inbar leads clinical studies and real-world evidence research on the efficacy, safety, tolerability, and health economics of Nerivio, the drug-free, smartphone controlled, wearable device for the treatment of migraine.

Dr Stark-Inbar received a doctorate in neuroscience from the Hebrew University and conducted postdoctoral training at the University of California, Berkeley, after which she held multiple leadership positions in NeuroTech companies in the United States and Israel.