Hello, I'm Chris Gilligan, and today I'm going to be speaking about long-term durability of restorative neurostimulation for chronic mechanical low back pain, and we'll be focusing on two-year pivotal trial results. These are my disclosures. On the left is traditional spinal cord stimulation, typically used to treat neuropathic pain, commonly in the setting of post-laminectomy syndrome, and that obviously is a palliative therapy. It's stimulating sensory fibers, and of course, as you can see on the radiograph at the lower left, the leads are within the spinal canal. Today we're going to be talking about treatment for mechanical nociceptive low back pain, often due to impaired muscle control of the multifidus muscle, the strongest stabilizing muscle of the lumbar spine, and these patients typically have few therapeutic options. Surgery is rarely indicated for many of these patients. This type of stimulation is restorative stimulation. It's stimulating the medial branch nerve in order to overcome inhibition of the multifidus muscle and restore neuromuscular control. The leads, as you can see on the radiograph at the lower right, are outside of the spinal canal. This anatomic drawing shows what the system looks like in place in a patient. Leads are placed at the bilateral L3 transverse processes, such that the contacts are adjacent to the bilateral L2 medial branch nerves. They're then connected to a traditional implanted pulse generator, and the patient is turning this system on for 30 minutes twice a day while laying on their side or prone. Often patients do it in bed before getting up in the morning and before going to sleep in the evening. The rest of the time, the system is off, and again, the idea is to override underlying inhibition of the multifidus. In that way, elicit afferent sensory input as well as restoring neuromuscular control, functional spinal stability, and as a consequence, reducing the patient's pain. This is what the system looks like implanted on an AP and lateral radiograph. And these are the patients who were in our trial. 204 patients implanted at 26 sites around the world, Australia, Europe, UK, and the US. They were relatively young. Their average age was 47. They had 14 years of low back pain on average, and they'd had pain on 97% of the days in the prior year. 100% of our patients had failed physical therapy with an average of 31 sessions. 100% had failed pain medications, and 37% were on opioids at baseline. 52% had failed interventional pain therapies such as radiofrequency ablations. Key exclusion criteria were prior low back surgery or any current indication for low back surgery, and every patient was reviewed by an experienced spine surgeon who looked at their imaging, case report form, et cetera. They couldn't have leg pain greater than back pain. We didn't want patients who had neuropathic pain, and they couldn't have comorbid chronic pain conditions. So if we look at the graphic on the right, we can see where our patients started on average. They had severe pain, 7.3, and their oswestry disability index was 39. That's right where moderate meets severe disability. This is the trial schema. We implanted 204 patients. We randomized them one-to-one to sham stimulation or therapeutic stimulation. We followed that out to the 120-day primary endpoint, and then we crossed over. At that point, we unblinded the patients and crossed the sham stimulation patients over to therapeutic stimulation, and we followed out all of the patients now to one year, two years, and indeed beyond. Today, we're going to focus on the two-year outcomes, which are essentially prospective observational outcomes. We've published elsewhere the results from the 120-day period, and those resulted in FDA approval for the therapy. Here, if we look at the two-year outcomes, patients on average started with a VAS of 7.3. After one year of stimulation, the average was 3.0, and after two years of stimulation, the average was 2.4. For oswestry, they started on average with 39.1. After 12 months, their average was 19, and after two years, their average was 17.6. With the oswestry disability index, anything less than 20 is mild disability. In terms of VAS pain scores, many people will call a patient with 2.5 or less for a low back pain VAS, a low back pain remitter. If we dive into the data a little bit more deeply, and here as we go from light green to dark green, we're looking at pain on the left, disability on the right, so different colors of green for a pain improvement of 30% or more, 50% or more pain, less than 2.5 centimeters, or 70% or greater improvement. What we see is patients improved from baseline to six months. They improved further from six months to 12 months, and they improved further still from 12 months to 24 months, no matter how we slice it in terms of pain. The same holds true with disability, whether we look at oswestry improvement of 10 points or greater, 15 points or greater, 50% or greater, or 20 points or greater. We think this pattern, where the longer we treat the patients, the better they do, is consistent with the restorative nature of this therapy. On this graphic, each yellow dot is an individual patient, and we're looking at the two-year outcomes, and what we're seeing is that 72% of the patients had a 50% or greater improvement in their pain at two years, 64% had a 50% or greater improvement in their oswestry disability index at two years, 77% had a 50% improvement in either their pain or their oswestry disability index, and 59% had a 50% or greater improvement in both their pain and their oswestry disability index. In terms of safety, the two white columns are published averages from Salim Hayek and Sam Aldabi of complication rates for conventional spinal cord stimulation, and the green is what we saw in our trial. We saw a 3% infection rate, we saw 8% implant site discomfort, 3.9% lead fracture or malfunction. Importantly, we saw 0% lead migration. We saw 22% of the patients needing some kind of surgical intervention, 16% it was explant either for needing an MRI, the system isn't yet MRI compatible, although it's undergoing that process right now, or for infection, or in some rare cases for failure to achieve success. 5% of our patients needed a lead replacement. So how can we summarize our two-year outcomes? 72% of the patients had 50% or greater improvement in low back pain, pain. 66% had a pain score of 2.5 centimeters or less at the end of two years. 65% had a 50% or greater improvement in their oswestry disability index. 61% had a 20 point or greater improvement in their oswestry. 77% had a 50% or greater improvement in their pain and or their oswestry disability index. And 59% had a 50% or greater improvement in both their pain and their disability. 80% were definitely satisfied with the treatment. In terms of opioids, 59% of the patients who were on opioids at baseline voluntarily eliminated them, that was 35%, or reduced them, that was 24%. And in terms of safety, we saw a favorable safety profile compared to other implantable neurostimulators. Importantly, we saw no lead migrations. So if we look at the graphic on the right, the red dot is where our patients started on average, and after two years of therapy, they ended with mild pain and mild disability on average. In conclusion, restorative neurostimulation is an effective, durable, and safe treatment for patients with activity-limiting refractory mechanical chronic low back pain. We saw progressive improvements in pain and functional capacity, and we think that those are consistent with the restorative mechanism of action of the therapy. Restorative neurostimulation is complementary to conventional spinal cord stimulation. It targets chronic low back pain patients with predominantly axial nociceptive pain, so it's a different patient population. It employs a restorative or rehabilitative mechanism of action, so it's a different mechanism of action. And we saw a similar treatment size, but it was progressively achieved. Thank you very much for your attention.

restorative neurostimulation

chronic mechanical low back pain

mechanical nociceptive low back pain

medial branch nerve stimulation

pivotal trial results