The Ohio Society of Interventional Pain Physicians supports the use of Senza®, Senza II™ and Senza Omnia™ Spinal Cord Stimulation (SCS) systems for diabetic neuropathy in patients refractory to conventional therapy.
Diabetic peripheral neuropathy is a common complication of diabetes presenting as pain and other dysesthesias, including numbness, burning, or tingling. Approximately 20% of patients with diabetes will develop painful diabetic neuropathy (PDN), a progressive, potentially debilitating chronic neuropathic pain condition which is described as burning, tingling, shooting, sharp and lancinating pain, initially starting in both feet, with the potential to progress up to the legs (often to the knees) and to the hands over time.1,2,3
Current PDN treatments include medications such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, opioids, and topical solutions. Randomized clinical trials demonstrate limited efficacy of these medications with high incidence of adverse effects with a majority of patients discontinuing medications by 6 months.1,6,7
The clinical burden of diabetic neuropathy is well-documented, and studies have demonstrated increased morbidity and mortality related to ulcers, infections, amputations, pain management, and poor adherence to therapy. Compared to the general population, individuals with diabetic neuropathy are at an increased risk of chronic pain, foot ulcerations, foot infections, and amputations. A retrospective claims analysis over a five-year time horizon found amputation risk in the PDN subgroup was 16.24 times that of diabetic controls.4
In addition to the clinical burden, PDN is associated with considerable direct and indirect economic costs and high healthcare resource utilization.4,5 In a retrospective claims analysis of healthcare utilization costs of patients with diabetes, direct medical costs were 4 times higher for patients with PDN vs patients with diabetes alone, $31,211 vs $7,875, respectively.4
There is an unmet need for this patient population and Ohio Society of Interventional Pain Physicians support the use of the Senza® SCS systems as the only non-pharmacologic option, with a specific FDA-approved indication, for the treatment of pain associated with diabetic neuropathy in patients refractory to conventional therapy.
FDA Indication and Labeling
The Senza®, Senza II™, and Senza Omnia™ Spinal Cord Stimulation (SCS) Systems are indicated as an aid in the management of chronic intractable pain of the trunk and/or limbs, including unilateral or bilateral pain associated with the following: failed back surgery syndrome, intractable low back pain, and leg pain. Additionally, all Senza systems are indicated as aids in the management of chronic intractable pain of the lower limbs, including unilateral and bilateral pain associated with diabetic neuropathy.
The Senza system received CE mark in 2010, TGA approval in 2011, FDA PMA approval in 2015, and is commercially available in Europe, Australia, and the United States. In the U.S., Nevro’s Senza SCS systems are approved to deliver both traditional SCS low frequencies of 2 – 1,200 Hz and are the only systems approved to deliver 10,000 Hz frequencies. This combination of therapies offers the most waveform types in a single product, helping patients to achieve long-term pain relief.
Therapy Description
The Nevro SCS device portfolio includes Senza, Senza II, and Senza Omnia devices and are all minimally invasive, reversible, and typically prescribed for the treatment of pain of the back, trunk, and/or limbs. Stimulation at 10 kHz is unique to HFX™ and is indicated as paresthesia-independent therapy to provide pain relief without inducing paresthesias, a buzzing or tingling sensation common in lower frequency stimulation. This is especially well-matched for patients with PDN whose pain can already present with uncomfortable paresthesias.
Clinical Evidence
The SENZA-RCT was the first multicenter, prospective, randomized, controlled pivotal study of an SCS system with 24-month follow-up across 11 US pain centers comparing long-term results of 10 kHz therapy vs traditional low-frequency SCS. At both 12 and 24-month endpoints subjects in the 10 kHz study arm achieved statistically significant pain reduction and demonstrated long-term superiority of 10 kHz therapy compared with traditional SCS in both back and leg pain. Results of both the 12 and 24-month endpoints were published in the peer-reviewed scientific journals of Anesthesiology and Neurosurgery, respectively.8,9
The same mechanism of action demonstrated to be superior to traditional SCS in the SENZA-RCT is used to treat PDN. Rather than stimulating the dorsal column and creating paresthesias to mask the pain, 10 kHz SCS directly targets inhibitory pain-circuit neurons in the dorsal horn, providing pain relief without paresthesia.10
Painful Diabetic Neuropathy
On July 16, 2021, Nevro became the first and only company to receive FDA approval for an expanded indication for its Senza Spinal Cord Stimulation systems to treat patients with pain of the lower limbs associated with diabetic neuropathy.
The FDA approval was based on an expansive body of clinical evidence including the largest RCT ever conducted for SCS in PDN patients showing the following results11:
85% of patients treated with 10 kHz Therapy achieved meaningful pain relief (as defined by 50% or more pain relief) vs only 5% of patients treated with conventional medical management (CMM).
76% average pain relief for 10 kHz Therapy patients vs -2% for patients with CMM alone.
62% of 10 kHz Therapy patients reported neurological response such as reduced burning, numbness, tingling and cold sensation vs 3% for patients with CMM alone.
2.2% Explant Rate at 6-months with both explants due to infection and none due to loss of efficacy
References
1. Pop-Busui R, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-154.
2. Gore M, et al. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30(4):374-385.
3. Schmader KE. Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clin J Pain. 2002;18(6):350-354.
4. Kiyani M, et al. Painful diabetic peripheral neuropathy: health care costs and complications from 2010 to 2015. Neurol Clin Pract. 2020 Feb;10(1):47-57.
5. Sadosky A, Schaefer C, Mann R, et al. Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey. Diabetes Metab Syndr Obes. 2013;6:79-92.
6. Gabapentin and risk of severe respiratory depression. Drug Ther Bull. 2018;56(1):3-4 doi: 10.1136/dtb.2018.1.0571
7. YangM, et al. Suboptimal treatment of diabetic peripheral neuropathic pain in the United States. Pain Med. 2015;16(11):2075-2083. doi:10.1111/pme.12845
8. Kapural L, et al. Novel 10-kHz high-frequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: The SENZA-RCT randomized controlled trial. Anesthesiology. 2015 Oct;123(4):851-60. doi: 0.1097/ALN.0000000000000774.
9. Kapural L, et al. Comparison of 10-kHz high-frequency and traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: 24-month results from a multicenter, randomized, controlled pivotal trial. Neurosurgery. 2016 Nov;79(5):667-677. doi: 10.1227/NEU.0000000000001418.
10. Lee, K, et al. Low-intensity, kilohertz frequency spinal cord stimulation differently affects excitatory and inhibitory neurons in the rodent superficial dorsal horn. Neuroscience. 2020, 132-139. doi.org/10.1016/j.neuroscience.2019.12.031.
11. Petersen, E, et al. Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy A Randomized Clinical Trial. JAMA Neurology, April 2021.