This year’s North American Neuromodulation Society (NANS) annual meeting (13–15 January 2022; Orlando, USA) saw 18-month data from SENZA-PDN—a randomised controlled trial (RCT) evaluating the safety and efficacy of high-frequency spinal cord stimulation (SCS) in painful diabetic neuropathy (PDN) patients—disclosed for the first time. Erika Petersen, a board-certified neurosurgeon and professor in the Department of Neurosurgery at the University of Arkansas for Medical Sciences in Little Rock, USA, presented these findings, stating that they build on previously published six- and 12-month data from the study and demonstrate the durability of this novel, paraesthesia-free treatment option for PDN.
Petersen, who is also the principal investigator for the SENZA-PDN trial (Nevro), began by alluding to previously published data from this study, stating that its six-month results were published in JAMA Neurology in April 2021 and its 12-month results were recently published in Diabetes Care. Providing further context on the importance of this study, she noted that existing treatments for the five million-plus Americans currently living with PDN are “relatively underwhelming”—as medications in this space have shown limited efficacy in studies, while low-frequency neurostimulation has demonstrated adequate response rates but lacks long-term durability.
With this in mind—and owing to the fact 10kHz neurostimulation has historically been used to treat other conditions effectively—an RCT was conducted prospectively across 18 US centres to evaluate high-frequency SCS with the Senza system (Nevro) in PDN patients. Petersen reported that 216 patients were enrolled and underwent 1:1 randomisation to receive either conventional medical management (CMM) or 10kHz stimulation plus CMM. She also stated that participants had to have failed two different medications for refractory diabetic neuropathy to be included.
Providing further insight on the study’s design, Petersen told the NANS audience that its primary endpoint was chronic pain reduction, as per visual analogue scale (VAS) scores, but that neurological function and quality of life measures were assessed too. In the SENZA-PDN trial, patients were also offered the option to cross over from one study arm to the other if they did not have a successful response to their assigned treatment at six months—with 77 patients (93% of those eligible) ultimately opting to move from CMM to 10kHz SCS plus CMM at six months due to being non-responders (<50% pain relief). Some 60 of these crossover patients completed the 18-month follow-up, combining with the 84 patients who were originally randomised to the stimulation group to provide a “sizeable cohort” at 18 months, according to Petersen.
Reporting safety outcomes over 18 months, Petersen said there were no explants of the Senza device due to lack of efficacy in this time, but noted five explants were required due to infection, resulting in an infection explant rate of 3.2%—a figure that is comparable to those seen in published literature on SCS in patients without diabetes. “Infection remains the most common adverse event that we see with SCS procedures,” she said, also relaying that there were no stimulation-related neurological deficits at 18 months and three implantable pulse generator (IPG) revisions due to site-related pain.
Moving on to discuss pain reduction in the study, Petersen reported a “dramatic change” on this front, detailing a precipitous decline from baseline in patients in the original stimulation arm, which was maintained at 18 months. “As soon as they have access to spinal cord stimulation, the pain scores in our crossover population drop as well—and they do not drop at a different proportion,” she added. “They drop to exactly where our original stimulation arm drops to.” Petersen stated that, overall, there was an 85% responder rate (>50% pain relief), as well as the average rate of pain relief being 73% and the rate of remission—patients whose VAS pain score was less than three and stayed that way for six months, continuously—being 68%.
Petersen also informed the NANS audience that the number need to treat (NNT) in the SENZA-PDN trial’s stimulation arm was 1.3. This compares favourably to the same measure in pharmacological studies involving PDN patients, which Petersen had earlier stated is between three and eight. “This is certainly an efficacy level that I think is worth considering due to some of the side-effects that we see on medication,” she added.
Petersen also reported that neurological assessments and physical examinations in the study, evaluating changes in categories including reflexes, sensation and motor strength, revealed that 66% of patients experienced improvements in one of these areas at three months. This was maintained at 12 months in 63% of patients, with the majority of these cases pertaining to sensory improvements, Petersen said. “These sensory improvements are a really interesting observation, as this is the first time that a spinal cord stimulator research study has documented that in detail,” she added.
In addition, she stated that comparisons between the two study arms showed there were fewer hospital visits per 100 patients at both six months and 12 months in the stimulation arm, adding that “there is an indication here that this may be a cost-effective way to improve the quality of care for patients with refractory diabetic neuropathy”. Petersen did go on to note, however, that the trial did not have healthcare utilisation as a primary focus—and further, large-scale analysis is required to confirm these early indications.
“In conclusion, this is the largest randomised controlled trial of spinal cord stimulation for painful diabetic neuropathy that has ever been performed,” she claimed. “Our primary endpoint at three months showed safety and efficacy, and what we show today is durability, as it remains safe and effective [at 18 months].” Petersen added that the trial met seven of its eight secondary endpoints too. She closed her presentation by noting that—based on the strength of this ongoing RCT—the Senza system received US Food and Drug Administration (FDA) approval in July 2021, with data now being collected for the study’s 24-month endpoint as well.