Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain.

INTRODUCTION: A novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the accuracy of the stimulation, not possible with any other commercially available SCS systems. The report of objective spinal cord measurements is essential to increase the transparency and reproducibility of SCS therapy. Here, we report a cohort of the EVOKE double-blind randomized controlled trial treated with CL-SCS for 36 months to evaluate the ECAP dose and accuracy that sustained the durability of clinical improvements. METHODS: 41 patients randomized to CL-SCS remained in their treatment allocation and were followed up through 36 months. Objective neurophysiological data, including measures of spinal cord activation, were analyzed. Pain relief was assessed by determining the proportion of patients with ≥50% and ≥80% reduction in overall back and leg pain. RESULTS: The performance of the feedback loop resulted in high-dose accuracy by keeping the elicited ECAP within 4µV of the target ECAP set on the system across all timepoints. Percent time stimulating above the ECAP threshold was >98%, and the ECAP dose was ≥19.3µV. Most patients obtained ≥50% reduction (83%) and ≥80% reduction (59%) in overall back and leg pain with a sustained response observed in the rates between 3-month and 36-month follow-up (p=0.083 and p=0.405, respectively). CONCLUSION: The results suggest that a physiological adherence to supra-ECAP threshold therapy that generates pain inhibition provided by ECAP-controlled CL-SCS leads to durable improvements in pain intensity with no evidence of loss of therapeutic effect through 36-month follow-up.

Current Waveforms in Spinal Cord Stimulation and Their Impact on the Future of Neuromodulation: A Scoping Review.

BACKGROUND: Neuromodulation is a standard and well-accepted treatment for chronic refractory neuropathic pain. There has been progressive innovation in the field over the last decade, particularly in areas of spinal cord stimulation (SCS) and dorsal root ganglion stimulation. Improved outcomes using proprietary waveforms have become customary in the field, leading to an unprecedented expansion of these products and a plethora of options for the management of pain. Although advances in waveform technology have improved our fundamental understanding of neuromodulation, a scoping review describing new energy platforms and their associated clinical effects and outcomes is needed. The authors submit that understanding electrophysiological neuromodulation may be important for clinical decision-making and programming selection for personalized patient care. OBJECTIVE: This review aims to characterize ways differences in mechanism of action and clinical outcomes of current spinal neuromodulation products may affect contemporary clinical decision-making while outlining a possible path for the future SCS. STUDY DESIGN: The study is a scoping review of the literature about newer generation SCS waveforms. MATERIALS AND METHODS: A literature report was performed on PubMed and chapters to include articles on spine neuromodulation mechanism of action and efficacy. RESULTS: A total of 8469 studies were identified, 75 of which were included for the scoping review after keywords defining recent waveform technology were added. CONCLUSIONS: Clinical data suggest that neuromodulation remains a promising tool in the treatment of chronic pain. The evidence for SCS for treating chronic pain seems compelling; however, more long-term and comparative data are needed for a comparison of waveforms when it comes to the etiology of pain. In addition, an exploration into combination waveform therapy and waveform cycling may be paramount for future clinical studies and the development of new technologies.

Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Cost-utility Analysis of Evoke Closed-loop Spinal Cord Stimulation for Chronic Back and Leg Pain.

OBJECTIVES: The effectiveness of Evoke closed-loop spinal cord stimulation (CL-SCS), a novel modality of neurostimulation, has been demonstrated in a randomized controlled trial (RCT). The objective of this cost-utility analysis was to develop a de novo economic model to estimate the cost-effectiveness of Evoke CL-SCS when compared with open-loop SCS (OL-SCS) for the management of chronic back and leg pain. METHODS: A decision tree followed by a Markov model was used to estimate the costs and outcomes of Evoke CL-SCS versus OL-SCS over a 15-year time horizon from the UK National Health Service perspective. A "high-responder" health state was included to reflect improved levels of SCS pain reduction recently reported. Results are expressed as incremental cost per quality-adjusted life year (QALY). Deterministic and probabilistic sensitivity analysis (PSA) was conducted to assess uncertainty in the model inputs. RESULTS: Evoke CL-SCS was estimated to be the dominant treatment strategy at ~5 years postimplant (ie, it generates more QALYs while cost saving compared with OL-SCS). Probabilistic sensitivity analysis showed that Evoke CL-SCS has a 92% likelihood of being cost-effective at a willingness to pay threshold of £20,000/QALY. Results were robust across a wide range of scenario and sensitivity analyses. DISCUSSION: The results indicate a strong economic case for the use of Evoke CL-SCS in the management of chronic back and leg pain with or without prior spinal surgery with dominance observed at ~5 years.

Clinical Longevity of 106,462 Rechargeable and Primary Cell Spinal Cord Stimulators: Real World Study in the Medicare Population.

INTRODUCTION: Spinal cord stimulators (SCS) are available with either primary cell (PC) or rechargeable cell (RC) batteries. Although RC systems are proposed to have a battery longevity upward of nine years, in comparison with four years for PC systems, there are few studies of longevity of SCS in the real world. MATERIALS AND METHODS: This was an observational, nonrandomized, retrospective study of Medicare beneficiaries who received neurostimulator implants in the outpatient hospital. This study used Medicare fee-for-service claims data from 2013 to 2020. The clinical longevity of the implantable pulse generator (IPG), defined as the duration from implant until removal for any reason, was compared between PC and RC devices. Life distribution analysis was used to approximate device lifespan. The secondary analysis separated removals into explant or replacements. The statistics were adjusted for relevant clinical covariates. RESULTS: A total of 25,856 PC and 79,606 RC systems were included in the study. At seven years after implant, 53.8% of PC IPGs and 55.0% of RC IPGs remained in use. The life distribution modeling analysis projected a median lifespan of 8.2 years for PC and 9.0 years for RC devices. The rate of explant was lower for PC devices (19.2%) than for RC devices (22.0%, hazard ratio (HR) = 0.96, p = 0.082), whereas the rate of replacements was higher for PC devices (33.7%) than for RC devices (29.5%, HR = 1.31, p < 0.001). An analysis of the battery type used in device replacements showed an increasing adoption of PC devices over time. CONCLUSIONS: This large, retrospective, real-world analysis of Medicare claims data demonstrated that the clinical longevity of neurostimulator devices is similar for PC and RC batteries. In the past, clinicians may have defaulted to RC devices based on the assumption that they provided extended battery life. Considering this longevity data, clinicians should now consider the choice between PC and RC devices based on other individual factors pertinent to the patient experience and not on purported longevity claims.

Association Between Levels of Functional Disability and Health-Related Quality of Life With Spinal Cord Stimulation for Chronic Pain.

OBJECTIVES: Pain score, functional disability, and health-related quality of life (HRQoL) are core outcome domains for chronic pain clinical trials. Although greater levels of pain reduction have been shown to be linked to larger gains in HRQoL, little is known of the association between HRQoL and disability in the setting of chronic pain. The aims of this study were to 1) investigate the association between functional disability and HRQoL and 2) estimate the utility values associated with levels of functional disability in patients treated with evoked compound action potential (ECAP) spinal cord stimulation (SCS) for chronic pain. MATERIALS AND METHODS: Data on functional disability assessed using the Oswestry Disability Index (ODI) and HRQoL (EQ-5D-5L) were collected from 204 patients with an Evoke ECAP-SCS device and followed up to 12 months. SF-6D utility scores also were retrieved for 134 of these patients. Multivariable linear regression models adjusted for baseline utility values and patient demographics were used to compare differences in utility values across ODI categories. RESULTS: Significant improvements in functional disability and HRQoL were observed at three- and 12-month follow-up after SCS. Patients reporting "minimum disability," "moderate disability," "severe disability," and "crippled" had mean EQ-5D scores of 0.82, 0.73, 0.59, and 0.45, respectively. The mean change in EQ-5D score was 0.007 per unit change in total ODI score. The R2 statistic showed a moderate level association (49%-64% of variance in EQ-5D explained by ODI). CONCLUSION: ECAP-SCS results in significant improvements in functional disability and HRQoL. This study shows that improvement in function of people with chronic pain before and after ECAP-SCS is associated with improvement in HRQoL.

Consensus Guidelines on Interventional Therapies for Knee Pain (STEP Guidelines) from the American Society of Pain and Neuroscience.

Knee pain is second only to the back as the most commonly reported area of pain in the human body. With an overall prevalence of 46.2%, its impact on disability, lost productivity, and cost on healthcare cannot be overlooked. Due to the pervasiveness of knee pain in the general population, there are no shortages of treatment options available for addressing the symptoms. Ranging from physical therapy and pharmacologic agents to interventional pain procedures to surgical options, practitioners have a wide array of options to choose from - unfortunately, there is no consensus on which treatments are "better" and when they should be offered in comparison to others. While it is generally accepted that less invasive treatments should be offered before more invasive ones, there is a lack of agreement on the order in which the less invasive are to be presented. In an effort to standardize the treatment of this extremely prevalent pathology, the authors present an all-encompassing set of guidelines on the treatment of knee pain based on an extensive literature search and data grading for each of the available alternative that will allow practitioners the ability to compare and contrast each option.

Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain: A Secondary Analysis of the Evoke Randomized Clinical Trial.

Importance: Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system. Objective: To determine whether ECAP-controlled, closed-loop SCS is associated with better outcomes compared with fixed-output, open-loop SCS at 24 months following implant. Design, Setting, and Participants: The Evoke study was a double-blind, randomized, controlled, parallel arm clinical trial with 36 months of follow-up. Participants were enrolled from February 2017 to 2018, and the study was conducted at 13 US investigation sites. SCS candidates with chronic, intractable back and leg pain refractory to conservative therapy, who consented, were screened. Key eligibility criteria included overall, back, and leg pain visual analog scale score of 60 mm or more; Oswestry Disability Index score of 41 to 80; stable pain medications; and no previous SCS. Analysis took place from October 2020 to April 2021. Interventions: ECAP-controlled, closed-loop SCS was compared with fixed-output, open-loop SCS. Main Outcomes and Measures: Reported here are the 24-month outcomes of the trial, which include all randomized patients in the primary and safety analyses. The primary outcome was a reduction of 50% or more in overall back and leg pain assessed at 3 and 12 months (previously published). Results: Of 134 randomized patients, 65 (48.5%) were female and the mean (SD) age was 55.2 (10.6) years. At 24 months, significantly more closed-loop than open-loop patients were responders (≥50% reduction) in overall pain (53 of 67 [79.1%] in the closed-loop group; 36 of 67 [53.7%] in the open-loop group; difference, 25.4% [95% CI, 10.0%-40.8%]; P = .001). There was no difference in safety profiles between groups (difference in rate of study-related adverse events: 6.0 [95% CI, -7.8 to 19.7]). Improvements were also observed in health-related quality of life, physical and emotional functioning, and sleep, in parallel with opioid reduction or elimination. Objective neurophysiological measurements substantiated the clinical outcomes and provided evidence of activation of inhibitory pain mechanisms. Conclusions and Relevance: ECAP-controlled, closed-loop SCS, which elicited a more consistent neural response, was associated with sustained superior pain relief at 24 months, consistent with the 3- and 12-month outcomes.

Effect of age on outcomes after allogeneic disc tissue supplementation in patients with chronic discogenic low back pain in the VAST trial.

Aim: To explore the effects of viable allogeneic disc tissue supplementation in younger patients with discogenic chronic low back pain (CLBP). Patients & methods: VAST was a randomized placebo-controlled trial of disc allograft supplementation in 218 patients with discogenic CLBP. We conducted a post hoc analysis of change from baseline to 12 months in Oswestry Disability Index (ODI) and visual analog scale for pain intensity scores stratified by patient age. Results: Patients aged <42 years receiving allograft experienced greater improvement in ODI (p = 0.042) and a higher ODI response rate (≥10-, ≥15- and ≥20-point reductions in ODI) than those receiving saline (p = 0.001, p = 0.002 and p = 0.021, respectively). Conclusion: Young patients with discogenic CLBP may have significant functional improvement following nonsurgical disc allograft supplementation.

The VAST trial evaluated a new treatment for patients with chronic back pain resulting from one or two degenerated spinal discs. The treatment consists of a single injection of disc tissue supplement. A total of 218 adults participated in the study; most received the active treatment, while a smaller number (39 patients) received an injection of saline. In this paper we explain what happened over the 12 months after the injections. Patients who were younger (<42 years old) experienced more functional benefits (i.e., ability to perform daily tasks) after active treatment compared with those who received the saline injection, as measured by disability score. In contrast, older patients (≥42 years old) experienced functional benefits with both active and saline treatments, with no differences between the groups. There were more side effects in both age groups in those who received the active treatment compared with those who received saline, but almost all of the side effects were temporary and not serious. Clinical Trial Registration number: NCT03709901 (ClinicalTrials.gov).

The Cost of Lost Productivity in an Opioid Utilizing Pain Sample.

BACKGROUND AND AIMS: Chronic pain affects more adults in the United States than any other condition. Opioid medications are widely used in the treatment of chronic pain, but there remains considerable risk and cost associated with their use. This study aims to characterize the effects of opioid prescribing for chronic pain and similar pain conditions on lost productivity in the United States. METHODS: This was a retrospective, longitudinal, observational study of chronic pain patients in 2011-2014. We identified patients with a diagnosis of musculoskeletal pain receiving index prescription for opioids in administrative claims and studied disability absence in a linked health and productivity management database. Patients were grouped as de novo and continued use opioid users before index, and by opioid dose in the year after index. Days of disability were compared before and after index with bootstrapping. Effect of opioid dose group on disability was evaluated with negative binomial regression. Lost productivity cost was compared before and after index. RESULTS: The cohort contained 16,273 de novo and 6604 continued use patients. On average, de novo patients used 24.8 days of disability after index, an increase of 18.3 more days compared to before (p < 0.001). Continued use patients used 30.7 days after index, 9 more days than before (p < 0.001). There was a dose-response relationship between dose group and days of disability in de novo patients (p < 0.001). The weighted-average cost per person of lost productivity was $4344 higher in the year after index compared to the year before. CONCLUSION: Opioid prescriptions for pain patients were associated with significant disability use and lost productivity costs. With the evolution of opioid-prescribing practices, CDC recommendations, and the HHS Pain Management Best Practices, there is opportunity to use alternative pain therapies without the risks of opioid-induced side effects to improve work productivity.

Neuromodulation in Treating Pelvic Pain.

PURPOSE OF REVIEW: Chronic pelvic pain (CPP) is a complex condition that can be multifactorial, disabling, and difficult to treat. It is important to understand the various diagnoses and pathways that can be involved and have an understanding of the available treatment options. RECENT FINDINGS: There is a complex innervation of the pelvic region which makes its treatment very challenging. There are pathophysiological similarities of CPP to disease states like complex regional pain syndrome and sympathetically driven pain. CPP is poorly understood and includes psychological, psychosocial, cultural, and economic influences. Treatment options vary, but neuromodulation does remain a centerpiece and can include sacral stimulation, SCS, DRG stimulation, and PNS.

BURST(able): A Retrospective, Multicenter Study Examining the Impact of Spinal Cord Stimulation with Burst on Pain and Opioid Consumption in the Setting of Salvage Treatment and "Upgrade".

BACKGROUND: Loss of efficacy (LOE) is a well-known phenomenon associated with spinal cord stimulation (SCS) and is the leading cause of explant. Although recent advances in neuromodulation have resulted in a decreased incidence of LOE, it still occurs. Intuition suggests that when LOE ensues, switching to a different SCS therapy/platform could potentially be a viable clinical option; however, there are no data presently available to validate this theory. OBJECTIVES: The primary objective was to evaluate the efficacy of SCS therapy rotation with DeRidder Burst on reversing LOE. A subobjective was to evaluate the hypothesis that the body will treat a novel waveform as a "different therapy" when introduced for the first time, regardless of the setting. STUDY DESIGN: Multicenter, retrospective. SETTING: Private practice. METHODS: A total of 307 patients with ongoing SCS therapy had a de novo therapy conversion to DeRidder Burst via surgical revision or software upgrade. Each cohort was split into 2 additional arms/subcohorts: those who were failing their SCS (salvage) versus those who were reporting success with their SCS system but were looking for increased pain relief (upgrade). This study was physician-directed and not commercially funded. RESULTS: There were statistically significant reductions in Numeric Rating Scale, percent pain relief in both surgical revision and software upgrade arms. A statistical reduction in opioid dosing was seen in the overall population and the salvage group. Larger reductions in pain/opioid consumption were observed in the surgically revised group when the revision was performed earlier. Subgroup analysis showed both salvage and upgrade groups restored treatment efficacy irrespective of time or the previous frequency/waveform. LIMITATIONS: The retrospective nature of the study and the inability to eliminate potential confounding variables when evaluating the use of opioids in the study population. CONCLUSIONS: LOE is an unfortunate occurrence with few evidence-based solutions presently available to reverse it. Our findings suggest that implementing D-Burst stimulation may be an effective option for treating LOE, as well as potentially reducing opioid consumption, regardless of the prior SCS system.

A Systematic Literature Review of Peripheral Nerve Stimulation Therapies for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain. DESIGN: Grade the evidence for PNS. METHODS: An international interdisciplinary work group conducted a literature search for PNS. Abstracts were reviewed to select studies for grading. Inclusion/exclusion criteria included prospective randomized controlled trials (RCTs) with meaningful clinical outcomes that were not part of a larger or previously reported group. Excluded studies were retrospective, had less than two months of follow-up, or existed only as abstracts. Full studies were graded by two independent reviewers using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: Peripheral nerve stimulation was studied in 14 RCTs for a variety of painful conditions (headache, shoulder, pelvic, back, extremity, and trunk pain). Moderate to strong evidence supported the use of PNS to treat pain. CONCLUSION: Peripheral nerve stimulation has moderate/strong evidence. Additional prospective trials could further refine appropriate populations and pain diagnoses.

A Systematic Literature Review of Dorsal Root Ganglion Neurostimulation for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain. DESIGN: Grade the evidence for DRG stimulation. METHODS: An international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: DRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies. CONCLUSIONS: Moderate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

A Systematic Literature Review of Spine Neurostimulation Therapies for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of spinal cord stimulation (SCS) for pain. DESIGN: Grade the evidence for SCS. METHODS: An international, interdisciplinary work group conducted literature searches, reviewed abstracts, and selected studies for grading. Inclusion/exclusion criteria included randomized controlled trials (RCTs) of patients with intractable pain of greater than one year's duration. Full studies were graded by two independent reviewers. Excluded studies were retrospective, had small numbers of subjects, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: SCS has Level 1 evidence (strong) for axial back/lumbar radiculopathy or neuralgia (five high-quality RCTs) and complex regional pain syndrome (one high-quality RCT). CONCLUSIONS: High-level evidence supports SCS for treating chronic pain and complex regional pain syndrome. For patients with failed back surgery syndrome, SCS was more effective than reoperation or medical management. New stimulation waveforms and frequencies may provide a greater likelihood of pain relief compared with conventional SCS for patients with axial back pain, with or without radicular pain.

Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial.

BACKGROUND: Spinal cord stimulation has been an established treatment for chronic back and leg pain for more than 50 years; however, outcomes are variable and unpredictable, and objective evidence of the mechanism of action is needed. A novel spinal cord stimulation system provides the first in vivo, real-time, continuous objective measure of spinal cord activation in response to therapy via recorded evoked compound action potentials (ECAPs) in patients during daily use. These ECAPs are also used to optimise programming and deliver closed-loop spinal cord stimulation by adjusting the stimulation current to maintain activation within patients' therapeutic window. We aimed to examine pain relief and the extent of spinal cord activation with ECAP-controlled closed-loop versus fixed-output, open-loop spinal cord stimulation for the treatment of chronic back and leg pain. METHODS: This multicentre, double-blind, parallel-arm, randomised controlled trial was done at 13 specialist clinics, academic centres, and hospitals in the USA. Patients with chronic, intractable pain of the back and legs (Visual Analog Scale [VAS] pain score ≥60 mm; Oswestry Disability Index [ODI] score 41-80) who were refractory to conservative therapy, on stable pain medications, had no previous experience with spinal cord stimulation, and were appropriate candidates for a spinal cord stimulation trial were screened. Eligible patients were randomly assigned (1:1) to receive ECAP-controlled closed-loop spinal cord stimulation (investigational group) or fixed-output, open-loop spinal cord stimulation (control group). The randomisation sequence was computer generated with permuted blocks of size 4 and 6 and stratified by site. Patients, investigators, and site staff were masked to the treatment assignment. The primary outcome was the proportion of patients with a reduction of 50% or more in overall back and leg pain with no increase in pain medications. Non-inferiority (δ=10%) followed by superiority were tested in the intention-to-treat population at 3 months (primary analysis) and 12 months (additional prespecified analysis) after the permanent implant. This study is registered with ClinicalTrials.gov, NCT02924129, and is ongoing. FINDINGS: Between Feb 21, 2017, and Feb 20, 2018, 134 patients were enrolled and randomly assigned (67 to each treatment group). The intention-to-treat analysis comprised 125 patients at 3 months (62 in the closed-loop group and 63 in the open-loop group) and 118 patients at 12 months (59 in the closed-loop group and 59 in the open-loop group). The primary outcome was achieved in a greater proportion of patients in the closed-loop group than in the open-loop group at 3 months (51 [82·3%] of 62 patients vs 38 [60·3%] of 63 patients; difference 21·9%, 95% CI 6·6-37·3; p=0·0052) and at 12 months (49 [83·1%] of 59 patients vs 36 [61·0%] of 59 patients; difference 22·0%, 6·3-37·7; p=0·0060). We observed no differences in safety profiles between the two groups. The most frequently reported study-related adverse events in both groups were lead migration (nine [7%] patients), implantable pulse generator pocket pain (five [4%]), and muscle spasm or cramp (three [2%]). INTERPRETATION: ECAP-controlled closed-loop stimulation provided significantly greater and more clinically meaningful pain relief up to 12 months than open-loop spinal cord stimulation. Greater spinal cord activation seen in the closed-loop group suggests a mechanistic explanation for the superior results, which aligns with the putative mechanism of action for spinal cord stimulation and warrants further investigation. FUNDING: Saluda Medical.