Spinal cord stimulation (SCS) with a closed-loop system that uses recorded evoked compound action potentials (ECAPs) is superior to a fixed-output, open-loop system for patients with chronic back and leg pain, according to study results published in Lancet Neurology.
While SCS has been a well-established treatment for chronic pain for more than 50 years, the results are suboptimal. The major challenge in SCS is the changing distance between the stimulating electrodes and their spinal cord target, because while the spinal cord changes position within the cerebrospinal fluid with every movement, the electrode is fixed in the epidural space.
The available SCS systems are open-loop systems and do not measure or adjust for changes in the electrical field strength reaching the spinal cord, leading to unpredictable inhibition of pain-processing pathways. An ECAP-controlled, closed-loop system can change the stimulation output current as needed.
The goal of the current double-blind, randomized-controlled study was to compare the safety and efficacy of ECAP-controlled, closed loop SCS with that of fixed-output, open-loop SCS for patients with chronic back and leg pain.
The study included patients with chronic intractable pain of the back and legs who were refractory to conservative therapy and on stable medications. The participants were randomly assigned to receive ECAP-controlled closed-loop SCS or fixed-output, open-loop SCS.
The primary objective was to show noninferiority, and then to test the superiority, of closed-loop SCS compared with open-loop SCS. The primary outcome, tested at 3 and 12 months after the permanent implant, was a composite outcome that included the proportion of patients who responded to SCS with a ≥50% reduction in overall back and leg pain as determined by visual analog scale score, with no increase in analgesics.
The study enrolled 134 participants: 67 were assigned to closed-loop (investigational) group and 67 to open-loop (control) group.
In the intent-to-treat population, the percentage of responders with ≥50% reduction in overall back and leg pain and no increase in pain medications at 3 months was 82.3% (51 of 62 patients) in the closed-loop group vs 60.3% (38 of 63 patients) in the open-loop group. At 12 months the response rates were 83.1% (49 of 59 patients) and 61.0% (36 of 59 patients), respectively. Noninferiority was demonstrated at 3 months (P <.0001) and 12 months (P <.0001), as was superiority (3 months, P =.0052; 12 months, P =.0060).
The type, nature, and severity of adverse events were similar between treatment groups. There were 23 adverse events in 13 patients (19%) in the closed-loop group and 11 adverse events in 11 patients (16%) in the open-loop group. The most common study-related adverse events were lead migration, implantable pulse generator pocket pain and muscle spasm or cramps.
Lawrence Poree, MD, MPH, PhD, Director of Neuromodulation Service, Division of Pain Medicine at University of California, San Francisco and the senior author of the study commented that “these are impressive clinical outcomes for comprehensively managing patients’ pain effectively over the long term. The more than 50 percent of closed-loop patients who reached high responder status of greater than or equal to 80% reduction in overall pain also demonstrated clinically meaningful changes in secondary patient-reported outcomes, emphasizing the value of achieving this high threshold.”
“Closed-loop spinal cord stimulation provided greater levels of spinal cord activation, within the therapeutic window, which suggests a mechanistic explanation for the superior results. Although preliminary, we believe this is the first step in the field of neuromodulation, moving towards a mechanism-based, personalised therapy founded on an objective outcome measure,” concluded the researchers.
Disclosure: This clinical trial was supported by Saluda Medical. Please see the original reference for a full list of authors’ disclosures.
Mekhail N, Levy RM, Deer TR, et al. 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 [published online ahead of print, 2019 Dec 20]. Lancet Neurol. 2019;S1474-4422(19)30414-4. doi:10.1016/S1474-4422(19)30414-4
This is part 1 of a 2 part feature. In part 2 Neurology Advisor interviews Nagy Mekhail, MD, PhD, Professor at the Cleveland Clinic Lerner College of Medicine, Director of Evidence-Based Pain Medicine Research and Education in the Department of Pain Management at the Cleveland Clinic, and first author of this study.