EVOKE™ Therapy for Painful Diabetic Neuropathy: A Subgroup Analysis of the ECAP Study

Introduction: Diabetes mellitus (DM) is a common long-term condition that affects 9.3% of the world’s population.1 Approximately a quarter of these patients will develop painful diabetic neuropathy (PDN).2 Available treatments for the management of PDN are often ineffective and/or cause adverse effects.3 Fixed-output SCS for PDN has shown improvements in pain intensity and health-related quality of life.4-7 EVOKE™ Therapy through ECAP-controlled closed-loop SCS has demonstrated incremental benefits over fixed-output SCS for chronic refractory back and leg pain up to 36-months follow-up,8-10 though efficacy for PDN is unknown. The current study presents the first evaluation of EVOKE Therapy for PDN and for the first time presents holistic treatment response and the neural dosing parameters that produced the treatment effect in a population with PDN.

Methods: The ECAP Study was a prospective, multicenter, single-arm study conducted at 22 sites throughout the United States to collect routine clinical care data while applying a rigorous data collection approach consistent with RCT methodology.11 The current subgroup analysis comprises of adult patients with diagnosis of DM type 1 or 2, with refractory PDN of the lower limbs defined as VAS≥50 and DN4-interview≥3.12,13 Holistic treatment response was assessed using validated methods previously described14,15 including seven domains from the PROMIS-29 questionnaire. Minimal clinically important differences (MCIDs) were used to characterize response to EVOKE Therapy at maximal analgesic effect post-implant visit. EVOKE Therapy, characterized by objective neurophysiologic measurements from the spinal cord in response to ECAP-controlled closed-loop stimulation, provided information on system utilization, closed-loop performance, and neurophysiologic dose metrics.

Results: Thirty-five patients with PDN received EVOKE Therapy following a temporary trial phase. A mean ≥2 MCIDs were obtained for six of the seven domains at post-implant visit (Figure 1). The cumulative responder score which reflects the total number of MCIDs obtained across PROMIS-29 domains was 13.5±6.9. The Holistic MCID which adjusts the cumulative responder score by the number of impaired baseline domains was 2.5±1.2. Most patients (94%) were considered holistic MCID responders, i.e., obtained ≥1 holistic MCID. EVOKE Therapy consisted of system utilization of 88% with stimulation at or above the individual’s ECAP threshold 99% of the time, median dose ratio of 1.4 which translates to an ECAP dose of 33.8μV, and neural dose accuracy of 2.4μV (Table 1).

Conclusion: EVOKE Therapy can provide profound clinical benefits for patients with PDN. Physiologic therapy metrics show consistent neural activation for the PDN population in line with previous reports of closed-loop SCS.16