Combination therapy with simultaneous delivery of spinal cord stimulation modalities: COMBO randomized controlled trial.

Aim: The Combining Mechanisms for Better Outcomes randomized controlled trial assessed the effectiveness of various spinal cord stimulation (SCS) modalities for chronic pain. Specifically, combination therapy (simultaneous use of customized sub-perception field and paresthesia-based SCS) versus monotherapy (paresthesia-based SCS) was evaluated. Methods: Participants were prospectively enrolled (key inclusion criterion: chronic pain for ≥6 months). Primary end point was the proportion with ≥50% pain reduction without increased opioids at the 3 month follow-up. Patients were followed for 2 years. Results: The primary end point was met (n = 89; p < 0.0001) in 88% of patients in the combination-therapy arm (n = 36/41) and 71% in the monotherapy arm (n = 34/48). Responder rates at 1 and 2 years (with available SCS modalities) were 84% and 85%, respectively. Sustained functional outcomes improvement was observed out to 2 years. Conclusion: SCS-based combination therapy can improve outcomes in patients with chronic pain. Clinical Trial Registration: NCT03689920 (ClinicalTrials.gov), Combining Mechanisms for Better Outcomes (COMBO).

Spinal cord stimulation (SCS) is a device-based therapy for chronic pain that delivers electrical impulses to the spinal cord, disrupting pain signals to the brain. Pain relief can be achieved using different SCS techniques that use or do not use paresthesia (stimulation that produces a tingling sensation). These approaches affect patients in different ways, suggesting that different biological processes are involved in enabling pain relief. Research also suggests that better long-term results occur when patients can choose the therapy that is best for their own needs. This clinical study compared pain relief and other functional activities in those receiving combination therapy (simultaneous use of SCS that does and does not produce tingling sensation) against those receiving monotherapy (only SCS therapy producing tingling sensation) for 3 months. In the study, 88% of those receiving combination therapy and 71% with monotherapy alone reported a 50% (or greater) decrease in overall pain (the 'responder rate') without an increased dose of opioid drugs at 3 months after the start of therapy. This responder rate was found to be 84% at 1 year and 85% at 2 years (with all SCS therapy options available). Analysis of functional activities or disability showed that patients improved from 'severely disabled' at study start to 'moderately disabled' after 2 years, indicating that effective long-term (2 year) improvement can be achieved using SCS-based combination therapy for chronic pain.

Long-term safety of spinal cord stimulation systems in a prospective, global registry of patients with chronic pain.

Aim: The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Methods: Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Results: Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). Conclusion: This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. Clinical Trial Registration: NCT01719055 (ClinicalTrials.gov).