Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial

Christopher Gilligan,Greg Maislin,Kristiaan Deckers,Willem Volschenk,Ashish Gulve,Ganesan Baranidharan,Frank Huygen,Usman Latif,Richard Rauck,Christopher Gilmore,Jonathan Gentile,Peter Georgius,Eugene Mironer,Antoine Tohmeh,Marc Russo,Jan Pieter Heemels,Meredith Langhorst,Sam Eldabe,Farshad Ahadian,Matthew Green,Vivek Mehta,Edgar L Ross ,Salim M Hayek ,Vikas Patel ,K De Smedt ,Timothy R Deer ,Shivanand P Lad ,Alexios G Carayannopoulos ,James P Rathmell ,William R Klemme ,Jeffrey S Fischgrund ,Jean‐Pierre Van Buyten ,B Mitchell

doi:10.1016/j.neurom.2021.10.011

Abstract

BackgroundImpaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. ObjectiveThis study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. Materials and MethodsOpen-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. ResultsAt two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. ConclusionsAt two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. Clinical Trial RegistrationThe study is registered on clinicaltrials.gov with identifier NCT02577354.

Highlights

Most cases of acute low back pain resolve spontaneously without treatment, but for chronic low back pain (CLBP), the prognosis is not favorable.[1]
At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI
At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction

Summary

Introduction

Most cases of acute low back pain resolve spontaneously without treatment, but for chronic low back pain (CLBP), the prognosis is not favorable.[1]. The multifidus muscles are the most important stabilizers of the lumbar spine and play a crucial role in providing segmental stability in response to changes in posture and protection against sudden perturbations.[8,9,10] Mechanical CLBP is often associated with impaired neuromuscular control and degeneration of the lumbar multifidus muscles.[9,11,12,13] Persistent back pain–induced inhibition and disruption of proprioceptive signaling have been linked to long-term motor cortex reorganization.[14] Results of motor control exercise programs targeting the multifidus muscle are mixed.[15,16] The isolated muscle contractions required to reverse impaired neuromuscular control are difficult to achieve voluntarily, especially in the presence of underlying inhibition and degeneration of the multifidus muscle.[17,18] To overcome these limitations to rehabilitation, a restorative neurostimulation system (ReActiv[8], Mainstay Medical, Dublin, Ireland) was developed to electrically stimulate the medial branch of the L2 dorsal ramus nerve to elicit isolated multifidus muscle activation.[19,20]. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward

Methods

Results

Discussion

Conclusion