ReActiv8’s clinically important disability, pain and quality-of-life improvements sustained at one-year

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The disruption of lumbar multifidus muscle control is one factor involved in many cases of functional instability and chronic low back pain. Whilst targeted movements can improve control of the muscle, a large number of patients cannot perform these kinds of exercise. Mainstay Medical—a company based in Dublin, Ireland—have developed a device designed to stimulate the lumbar multifidus muscle electronically. At one year, trial results presented at the North American Neuromodulation Society annual meeting (NANS; 19–22 January 2017, Las Vegas, USA) have shown positive safety and efficacy results for the device.

ReActiv8 is currently being investigated by two studies; the ReActiv8-A and ReActiv8-B trials. ReActiv8-A is an international, multicentre, prospective, single-arm trial collecting data on safety and efficacy. Interim trial results were presented at NANS. The ReActiv8-B trial—which enrolled its first patient in September 2016—is investigating the device for pre-market US Food and Drug Administration approval.

ReActiv8-A included individuals with disabling chronic back pain in spite of physical and drug therapy who had not had previous spinal surgery, and who had greater back pain than leg pain. On average, participants had experienced back pain for 14 years. Seventy per cent of subjects were receiving opioid therapy. Following implantation of the ReActiv8 device, patients self-administered twice-daily, 20-minute stimulation sessions via remote control.

Participants were followed from baseline (n=53) to one year (n=47), and assessed for improvements in low back pain, disability and quality of life. At baseline, mean low back pain measured 6.8±1.2 on the Numerical Rating Scale, average disability was reported as 44.5±10.5 on the Oswestry Disability Index, and mean quality of life was recorded at 0.434±0.185 on the EuroQol five dimensions questionnaire.

Clinically important improvements from baseline in all three measures were recorded in the almost half of subjects at 90 days (40%, n=52), six months (45%, n=51), and at one year (47%, n=47). The vast majority of patients improved in at least one of the three areas at each timepoint (94% at 90 days, 86% at six months and 87% at one year). Patient satisfaction, too, was remarkably high at one year. The majority of patients (73% at 90 days, 73% at six months and 60% and one year) were “very satisfied” with the treatment, alongside 15%, 12% and 21%, respectively, who reported that they were “satisfied” at each timepoint.

Investigator Sam Edalbe (Middlesbrough, UK)—who presented the data at NANS—concluded that this new treatment resulted in a statistically significant, clinically important and lasting improvement in the three areas studied. The device was granted CE mark last year based on the successful ReActiv8-A data, with the first implantation taking place in Germany in January of this year.

Mainstay Medical’s ReActiv8

Spinal News International spoke to ReActiv8-A investigator, Kris De Smedt (Antwerp, Belgium), about his work with the technology.

What kinds of patients could benefit from this treatment?

Chronic low back pain (CLBP) without an identifiable anatomical cause is a very common condition in our spine surgery practice. An underappreciated but common cause of CLBP is the loss of lumbar stabilisation due to arthrogenic inhibition of the multifidus muscle after an acute injury of one of the joints or discs. In most cases this inhibition spontaneously resolves within weeks as the initial injury heals. However, if it persists, it can result in a self-sustained predominantly nociceptive chronic pain state.

A magnetic resonance imaging (MRI) test in these patients typically shows no structural defects that can be resolved by surgery, but often reveals fat infiltration and atrophy of the multifidus.

Please could you briefly describe the concept behind the ReActiv8 technology?

Several studies have demonstrated that these patients have a good chance of recovering if these muscles are succesfully reactivated.

To override the arthrogenic inhibition, ReActiv8 delivers electrical stimulation to the motor neurons in the L2 dorsal ramus to elicit episodic contraction of the lumbar multifidus muscles. This facilitates restoration of motor control in a similar fashion that stimulated contractions of the quadriceps help patients regain voluntary control after knee surgery.

Because ReActiv8 treats the cause (motor control) rather than the symptom (pain), it is referred to as a restorative neurostimulator.

The patients in the ReActiv8-A trial have had back pain for upwards of a decade on average, and have not responded to drug treatments. What other options do such patients have for pain relief?

At this stage of the disease, the options for these patients become very limited. After receiving state-of-the-art conservative therapy over a long period of time, they often come to our practice to inquire about surgical options. However, for these patients, surgery is typically not an alternative.

Almost half of patients experienced improvement in all three areas of pain, disability and quality of life at one year. Were you expecting the results to be so strong?

When we got involved in the feasibility study in 2012, we had no idea what to expect from the therapy, but what intrigued and interested us was the holistic functional treatment of the lumbar spine, as opposed to surgery which focuses on one anatomical issue.

Patient satisfaction was very high (81% “satisfied” or “very satisfied” at one year). How does this compare for other kinds of treatment for low back pain?

These patients have no anatomical indications for surgery and are refractory to all available non-surgical treatments, including physical therapy and drugs prescribed to them over their many years of suffering. A direct comparison with treatments they have already tried and failed is therefore futile.

However, to help put this remarkable result in perspective, in a cohort of patients with spinal stenosis, satisfaction scores of 50–70% after surgical fusion are considered successful.1

The proportion of patients reporting the highest level of satisfaction (“very satisfied”) with their treatment dropped (73–60%) from 90 days to one year. Do you know why this is the case? Do you suspect it will drop further or stabilise moving forward?

This fluctuation represents only a small proportion of patients. Several studies have shown that as patients over time get used to their improved state of being, their perception of inconveniences recalibrates as well.

It is important to note, however, that in this study the overall satisfaction remained stable at 81% as did the 81% of patients who reported a clinically important improvement in one or more of the key outcome measures. Based on my personal experience with those patients coming up to two years, I am not at all concerned with this. But, only the two-year results will confirm this for the entire study population.

How was this study limited?

This study has a single-arm design and, therefore, the outcomes have been compared to baseline rather than a control group. However, the fact that the improvements in outcome measures are sustained beyond the one year follow-up is a very positive sign. Long-term data collection is ongoing and will continue to be reported. In the meantime, we are well on track with the enrolment of the ReActiv8-B trial which is a randomised, sham-controlled and blinded study which will provide Level-1 evidence.

When do you expect the results of the ReActiv8-B trial to be available, and what are your hopes for the data?

We are very encouraged by the rapid enrolment of the ReActiv8-B trial both based on our own experience and also from what we see going on in the other international study sites. The company has indicated that results could be available in 2018.

The hopes are that, depending on the data, we can expand our spinal treatment portfolio with a new successful minimally invasive therapy.

Do you think that this technology has the potential to become a common treatment for low back pain?

In our group in Antwerp, Belgium, we have come to the realisation that there is a role to play for surgery, neuromodulation and restorative neurostimulation such as ReActiv8. In fact, our multidisciplinary spine unit is currently being reshaped around this philosophy.

References

  1. Försth P et al. New England Journal of Medicine 2016; 374(15); 1413–23