71 - Real-World Outcomes from High-Dose Transcutaneous Electrical Nerve Stimulation in Individuals With Chronic Knee Pain

NeuroMetrix, Inc., Woburn, MA, USA

Purpose
About one-quarter of adults suffer from frequent knee pain, which limits function, decreases mobility and impacts quality of life. Osteoarthritis, affecting 30 million adults in the U.S., is the most common cause. Patients with chronic knee pain may be managed with opioids and non-steroidal anti-inflammatory drugs. However, these medications are not uniformly effective, have side effects and, in the case of opioids, may cause addition. Total knee arthroplasty (TKA) is a surgical option for some patients, however it has a long recovery time, is a costly procedure and may require prolonged post-operative pain management. For these reasons, there is a need for non-pharmacological analgesic options for chronic knee pain.
Transcutaneous electrical nerve stimulation (TENS) is a non-invasive treatment for chronic pain. Conventional TENS is delivered through surface electrodes, placed near the site of pain, to generate a strong paresthesia. The resulting stimulation of large diameter, deep tissue afferents produces transient analgesia. A possible mechanism of action is a reduction in central excitability and enhanced descending pain inhibition. TENS has been prescribed for chronic knee pain for several decades. However, recent meta-analyses on its clinical benefits are inconclusive. A likely contributor to the variability in study results is under dosing. TENS devices are generally designed for stimulation anywhere on the body through wired electrodes. This methodology can be cumbersome and complicate use during daily activities and sleep. In most studies, TENS use has been limited to 30-60 minutes per day, several times a week. Furthermore, objective compliance monitoring has rarely been utilized which creates further uncertainty on study fidelity. Recently, wearable TENS devices have been developed for extended use that do not interfere with daytime activity and sleep. These devices provide high-dose TENS, which may be defined as regular (i.e., at least 3-4 days week) stimulation for several hours. The purpose of the present study was to assess outcomes following up to 10-weeks of high-dose TENS use in individuals with chronic knee pain.
Methods
This retrospective, real-world study evaluated users of a wearable TENS device (Quell^®, NeuroMetrix, Woburn, MA). The device is placed on the upper calf and provides semi-continuous nerve stimulation (60 minutes every other hour) at an intensity that is calibrated to a strong, nonpainful sensation. The device and a companion mobile app collect demographics, pain characteristics, pain measures and usage data provided by users who opt-in to research participation. The data is uploaded to a cloud database. Data analyses are performed on an anonymized version of the database.
Eligible users were those that provided demographic, clinical and pain data prior to initiating therapy. A subset meeting the following criteria were included: a) pain duration greater than 3 months, b) pain frequency at least several times a week, c) baseline pain intensity at least 4 on an 11-point numerical rating scale (NRS), d) self-reported knee pain and e) stimulation on at least half of the 70-days following the start of TENS.
The study evaluated two outcomes measures. Pain intensity was assessed on an 11-point NRS. Functional impairment was assessed with a subset of the BPI-SF pain interference domain. The sleep, general activity and mood items were averaged to form a composite functional impairment indicator between 0 and 10. The pain intensity and pain interference ratings were provided voluntarily at the user’s discretion and reflected overall pain rather than for a specific anatomical site. Both outcome measures were assessed at baseline and as close to 70-days following the start of TENS as available, using an intention-to-treat analysis. The baseline pain and functional impairment ratings occurred on the first day of device use or within the prior 6 days (latest one used). The follow-up rating was taken as that closest available to day 70. If there was no follow-up rating then the value was imputed using the baseline observation carried forward method. The changes in pain intensity and functional impairment were defined as the baseline subtracted from the follow-up. The mean group change was calculated across all participants and compared to the null hypothesis of no change using the one-sample t-test.
Results
A total of 1136 device users met the inclusion criteria. Study participants had a mean age of 58 (SD 13) years, 61.1% were female and the mean BMI was 31 (SD 8) kg/m2. Participants self-reported a mean of 5.7 (SD 2.6) pain sites and 4.4 (SD 2.5) painful health conditions. The most common self-reported conditions were arthritis (73%), prior leg injury (45%) and prior back injury (46%). Among those reporting arthritis, 62% specified osteoarthritis. Most participants (77%) reported chronic pain duration of at least 4 years. At baseline, the mean pain intensity was 6.8 (SD 1.6). Mean pain interference with sleep, activity and mood were 5.9 (SD 2.8), 7.3 (SD 2.1) and 6.5 (SD 2.5), respectively, which yielded a functional impairment score of 6.5 (SD 2.0). Pain sensitivity to weather was reported by 73% of participants.
Study participants used wearable TENS on 58 (SD 11) of the 70-day assessment period at an average of 7.0 (SD 2.6) hours per day. The average follow-up period was 50 (SD 29) days. A follow-up rating was imputed for 88 (8%) participants who only had a baseline rating. The follow-up pain rating was less than 30 days for 220 (19%) participants. The mean group change from baseline to follow-up was -1.0 (SD 2.3) for pain intensity and -1.4 (SD 2.5) for functional impairment, both p<0.001.
Conclusions
Consistent with earlier epidemiological studies of knee pain, the participants in this study were older adults, more likely to be female, tended to be overweight or obese, and had moderate to severe pain and substantial functional impairment. Knee pain was not an isolated symptom, as most participants reported additional pain in other body locations. The key study finding was that in an intention-to-treat population with chronic knee pain, high-dose TENS was associated with clinically meaningful group changes (i.e., 1-point or greater) in pain intensity and functional impairment.
Study strengths included the large, real-world sample which supports generalizability of the findings, the use of an intention-to-treat population to reduce bias from participants who stopped therapy early, and objective compliance monitoring to improve study fidelity. The study was limited by the lack of a control group against which to compare the change in pain measures. As a result, the relative contributions of specific effects from high-dose TENS and non-specific contributions from placebo and regression to the mean cannot be determined. Another limitation was that because the pain measures were not site-specific, the outcomes cannot necessarily be attributed to changes in knee pain.