Actipatch for management of localised musculoskeletal pain

Transcription

1 Northern Treatment Advisory Group Actipatch for management of localised musculoskeletal pain Lead author: Daniel Hill Regional Drug & Therapeutics Centre (Newcastle) November

2 Summary Analgesics are only effective in a small proportion of patients with chronic pain. Nonpharmacological treatment may be effective in reducing long-term pain and disability in some people with chronic pain, and can be used to augment and complement analgesic use. ActiPatch is a wearable pulsed electromagnetic field device for the management of localised musculoskeletal pain. In a small RCT in patients with osteoarthritis of the knee (n=60), one month of treatment with the ActiPatch device was associated with a reduction in pain and WOMAC score compared with placebo. A registry study evaluated efficacy of the device in subjects with chronic musculoskeletal pain due to a variety of aetiologies. After using a trial device for seven days, 65% of subjects reported a benefit from the trial device, with an average pain reduction in these individuals of 57%. A three month follow-up survey showed sustained pain relief; decreased analgesic use and improved QoL. In a second registry study in subjects with chronic back pain, 52% of subjects reported a benefit from the trial device, with a mean pain reduction of 66%. Over the same period, 36% of subjects had a decrease in their medication use, and 14% stopped using pain medications. Due to the limitations of the registry design, the self-selected enrolment and self-reported nature of data collection, and the lack of a control group these findings should be interpreted with caution. No major adverse events associated with the ActiPatch device were reported during the placebo-controlled trial or in the two large registry studies. Minor issues concerning attachment of the device and a reaction to the adhesive medical tape were reported in some instances. In the chronic back pain registry study, increased pain was reported in 1.5% of individuals. Three versions of the ActiPatch device are available, with each product specifically tailored for the treatment of knee pain, back pain or muscle and joint pain. Each device has an on/off function and lasts for 720 hours. All three products can be purchased without prescription online and OTC at a retail cost of 20 to 25 per device. A refill device, supplied without any attachments is available for 20. The device was recently added to the NHS Drug Tariff at a cost of for each of the three products. A healthcare utilisation study assessed the impact of using ActiPatch as a chronic pain therapy on healthcare service use and direct costs to the NHS. This study has not been fully published, and therefore has not been subject to peer-review. Over a three-month assessment period, 61 subjects independently purchased 148 devices. Subjects reported a significant reduction in pain and an improvement in QoL which was associated with reduced utilisation of healthcare services as well as prescription analgesics. As a result, NHS costs were reduced by 8,664 over the three-month treatment period, which equated to 34,656 per year ( 568 per patient). The willingness of patients to purchase the device in the long-term has not been established. Given the data are limited to a small number of self-selected patients, and that the long-term efficacy of the device remains uncertain, consideration must therefore be given to whether the results can be suitably extrapolated to UK practice. The place in therapy remains unclear due to limited evidence base and uncertainty surrounding the clinical importance of unpublished trial findings. Northern Treatment Advisory Group, November

3 Introduction Chronic pain (also known as persistent pain or long-term pain) is a complex and debilitating condition, which has a substantial impact on the lives of those affected. In the absence of other criteria, chronic pain is usually defined as pain that has persisted for more than three months. Chronic pain can be associated with a number of different disease processes, previous trauma or injury. The prevalence of chronic pain is difficult to determine. In a recent systematic review, prevalence estimates ranged from 8.7% to 64.4%, with a pooled mean of 31%. 1 An earlier systematic review suggests that chronic pain in the UK affects between onethird and one-half of the population. 2 It has not been established what proportion of people with chronic pain have debilitating symptoms and seek support form healthcare services. Most patients with chronic pain first contact health services through primary care, and are subsequently managed in this setting, and even when patients are referred for specialist treatment, their ongoing care is likely to primarily remain with their GP. The management of chronic pain can present significant clinical challenges as there is considerable variation in patient responses to analgesia, both in terms of efficacy and side effects. 3 Although analgesics can be used effectively to relieve pain, this is only achieved in a small proportion of patients, and therefore prescribers must expect analgesics to fail for the majority of patients. 4,5 It is unusual for any analgesic, even strong opioids, to completely eliminate pain, so treatment should focus on reducing an individual's pain with a view to improving their overall quality of life (QoL). Non-pharmacological treatment may be effective in reducing long-term pain and disability in some people with chronic pain, and can also be used to augment and complement analgesic use as part of a multimodal therapy. 5,6 Nonpharmacological interventions for chronic pain include physical and psychological therapies and electrotherapies such as transcutaneous electrical nerve stimulation (TENS), and percutaneous electrical nerve simulation (PENS). ActiPatch (BioElectronics Corporation, USA) is a wearable pulsed shortwave therapy (PSWT) device for the management of localised musculoskeletal pain. 7 The CE marked class IIa device consists of a small module that houses the electronics and battery, connected to a wire loop antenna which is placed directly over the source of pain. The antenna is circular, soft and flexible and can be shaped to fit the area being treated as required. The device which weighs eight grams is held in place with wraps, adhesives, bandages or clothing, and can be used for up to 24 hours per day. The PSWT device delivers low energy electromagnetic pulses 1,000 times a second, but unlike a transcutaneous electrical nerve stimulation (TENS) machine; there is no sensation when using the device. In the UK, the ActiPatch device has been sold over-the-counter (OTC) for a number of years, and was added to the NHS Drug Tariff in May NICE guidance The National Institute for Health and Care Excellence (NICE) guidelines on chronic pain: assessment and management are currently in development, with an expected publication date of January This guideline will cover adults and young people (16 years and over) with chronic pain. One part of the guideline will cover specific pharmacological and nonpharmacological interventions for chronic primary pain conditions for which there is no existing NICE guidance. It is not yet known whether this guidance will include specific Northern Treatment Advisory Group, November

4 reference to the ActiPatch device. 8 However the manufactures are submitting an application for ActiPatch to be included in this NICE guidance. There is no interventional procedures guidance by NICE specifically for the ActiPatch device. The NICE guidelines on low back pain and sciatica in over 16s (2016) states that patients should not be offered the use of electrotherapies including TENS and PENS for managing low back pain with or without sciatica. 9 The NICE guidelines on osteoarthritis recommend that healthcare professionals should consider the use of TENS as an adjunct to core treatments for pain relief. 10 Clinical evidence Osteoarthritis of the knee The efficacy of ActiPatch in the management of pain in patients with primary osteoarthritis (OA) of the knee was evaluated in a randomised, double-blind placebo-controlled trial. 11 Subjects aged >40 years were included if they had radiographic evidence of knee OA and persistent pain higher than 40 mm on the visual analogue scale (, mm range) for global pain despite receiving the maximal tolerated doses of conventional medical therapy, including paracetamol and/or an NSAID. Exclusion criteria included secondary causes of OA, infection, secondary fibromyalgia, systemic arthritis, diabetes, patients receiving anticoagulant therapy, or previous intra-articular steroid injections. Sixty-six subjects were randomly allocated a wearable PSWT device (ActiPatch) or a placebo device with no electromagnetic properties. Subjects were trained in the use of the device, which was used consecutively with the antenna placed over the knee for a minimum of 12 hours daily treatment for one month. The device was kept in place with a wrap and switched off when not in use. Subjects continued to take prescribed NSAIDs/analgesics as needed. The primary outcome measure was the reduction in pain intensity, assessed through (Visual analogue scale) and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores. Secondary outcomes included QoL measured through the SF-36 questionnaire, pressure pain threshold (PPT), and changes in intake of NSAIDs/analgesics. A total of sixty subjects completed the study, as three subjects in each group were lost to follow-up. The baseline demographics and clinical characteristics of the two groups were comparable, and during the study, the rates of compliance with the device were similar. After one month of treatment, there was a significant reduction in pain scores for subjects using the PSWT device compared to those who received the placebo device (25.5% vs. 3.6%; standardised effect size (95% CI to -0.19). Likewise, PSWT treatment was associated with a significant reduction in WOMAC pain scores compared with placebo (23.4% vs. 2.3%; effect size (95% CI to -0.09). Pain tolerance and physical health scores also improved in PSWT-treated patients compared to placebo, but there was no significant difference in mental health scores. In the PSWT group, 26% of subjects stopped previously prescribed NSAID/analgesics, whereas in the placebo group 3% stopped, and 10% started new therapy. General chronic pain A registry study evaluated the efficacy of ActiPatch in a broader population of subjects with chronic musculoskeletal pain in different locations due to a variety of aetiologies. 12 A registry Northern Treatment Advisory Group, November

5 of 44,000 subjects from the UK or Ireland who submitted a request via the ActiPatch website to try a trial device was established between July 2014 and April All subjects paid a small fee for the device which was shipped to their home. The trial device, once activated had a seven-day power supply and is recommended to be used continuously for the seven days. Three-to-four weeks after receiving the trial device subjects were ed a webbased assessment form, with a second reminder six days later. Details of design and content of the assessment form were not reported. The trial device was considered effective or of benefit when there was a reported minimum two-point reduction in the pain scores (0-10 scale). A total of 5,002 responses were received, equating to a response rate of approximately 11%. All responses were included in the analysis, with the exception of 250 responses that included comments that stated the trial device had not been received or used. The majority of responders were over the age of 35, and 74% were female. The most frequently reported causes of pain were OA (31%), rheumatoid arthritis (15%), fibromyalgia (15%), and sports injury (8%). In a number of cases multiple causes of pain were reported, with an overall average of 1.1 per subject. Multiple concurrent locations of pain were reported with an average of 1.7 per subject. The most frequently reported locations of pain were back (58%), knee (34%), and shoulder (26%), which corresponded overall with the most frequent areas of use at 44%, 21% and 14%, respectively. Baseline pain scores for all responders was an average of 8.02, despite the use on average of 1.97 pain treatments per subject. The most frequently used treatments were analgesic tablets (84%), topicals (32%), heat wrap (27%), TENS (20%), and physical therapy (19%). Overall, NSAIDs (48%) and paracetamol (43%) were the most frequently used medications. Using the two-point reduction criteria for determining effectiveness, 65% of all subjects reported a benefit from the trial device, with an average pain reduction in these individuals of 57%. In those subjects experiencing persistent pain for greater than six months (4,308 responses) the percentage reporting benefit was fairly consistent across all major areas of the body and all causes of pain (table 1). The percentage of subjects reporting that the trial device was beneficial was largely matched by those indicating an intention to purchase (49%) or maybe purchase (22%) the retail device. A three month follow-up survey was sent to those subjects who had previously reported an intention to purchase or maybe purchase the retail device. 12 From a total of 658 responses, the indicated purchase rate was 80%, with around half of those not purchasing the device indicated that the reason was financial limitations. Long-term pain control was established with 93% of responders reporting sustained pain relief. Pain levels at the three month time point were on average 3.99 points or 51% lower than the reported baseline. A moderate to great improvement in QoL was reported by 84% of subjects, and medication use was reduced on average by 50%. Northern Treatment Advisory Group, November

6 Table 1. Pain reduction and effectiveness in relation to location of use and by cause of pain in those reporting chronic pain >6 months. Effectiveness and pain reduction in relation to location of use Location Response number Benefit (%) Baseline Trial device difference Pain reduction (%) Back 2, ± ± Knee ± ± Neck ± ± Shoulder ± ± Hip ± ± Other ± ± Effectiveness and pain reduction by cause of pain Aetiology Chronic back pain Response number Benefit (%) Baseline Trial device difference Rheumatoid arthritis ± ± Osteoarthritis 1, ± ± Fibromyalgia ± ± Sports injury ± ± Postsurgery pain ± ± Tendonitis ± ± Neuropathic ± ± Other 1, ± ± Pain reduction (%) A second registry study evaluated the efficacy of ActiPatch in subjects with chronic back pain (CBP). 13 A registry of 31,125 subjects from the UK or Ireland who submitted a request via the ActiPatch website to try a trial device was established between January and May After receiving the trial device subjects were ed an assessment form, with a second reminder four days later. The assessment was designed to collect data on age, gender, pain level, duration of pain, location and cause of pain. In addition, the study collected data on a wider analgesic profile including adverse effects and their impact on QoL, and any change in medication use after using the device. The trial device was considered effective if the pain score was reduced by at least 40%. A total of 3,735 individuals completed the assessment, equating to an overall response rate of approximately 12%. Of this group, 1,394 subjects indicated that they used the device for CBP. The majority of responders were female (75%), over the age of 35 and experiencing long-standing pain of two or more years with a median of 6.1 years. The most frequently reported causes of pain were disc issues (18.0%), OA (13.7%), sciatica and fibromyalgia (both 11.8%). In a number of cases multiple causes of pain were reported, with an overall average of 1.57 per subject, and some of these were therefore not related to CBP. The mean baseline pain reported by the CBP subjects before using the trial device was 8.04 ± The most commonly used analgesics were NSAIDs (46%), paracetamol (52%), weak opioids (30%) and amitriptyline (29%), with subjects using on average 2.5 different pain medications. Many responders indicated that they were also using other treatment modalities such as TENS, heat wraps and physical therapy. Overall, 39.3% of subjects reported good or Northern Treatment Advisory Group, November

7 adequate pain relief from pain medications. Of the 996 responders asked about the possible adverse effects associated with their pain medication, 66.1% reported experiencing adverse events, with a mean negative impact on their QoL of 5.7 on a 0-10 scale. After using the trial device for seven days, the mean pain score was 4.83 ± 2.66, or a difference of 39.9% (3.21 points) compared to baseline (p<0.001). Using the 40% minimum reduction criteria for determining effectiveness, 52% of CBP subjects reported a benefit from the trial device, with a mean pain decrease of 5.40 points, or 66% reduction in pain. In the prior registry study of general chronic pain sufferers, a two-point reduction on the mean pain score was set as the threshold for effective pain relief. Using this 2-point reduction for the current study, 66% of the CBP subjects meet these criteria and average a 58% reduction in pain. Intent to continue the use of the device was closely associated with the degree of reduction, with only 31.2% of subjects indicating that they would probably- or definitely not continue the therapy. Over the seven day trial period, 36% of CBP subjects reported a distinct decrease in their medication use, and 14% were able to stop using pain medications. Limitations of the evidence There is only one small placebo controlled trial (n=60) evaluating the ActiPatch for use in OA of the knee. Patients were only followed up for one month; this is not a sufficient period of time to evaluate the efficacy of the device for a chronic condition. Furthermore the study is only in comparison to placebo and patients continued to take analgesic medications. However there was no consistency in the other analgesia that was taken. 11 The other trials are registry studies that do not have a control group, are self-selected and self-reported studies. 12,13 Patients who did not respond to the ActiPatch and stopped using it may have been less likely to complete the survey than a patient who did benefit from it. The registry studies did not assess the long term efficacy of the devices despite their use for chronic pain. The length of time the patients used the devices per day was not controlled as in the placebo controlled trial. Patients continued to take analgesia medications throughout the studies. However the dose and frequency was not stated therefore it is unknown if these doses were therapeutic. In addition there was no placebo used in the studies. A comparison was taken between periods with or without the patch. Therefore any benefit from the patch may have been due to a placebo effect that may have been negated if the studies had a longer follow up period. None of the studies had a direct comparison to an equivalent non-pharmacological device such as TENS or PENS devices. Patients were able to use these devices in the registry studies alongside ActiPatch but with no consistency. Therefore the findings of these studies should be interpreted with caution. The place in therapy remains unclear due to limited evidence base and uncertainty surrounding the clinical importance of registry studies and unpublished trial findings. Northern Treatment Advisory Group, November

8 Safety No adverse events associated with the PSWT device were reported during the placebocontrolled trial in patients with primary OA of the knee. 11 In the chronic musculoskeletal pain registry study, no major adverse events associated with the PSWT device were reported. 12 Minor issues concerning attachment of the device and a reaction to the adhesive medical tape were reported in 0.4% of the responses. In the chronic back pain registry study, no significant adverse events associated with the PSWT device were reported. 13 Increased pain was reported in 1.5% of individuals and an adverse reaction to the medical adhesive tape was reported in less than 1% of individuals. Cost analysis The ActiPatch device was added to the NHS Drug Tariff in May 2018 (Part IXA-Appliances) at a cost of each for the knee pain, back pain, or muscle and joint pain products. Prescriptions in primary care will be subject to a single activity fee of 1.29 per prescription, whilst those made in secondary care may be subject to VAT. If worn continuously one device will last for one month. The prices below (Table 2) take into consideration how long the device is worn for. All three ActiPatch products can also be purchased without prescription online and OTC at some local pharmacies at a retail cost of between 20 and 25 per device (720 hours of therapy). A refill device, supplied without any attachments is available for 20. Table 2. ActiPatch device cost per patient. One month (24 hours/day) One month (8 hours/day) Twelve months (24 hours/day) Twelve months (8 hours/day) Primary Care Secondary Care (Inc. VAT) OTC / Online An ActiPatch trial device can be purchased directly from the manufacturer at a cost of 4.95 inclusive of postage. The trial device, once activated has a seven day power supply and cannot be turned off. Only two trials are permitted per household and only one trial permitted per user. In the UK, chronic pain is estimated to affect between one-third and one-half of the population. 2 It has not been established what proportion of people with chronic pain seek support from healthcare services. The treatment of chronic pain is costly to the NHS. In 2016, 537 million was spent on prescribing analgesics, with at least an additional 50% cost incurred from the prescription of other drug classes such as antidepressants and antiepileptic drugs. 8 Additional healthcare costs include visits to primary care, referrals to secondary care, and the costs of investigations and interventions, including surgery. According to the Royal College of General Practitioners (RCGP), people with chronic pain consult their GP around five times more frequently than those without, and chronic pain is a presenting condition in around 22% of consultations. 14 Northern Treatment Advisory Group, November

9 Healthcare utilisation study A healthcare utilisation study assessed the impact of using ActiPatch as a chronic pain therapy on healthcare service use and direct costs to the NHS. This study has not been fully published, but a document presenting the results of the study is freely accessible on the manufacturer s website. 15 The study included 61 adults with severe chronic pain, defined as pain score of at least six out of a maximum possible ten for at least three consecutive months. Data on pain scores, QoL and utilization of healthcare services were measured for each subject during two time periods, each lasting three-months; the first period served as a baseline measure (control), while the second period served as an intervention measure in which ActiPatch was incorporated as a chronic pain therapy. Utilisation of healthcare services was documented using the number of visits to GPs, Pain Specialists and/or other healthcare professionals involved in chronic pain management such as physical therapists. Additionally, the amount of time each subject spent with their GP discussing their pain, and the use of prescription analgesics was also documented. The reference cost of NHS services was calculated from published data, and the cost of analgesics from the NHS formulary. The majority of subjects were female (82%), over the age of 35, with a mean pain duration of 8.9 years. The most frequently reported cause of pain was OA (36%), with a number of subjects reporting multiple causes. The device was predominantly used for treatment of back (45%) and knee pain (45%). The mean baseline pain reported by subjects before using the trial device was 7.93 ± 1.4, which is consistent with aforementioned registry studies. After using the device for three months, the mean pain score was 5.07 ± 2.5, or a difference of 36.6% (2.86 points) compared to baseline (p<0.001). Subjects also reported a statistically significant improvement in QoL as measured by Oswestry Disability Index (p<0.001). Over the three-month baseline period (B-3M), 43 subjects regularly visited their GP which amounted to a total of 135 appointments. During the three-month ActiPatch assessment period (A-3M), 28 subjects had an appointment with their GP, resulting in a total of 58 appointments, which represents a 57% decrease. Of the 43 subjects who visited their GP, both total time (61%) and average time (40%) spent talking about pain were reduced in the A-3M period. During the B-3M period, there were 18 appointments with a pain specialist compared to seven appointments during the A-3M period. The total number of appointments with a physical therapist during the B-3M period was 92 which decreased to 39 during the A- 3M period. At B-3M, 41 subjects were on prescribed analgesic medications compared to 32 in the A-3M period. Subjects were using on average of 1.3 different pain medications at B-3M which was reduced to 0.9 per subject at A-3M. Subjects also reported a distinct reduction in their prescription medication use with an average reported reduction of 38%. The 61 subjects enrolled in this study independently purchased 148 devices over the three-month period, at a retail cost of between 20 and 25 per device. The overall cost to the NHS for healthcare services provided to each subject was calculated by multiplying the number of appointments with the costs for each service (table 3). During the A-3M period, utilisation of healthcare services by the subjects was markedly lower than during the B-3M period, which corresponds to a reduction in NHS costs of 7,540. Over the same period, total analgesic prescription costs were reduced by 1,124. This equates to an overall reduction in Northern Treatment Advisory Group, November

10 NHS healthcare costs of 8,664 during the three-month period, or 34,656 per year ( 568 per patient). If the cost of the ActiPatch devices used in this study was borne by the NHS this would amount to 2,065 (148 x 13.95) over the three-month period. If subjects continued to use the device at the same rate, the projected one-year NHS treatment cost for all 61 subjects would be 8,664. After accounting for the cost of the device the overall reduction in NHS healthcare costs would be 6,599 during the three-month period, or 26,396 per year ( 432 per patient). Table 3. Total NHS healthcare cost comparison between the baseline and ActiPatch threemonth assessment periods in 61 patients - (Self-funded vs. NHS funded). Service/ Resource Use B-3M Cost ( ) Reference cost of appointment: GP 45, Pain Specialist 125, and Physical Therapy 45. *Inclusive of total device cost to NHS for one year of 8,258 A-3M Cost ( ) Cost Difference ( ) GP 6,075 2,610-3,465 Pain Specialist 2, ,375 Physical Therapy 4,140 1,440-2,700 Analgesics 3,189 2,065-1,124 Self-funded device TOTAL (3 month) 15,654 6,990-8,664 TOTAL (1 year) 62,616 27,960-34,656 NHS-funded device Actipatch Device 0 2, ,065 TOTAL (3 month) 15,654 9,055-6,599 TOTAL (1 year) 62,616 36,220-26,396* Points to consider The overall clinical benefit of ActiPatch is difficult to estimate based on the available evidence. There is only one RCT (n=60) that supports the use of ActiPatch. However there are a number of limitations to this study, including the study size and the length of the study. There are no RCTs comparing the efficacy of ActiPatch in comparison to other non-pharmacological interventions for chronic pain. The results from the registry studies and healthcare utilisation studies should be interpreted with caution due to the nature of the study designs. The long term safety and efficacy of the ActiPatch is unknown. NICE will published guidelines regarding non-pharmacological interventions in chronic pain conditions in It is not yet known if the ActiPatch will be included in this guidance. Patients are able to buy the ActiPatch themselves online or via some pharmacies for a cost of between The cost of the ActiPatch in the drug tariff is Northern Treatment Advisory Group, November

11 Author s declaration. The lead author has no relevant interests to declare. References 1. Steingrimsdottir OA et al. Defining chronic pain in epidemiological studies: a systematic review and meta-analysis. Pain 2017;158: Fayaz A et al. Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies. BMJ Open 2016;6:e Scottish Intercollegiate Guidelines Network SIGN 136 Management of Chronic Pain. december National Institute for Health and Care Excellence. Key therapeutic topic: Medicines optimisation in long-term pain (KTT21). Last updated February British Medical Association. Chronic pain: supporting safer prescribing of analgesics. March Chang KL et al. Chronic pain management: nonpharmacological therapies for chronic pain. FP Essent 2015;432: BioElectronics Corporation. ActiPatch. Accessed 11/06/ National Institute for Health and Care Excellence. Guideline scope. Chronic pain: assessment and management. Accessed 15/06/ National Institute for Health and Care Excellence. Guideline [NG59] - Low back pain and sciatica in over 16s: assessment and management. November National Institute for Health and Care Excellence. Guideline [CG177] - Osteoarthritis: care and management. February Bagnato GL et al. Pulsed electromagnetic fields in knee osteoarthritis: a double blind, placebocontrolled, randomized clinical trial. Rheumatology (Oxford) 2016;55: Rawe IM et al. A UK registry study of the effectiveness of a new over-the-counter chronic pain therapy. Pain Manag 2015;5: Staelin R et al. An over-the-counter central sensitization therapy: a chronic back pain registry study of pain relief, medication use and their adverse effects. Pain Manag 2017;7: Royal College of General Practitioners. Chronic Pain. Accessed 18/06/ BioElectronics Corporation. ActiPatch. Healthcare Utilization Study Northern Treatment Advisory Group, November