Advice
The technology
The technology
FLEXISEQ (often referred to as TDT 064 in the scientific literature) is an aqueous gel containing hydrophilic, nanoscale lipid vesicles with a phospholipid bilayer (Sequessome vesicles). The manufacturer claims that, because of their composition, Sequessome vesicles can pass through the skin to reach a joint. Sequessome vesicles are ultra-deformable, meaning that they are structurally robust and can stay intact while passing through the intercellular spaces of the skin (44 nm), despite their larger size (70 to 198 nm in diameter; Conaghan et al. 2014). The movement of these vesicles is said to be driven by the osmotic gradient between the surface of the skin and sub-dermal tissues (Cevc et al. 2003). FLEXISEQ is classed as a medical device because it has a physical mode of action and contains no active drug.
According to the manufacturer's instructions for use, FLEXISEQ should be applied twice daily, in the morning and the evening, to the soft tissues around the affected joint. Following application, it must be left to dry for at least 10 minutes before covering the area. As the gel dries, the water evaporates and this is reported to trigger the movement of the hydrophilic Sequessome vesicles through the skin, towards the aqueous environment of the synovial fluid within the joint.
The innovation
Although the analgesic mechanism of FLEXISEQ is unclear, the manufacturer claims that once localised in the joint, the Sequessome vesicles may act as a lubricant by coating the cartilage. Although a lubricant action would not be expected to provide an analgesic effect directly, the reduction in friction between cartilage surfaces may minimise further inflammation, and might reduce the release of fragments and debris from the damaged cartilage (Conaghan et al. 2014).
Current NHS pathway
Current treatments for osteoarthritis focus on managing symptoms such as pain because there is no medication that has been proven to prevent the disease or modify its course. According to the NICE guideline on osteoarthritis: care and management, healthcare professionals should take a holistic approach in assessing the impact of osteoarthritis on a person's function, quality of life, work, mood, relationships and leisure. Recommended core treatments for osteoarthritis are physical activity and exercise, weight loss (if the person is overweight or obese), and providing verbal and written information to increase the person's understanding of the condition. The use of locally applied heat or cold (thermotherapy) should be considered in addition to core treatments. Other options which can be considered include electrotherapy (transcutaneous electrical nerve stimulation [TENS]) for pain relief; advice on footwear for people with lower limb osteoarthritis; assessment for bracing, joint supports and insoles for people with instability; and use of assistive devices (for example walking sticks and tap turners).
Pharmacological management is also recommended in addition to core treatments to help manage pain. Paracetamol and/or topical non-steroidal anti-inflammatory drugs (NSAIDs) should be considered before oral NSAIDs, cyclo-oxygenase 2 (COX-2) inhibitors or opioids. Where paracetamol or topical NSAIDs do not provide enough pain relief, addition of oral analgesics (NSAIDs, COX-2 inhibitors and opioids) should be considered, taking into account individual patient risks (such as age) and potential benefits. Oral NSAIDs and COX-2 inhibitors should be used at the lowest effective dose for the shortest possible period of time.
The Medicines and Healthcare Regulatory Agency (MHRA) is currently reviewing non-prescription analgesics, after which time NICE will review the evidence on the pharmacological management of osteoarthritis.
Topical capsaicin cream can be considered in addition to core treatments for knee or hand osteoarthritis. For the relief of moderate to severe pain, intra-articular corticosteroid injections may be considered.
Referral for joint surgery is recommended for people if osteoarthritis has a substantial impact on quality of life and does not respond to non-surgical treatment.
Population, setting and intended user
Osteoarthritis is one of the most common chronic diseases in the UK, with 8.75 million people having sought treatment (Versus Arthritis). An estimated 4 million people in England have osteoarthritis of the knee and 2.5 million have osteoarthritis of the hip (Versus Arthritis).
FLEXISEQ is promoted for use by anyone with osteoarthritis and seems likely to be used in those for whom oral or topical NSAIDS are contraindicated, as an adjunct to other treatments for symptom management. FLEXISEQ is designed to be used in any setting, including at home by the patient and it should be applied according to the manufacturer's instructions for use.
FLEXISEQ is contraindicated for people with known sensitivity to any of its ingredients. It has not been tested on pregnant women in clinical trials, and therefore its use during pregnancy is not advised.
Costs
Device costs
The current retail list price for a 50 g tube of FLEXISEQ gel bought over the counter is £18.49 from UK high-street retailers (including VAT). Though not available on the NHS, the manufacturer is planning to apply for inclusion in the NHS Drug Tariff and states that an NHS prescription would cost £30.82 (excluding VAT) for a 125 g tube. The manufacturer claims that with the recommended application of twice a day, a 125 g tube will last for 28 days on average, but this will vary based on the number and size of joints being treated.
Costs of standard care
When FLEXISEQ is used as in addition to core treatments, it will add to immediate costs.
NICE's guideline on osteoarthritis: care and management groups standard care into 3 categories: core treatments (self-management, exercise and non-pharmacological treatments), pharmacological treatments and joint surgery. Adults with osteoarthritis are supported with non-surgical core treatments for at least 3 months before any referral for consideration of joint surgery (NICE's quality standard on osteoarthritis). In most cases the costs of self-management, exercise and weight loss programmes will be borne by individuals and not by the NHS and social care services. The unit costs of a 1 hour session of physiotherapy or occupational therapy are about £38 (PSSRU 2015). These unit costs cover a wide range of resources including labour time, facility overheads, facility capital and all clinical equipment. These unit costs are inclusive of mobility aids (shoe inserts, walking aids, bracing and tap turners) that physiotherapists and occupational therapists may supply. Thermotherapy can also be provided by these professionals (NHS website) and relevant costs are likely to be included in the clinical element. TENS can be recommended and the TENS machine and pads, which cost a total of around £35 (Lewis et al. 2015), can sometimes be loaned to patients (NHS website).
Pharmacological treatments can be considered as well as core treatments. Table 1 provides the costs of standard pack sizes and also the maximum monthly cost which assumes continual treatment for the month and was based on the maximum daily dose a patient should take. A GP appointment (unit cost for which is £45 (PSSRU 2015) will be required for prescription purposes with these treatments. In addition, the full cost of a corticosteroid injection will include the costed labour time of a hospital-based nurse or consultant. Assuming a 15 minute appointment these would add £10 or £34, respectively (PSSRU 2015).
Table 1: Pharmacological treatment unit costs
|
Pharmacological treatment |
Unit |
Pack cost |
Max monthly cost |
Source |
|
Oral analgesics (e.g. paracetamol) |
32 tablets (500 mg) |
£0.20 |
£1.40 |
BNF 2016 |
|
Topical NSAIDs (e.g. felbinac) |
100 g tube (30 mg per 1 g) |
£8.00 |
£56.00 |
BNF 2016 |
|
Topical capsaicin |
45g tube (250 mcg per 1 g) |
£17.70 |
£49.20 |
BNF 2016 |
|
Oral NSAIDs (e.g. dexibuprofen) |
60 tablets (400 mg) |
£10.00 |
£14.00 |
BNF 2016 |
|
Intra-articular injections (corticosteroid) |
1 100 mg vial of solution |
£0.90 |
N/A |
BNF 2016 |
A variety of surgical procedures can be used to treat severe osteoarthritis in different joints and unit costs will vary by procedure and joint. The most common cases are knee arthroplasty (knee replacement), hip arthroplasty (hip replacement) and resurfacing arthroplasty (NHS website). A UK evaluation comparing different knee prostheses stated the unit cost of the knee arthroplasty procedure (depending on brand and patient gender) ranged from £4,574 to £5,491 (Pennington et al. 2016). Another UK economic evaluation found the unit costs of hip arthroplasty and resurfacing hip arthroplasty were £6,091 and £6,275, respectively (Edlin et al. 2012).
Resource consequences
According to the manufacturer, FLEXISEQ has been available over the counter since 2013 and is not currently prescribable. FLEXISEQ is a topically applied gel and does not need special preparation, additional facilities or equipment. No other practical difficulties have been identified in using the technology.
No published evidence on the resource consequences of adopting FLEXISEQ in the relevant indication was identified in the systematic review of evidence. It is unclear if FLEXISEQ will be cost-effective for the NHS compared to standard care. In cases where FLEXISEQ is used as an add-on treatment, the immediate costs of treatment will increase. This may not be the case when it is used as a substitute for topical NSAIDs.