8. What is in the FLEXISEQ® products?
All products contain tiny lipid spheres (Sequessome™ vesicles) in a watery gel. These spheres can pass through the skin into the joint below.
FLEXISEQ® (OA) and FLEXISEQ® Active composition: Aqua, Phosphatidylcholine, Alcohol, Glycerin, Carbomer, Polysorbate 80, Disodium Phosphate, Sodium Hydroxide, Benzyl Alcohol, Methylparaben, Ethylparaben, Linalool, Disodium EDTA, Sodium Phosphate, Sodium Metabisulphite, BHT
9. How well do the FLEXISEQ® products work?
There have been 5 clinical studies evaluating the safety and efficacy of FLEXISEQ® across a range of doses representative of the three products, and these consistently demonstrated reductions in pain of around 50% and improvements in physical function of around 40%i, ii, iii
One of the key studies in this extensive clinical programme also demonstrated that FLEXISEQ® is as effective at alleviating joint pain as a leading oral prescription drug which, unlike FLEXISEQ®, but in common with other treatments in this same class of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), has well recognised systemic side effects (problems resulting from the drug being spread throughout the body). In this comparison study, patients treated with FLEXISEQ® reported a reduction in joint pain and stiffness that was equivalent to that reported by the patients taking oral celecoxib.ii
These same studies have also demonstrated the safety of FLEXISEQ® products: the most commonly reported side effects were mild/moderate skin irritations. In addition, there have now been over 50 million applications of the product and, unlike other oral and topical treatments, there have been no reported incidences of systemic side effects (such as heart attacks, strokes and gastro-intestinal problems linked to NSAIDs) related to the use of FLEXISEQ. This lack of systemic exposure also makes these products safe to use alongside any other therapy.
As with all treatments, if you have any concerns, please consult a doctor or pharmacist.
12. How should I apply the gel?
FLEXISEQ® products should be applied twice daily to the affected joint, usually in the morning and the evening. Use enough gel to evenly cover the soft tissue around the joint.
For the knee: a twice daily dose of 2.2 g corresponding to approximately 7 cm line of gel as squeezed from the tube is recommended. The gel should not be applied to the patella (knee cap) and should include the area at the back of the knee. FLEXISEQ® must be allowed to dry before covering; drying should take no longer than 10 minutes if the product is applied to clean, dry skin. If drying takes longer than this, ensure that the skin is dry (for example if applying after a bath or shower) and try using a little less gel. If the drying time is considerably less than 10 minutes then a little more gel should be used next time. Please wash your hands after applying the gel.
For the hip: Locate the edge of your pelvis (or hipbone) at your side and apply the gel approximately two inches below where you can no longer feel bone but soft tissue. Do not spread towards the buttocks but instead towards your centre line. It is difficult to give precise dosing amounts for the hip as the size of this joint can vary widely from patient to patient. If you consider yourself to be of average weight, use approximately 3 g (approximately 10 cm line of gel as squeezed from the tube) to cover an area of approximately the size of your hand. If you believe you are above average size, you may need to apply a little more. You will know if you have applied the correct amount as it should take around 10 minutes to dry. For the first few applications the amount applied may need to be increased or decreased to achieve a 10 minute drying time. In order to achieve optimum effect, FLEXISEQ® gel should be applied twice daily to the whole affected joint, not rubbed in but left to dry. The joint should not be covered until the gel has completely dried. Please wash your hands after applying the gel.
For the hand: It is difficult to give precise dosing amounts for the hand as the actual joints affected vary from patient to patient. As a guide, approximately 1 g (3 cm line of gel as squeezed from the tube) would be adequate to treat the knuckles across one hand. You should apply the gel to the entire affected area and you will know if you have applied the correct amount as it should take around 10 minutes to dry (although may remain tacky after this time). For the first few applications the amount applied may need to be increased or decreased to achieve a 10 minute drying time. In order to achieve optimum effect, FLEXISEQ® gel should be applied twice daily to the skin around the joint, not rubbed in but left to dry. The joint should not be covered until the gel has completely dried. Please avoid washing the affected hand for 30 minutes after application.
For the shoulder: It is difficult to give precise dosing amounts for the shoulder as the size of this joint and location of the pain varies from patient to patient. If you consider yourself to be of average weight, use approximately 2.2 g corresponding to approximately 7 cm line of gel as squeezed from the tube to cover the area corresponding to the location of your pain. If you believe you are above average size, you may need to apply a little more. You will know if you have applied the correct amount as it should take around 10 minutes to dry (although may remain tacky after this time). For the first few applications the amount applied may need to be increased or decreased to achieve a 10 minute drying time. In order to achieve optimum effect, FLEXISEQ® gel should be applied twice daily to the whole affected joint, not rubbed in but left to dry. The joint should not be covered until the gel has completely dried. Please wash your hands after applying the gel.
16. What are the differences between FLEXISEQ® and other pain treatments?
Unlike most pain treatments, FLEXISEQ® treatments are drug-free and therefore have an excellent safety profile. They can be used in patients with other conditions and who take medication. FLEXISEQ® has been shown to be as effective at alleviating joint pain as the oral prescription drug, celecoxib (an oral NSAID).ii
FLEXISEQ® has a physical mode of action, while NSAIDs have a pharmacological effect and alter physiological pathways in the body. NSAID use is often associated with gastrointestinal (GI) side effects such as ulcers,iv, v and cardiovascular effects such as increased risk of a heart attack and these side effects can be very serious.vi, vii In contrast, the side effects most commonly reported for FLEXISEQ® are mild or moderate skin irritations i, ii, iii that are temporary and usually resolve over time without stopping treatment.
There is increasing awareness that oral NSAIDs are not suitable for patients with certain other conditions (such as heart disease, asthma and stomach ulcers), or those who are on specific medications or are elderly. These patients will therefore benefit from the availability of this drug free, effective topical treatment, FLEXISEQ®, which is not an NSAID. Patients already taking NSAIDs may also use FLEXISEQ® in combination if additional pain relief is required, whereas topical NSAIDs cannot be used alongside oral NSAIDs at the same time. More details about the concerns with NSAIDs can be found at the National Institute for Health and Care at http://cks.nice.org.uk/nsaids-prescribing-issues.
18. How does FLEXISEQ® work?
FLEXISEQ® treatments are drug-free and relieve the pain and stiffness associated with osteoarthritis. FLEXISEQ® exerts its pain-relieving effect via lubrication of the joint which is a physical mode of action. It has no pharmacological, metabolic or immunological activity. FLEXISEQ® is a gel containing Sequessome™ vesicles, which are tiny lipid spheres. As the gel dries on the skin, these spheres change their shape and pass through the skin, then into the joint where they lubricate the surface of the cartilage to provide relief from pain and stiffness. They are compressible and deformable, yet stable.
Patients with joint disorders such as OA have been found to have reduced levels of lubricants in their synovial fluidviii and this is one of the factors contributing to the pain and loss of joint function in patients with OA.ix There is also strong evidence in published literature that liposome vesicles can act as a bio-lubricant in the knee joint, and hence can reduce pain and improve mobility.ix
Research has shown that following topical application of FLEXISEQ®, the Sequessome™ vesicles pass through the skin and penetrate the synovial fluid within the joint where they collect on cartilage surfaces.x The physical properties of the Sequessome™ vesicles make them particularly efficient at lubricating.
i Kneer W, Seidel EJ, Mazgareanu S, Rother M. J Pain Res 2013;6:743-753
ii Conaghan P, Dickson J, Bolten W, Cevc G, Rother M. Rheumatology 2013 Jul; 52(7):1303-12
iii Rother M, Conaghan PG. J Rheumatology 2013 2013;40:1742-48
iv NICE, 2008. Available at: www.nice.org.uk/CG059 (accessed 27 February 2012).
v McKenzie S, Torkington A. Aust Fam Physician 2010;39(9):622–625.
vi Coxib and Traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;pii: Q5 S0140-6736(13)60900-9
vii Fosbøl EL, Gislason GH, Jacobsen S, et al. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study. Clin Pharmacol Ther 2009;85:190-7
viii Hills BA, Monds MK. Br J Rheumatol 1998;37:143–147.
ix Vecchio P, Thomas R, Hills BA. Surfactant treatment for osteoarthritis. Rheumatology 1999;38:1020−1021
x Yurdakul S, Baverstock N, Mills J. Localisation of fluorescently labelled drug-free phospholipid vesicles to the cartilage surface of rat synovial joints. ICOOMD, London 2015
xi Clinical study report (sponsor code CL-033-III-05). IDEA AG, Frankfurter Ring 197a, 80807 Munich, Germany. 15 December 2008
xii Rother M, Yeoman G, Ekman E. Annual EULAR Congress 2012b Abstract no. EULAR12-3375
xiii National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 2010. Osteoarthritis. Available at: www.niams.nih.gov/health_info/osteoarthritis/ (accessed 27 February 2012).
xiv Kneer W, et al. Curr Drug Saf 2009;4:5–10.