Berlin 25.1013 "Get people moving – experience success". This slogan of the German Congress of Orthopaedics and Trauma Surgery also held true for the symposium organised by Pro Bono Bio, which reported on a new, innovative and award-winning therapy option for osteoarthritis patients. Studies were presented proving the efficacy of the topical gel for pain and joint stiffness associated with osteoarthritis as well as personal experiences of the presenters with FLEXISEQ™ based on patient cases. FLEXISEQ contains no pharmacologically active substances, but works through the use of Sequessome™ vesicles, tiny phospholipid droplets that penetrate the skin into the joint and lubricate the damaged cartilage. Worldwide marketing of the gel, developed and produced in Germany, is pending after initial successes in Europe and Asia, as company head John Mayo reported.
Alternative methods urgently needed for osteoarthritis treatment
Patients who suffer from osteoarthritis, a painful and chronic joint disease, have only limited treatment options. Apart from a change in lifestyle including weight reduction and controlled physical activity, the main treatment lies in the use of non-steroidal anti-inflammatory drugs (NSAIDs). These are, however, not effective for everyone, or, because of their possible contraindications, side effects or other restrictions, not generally suitable for administration. The Pharmaceuticals Commission of the Association of German Physicians recommends, in addition to paracetamol, topical non-steroidal anti-inflammatory drugs (NSAIDs) as the first choice in the treatment of osteoarthritis, where only daily doses of 3-4 g paracetamol are considered effective (Therapieempfehlung der Arzneimittelkomission der deutschen Ärzteschaft - Degenerative Gelenkerkrankungen – 3. Auflage 2008). The same is true for topical NSAIDs, only for a dose of 4 g diclofenac gel four times daily could a consistent effect be proven (Baraf et al 2011). Such an application, however, can already produce blood levels in the range of a low-dose therapy with oral NSAIDs (Kienzler et al. 2010; Hinz et al 2005).
The President of the Hessen Rheumatism League, Dr Wolfgang Bolten, knows first-hand the problems of patients with joint pain. "In the self-help groups, pain therapy in particular is discussed," he says. "Which anti-inflammatory drug works best? Which of them has the lowest rate of side effects? What other alternatives are available? One important topic in the discussion is the long-term safety of the analgesic medication they are using. Analgesics such as paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are the standard treatment. Reading the package leaflet or listening to patient experiences, however, gives an idea of the risk some patients are taking when they have to use these medications over long periods of time."
Substantial side effects with NSAIDs
"NSAIDs should be taken only in the lowest possible dose and for the shortest possible period," Dr Matthias Rother from Gräfelfing emphasised. "But the reality is very different!" Since NSAIDs are largely acquired and used without a prescription, patients with well-known risk factors like cardiovascular, gastrointestinal or nephrological diseases take these potentially dangerous drugs unmonitored, unfortunately frequently also in excessive doses. Only in July 2013 urgent safety information was issued based on corresponding study results regarding a new recommendation in dealing with diclofenac. Therefore, the drug is now contraindicated in patients with existing cardiac insufficiency, ischemic heart disease, peripheral arterial disease or cerebrovascular disease. Especially for elderly patients, who also suffer particularly frequently from osteoarthritis, several of these restrictions often apply. The fact that their complaints are not temporary but permanently present makes it more difficult. The effect of NSAIDs on the stomach is particularly dangerous. Thus the mortality rate for NSAID users who suffered gastrointestinal bleeding or perforation is 20.9 % (Straube et al. BMC Gastroenterol. 2009).
FLEXISEQ fills a therapeutic gap
A comprehensive clinical programme has proven the good efficacy of FLEXISEQ. In a key comparative study with celecoxib, pain relief was already achieved after two days, as co-researcher Dr Rother reported. The trial showed that in 1395 patients with gonarthrosis and moderate pain, the twice daily application of FLEXISEQ leads to reduced pain and stiffness and improved joint function, and just as effectively as the twice daily intake of 100 mg celecoxib, an NSAID frequently used for chronic pain (Conaghan et al 2013). The results of this study with celecoxib and placebo as comparison preparations are comparable to other studies, where FLEXISEQ showed consistent efficacy in alleviating pain and improving joint function in patients with arthritis of the knee joint (Stucki et al 2007; Rother & Conaghan 2013, Kneer et al 2013 in press).
Award-winning innovation: Sequessome Technology®
The novelty of FLEXISEQ comes from the Sequessome vesicles contained within, which are extremely deformable phospholipid spheres. Due to their high affinity to water, once the water from the gel evaporates, they penetrate into the intercellular spaces of the skin and through the underlying tissue layers. In this way they reach the synovial fluid and work there as a lubricant on the surface of the damaged cartilage structures, which have reduced natural lubrication in osteoarthritis patients. The pain is then alleviated and the joint function improved. This innovative approach of the Sequessome Technology, developed in Germany, was bestowed in January with the 2013 Innovation Award of the Federal Association of German Pharmacists (BVDA).
Conservative osteoarthritis therapy with innovative gel
FLEXISEQ expands the instrumentation for conservative therapy of osteoarthritis. Until now this has consisted of weight reduction and the removal of other risk factors, physical therapy and orthopaedics, but now with the help of FLEXISEQ even in difficult cases relief can still be achieved for the patient. Prof. Egbert Seidel of the Centre for Physical and Rehabilitative Medicine at the Sophien- und Hufeland-Klinik Weimar GmbH, said: "FLEXISEQ is used in our centre for multimodal pain therapy for multimorbid, chronic pain and osteoarthritis patients, for whom therapy with NSAIDs or opiates would only dramatically increase the risk of complications.
It works very well after four weeks; the pain is alleviated so that a moderate movement therapy can provide further improvement. After eight weeks the pain is halved on the 11-point VAS (0-10). Side effects could not be observed.
Apart from the pain reduction, every time a movement and function improvement are the goal, FLEXISEQ should be used. This also applies to patients who have only one risk factor with the intake of NSAIDs (anticoagulants, history of stomach ulcers, heart diseases, hypertension and many others). Thus FLEXISEQ broadens the spectrum of conservative therapies with few side effects in addition to medications and support devices for osteoarthritis patients."
German idea – international success
The idea for the innovative gel came from Germany. Today Pro Bono Bio, an international healthcare company, owns the rights to the Sequessome Technology. The gel, however, is manufactured in Germany. Mr Fasching of Aenova reported on the steep increase in demand for FLEXISEQ in every country where the gel is already available. In the near future, the market introduction of FLEXISEQ is planned for Malta, Great Britain, Sweden, South Africa, Turkey, Hong Kong, Singapore and Denmark. Martyn Smith of Pro Bono Bio, the manufacturer of FLEXISEQ, explained: "I'm delighted that FLEXISEQ is so successful. I am sure that it will have a crucial influence on patients' quality of life and will help them avoid the side effects caused by other therapies." In addition, Pro Bono Bio is working on several dermatological products based on Sequessome Technology.
Source: Satellite symposium held by Pro Bono Bio at the German Congress of Orthopaedics and Trauma Surgery in Berlin, 25.10.2013.