Specialist commentator comments

Advice

Five specialist commentators noted the limited evidence base for FLEXISEQ's physical and analgesic mechanism of action. One commentator questioned the plausibility of the migration of the Sequessome vesicles to the joint in significant amounts and for a sufficient amount of time to provide symptomatic relief. Another commentator suggested that the synovium and bone are more likely sources of pain in osteoarthritis than cartilage and questioned FLEXISEQ's analgesic mechanism of action. A third specialist commentator expressed concern that although FLEXISEQ is drug-free and may not have the risks associated with drug treatments, it could potentially accumulate in the joint. Another commentator highlighted the need for robust evidence of Sequessome vesicles localisation in the joint from in vivo models.

One specialist commentator felt that the clinical effectiveness of FLEXISEQ has not been demonstrated. The absence of an adequate placebo (an inactive topical gel) for FLEXISEQ was highlighted as a limitation by 3 commentators. One commentator said that without it, the clinical effectiveness of FLEXISEQ could be attributed to the placebo effect of rubbing a gel onto the knee, instead of the Sequessome vesicles reaching the joint. Another commentator noted that pooling the results from studies using different placebo treatments may introduce bias into the meta-analysis results.

Three specialist commentators recognised the importance of long-term studies for a chronic condition, such as osteoarthritis. Two commentators considered that studies with short-term follow-up are of value because many people experience osteoarthritis through flares (as opposed to constant symptoms) which they tend to treat at home for short-term periods, with the occasional use of topical gels or creams.

With regard to the FLEXISEQ indication, one specialist commentator clarified that patients unable to tolerate oral non-steroidal anti-inflammatory drugs (NSAIDs) can often tolerate topical NSAID therapy. Two commentators suggested that FLEXISEQ will most probably be used in combination with oral NSAIDs and other add-on therapies, with one of them noting that its additional benefit may be negligible. One commentator questioned the rationale behind the manufacturer's claim that although FLEXISEQ can be used by anyone with osteoarthritis, it would be most useful for people in whom NSAIDs are contraindicated, who have limited treatment options. The same commentator stated that in these people, the number of affected joints will be a deciding factor on potential benefit.

One specialist commentator noted that, in practice, paracetamol is currently considered as a less efficient NSAID and is not recommended as a first line therapy. Patients prefer to use gels and cream for flares rather than taking oral NSAIDs. One commentator remarked that current treatments for osteoarthritis focus on managing symptoms because there is no medication that has been proven to prevent the disease or modify its course and patients have shown a preference for efficient pain management.

One commentator highlighted the significantly higher cost of FLEXISEQ per month compared to alternative treatments. Another noted that although use of FLEXISEQ would add to costs (as an adjunctive therapy), it could reduce the cost of treating side effects if patients use it as a substitute for oral NSAIDs.