Flexiseq

FLEXISEQ is a gel containing very small particles but no drug. It's used for osteoarthritis, particularly of the knee.

We asked an independent panel of experts in rheumatology, complementary medicines and nutrition to search and evaluate evidence on the safety and effectiveness of FLEXISEQ. Their assessment showed that from the scientific studies available we don’t yet understand how it works or whether it’s more effective than a completely inactive gel rubbed on to the knee.

We also don’t yet have enough information to say whether there any important safety issues, given the fairly small number of patients studied in the published clinical trials of FLEXISEQ to date.

FLEXISEQ was first developed to carry drugs directly into the knee in order to ease the symptoms of osteoarthritis. It was then used as a comparator for studies in which some preparations were carrying active drug to the knee joint. Trial results have suggested that the particles may have positive effects when they don’t contain any drug.

The manufacturers of FLEXISEQ claim that as the gel begins to dry, the very small particles seek out water and move through the skin into the knee joint. They claim that these particles attach themselves to cartilage, which helps to ‘lubricate’ the joint, reducing joint stiffness and helping with pain.

Other possible ways that it might work are that the particles absorb inflammatory chemicals or break down into chemicals which reduce inflammation and pain.

There haven’t been any scientific studies reported which have directly examined these theories, so at the moment we don’t understand how it might work.

In the trials of FLEXISEQ, only a small proportion of participants using the gel reported side-effects. These were nearly always affecting the skin such as:

• irritation
• redness
• a rash.

Only a fairly small number of participants have used FLEXISEQ in randomised controlled trials. Treatment during these trials lasted for just a few weeks, so we don’t know whether longer-term use is linked with safety issues.

We’ll have a better understanding of any safety issues when we have data from longer-term studies with more participants.

As FLEXISEQ doesn’t include any drug, it’s not expected that it would interact with other drugs. However, we don’t have enough data at the moment to be confident of this.

Only a small number of trials have been published on FLEXISEQ. They have all involved a small group of investigators, several of whom have financial relationships with the companies involved in developing the device.

This doesn’t make the results invalid but it’s important to take into account when thinking about the evidence.

There have been four randomised controlled trials conducted among participants with osteoarthritis of the knee. None of these have been reported by investigators independent of the companies developing the device.

Trial 1 (2007)

In the first trial of 397 particpants treated for six weeks, FLEXISEQ was less effective than a gel containing ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) and celecoxib tablets (a NSAID used to treat mild to moderate osteoarthritis symptoms).

The following percentages of participants rated their response as ‘good’ or ‘excellent’:

• ketoprofen gel = 46%.
• celecoxib tablets = 39%
• FLEXISEQ = 28%

Trial 2 (2013)

In the second trial, 1,395 participants were treated for 12 weeks.

• FLEXISEQ had similar effectiveness on pain, function and stiffness as a gel containing ketoprofen and celecoxib tablets, and it was more effective than a placebo tablet.
• Pain reduction was between 38–41% for all the treatments, compared to 29% reduction in those taking inactive tablets.

If this study had included a truly inactive gel as comparison it would have allowed us to be more certain whether the difference was real or not.

Trial 3 (2013)

866 participants were treated for 12 weeks:

Participants using gels containing different doses of ketoprofen were all more likely to improve than persons using FLEXISEQ (using an internationally accepted definition of “improvement”).

Most participants using FLEXISEQ did improve.

Trial 4 (2013)

FLEXISEQ was compared to a gel with ketoprofen in 555 participants treated for 12 weeks.

• Participants using keoprofen gel were less likely to improve compared to those using FLEXISEQ.
• Those using FLEXISEQ reported a 40–45% decrease in pain, function and stiffness.