Features
Speed of response
Patients’ response times to toxins were usually measured as starting one week after injection. But in practice patients have responded much more quickly, and researchers have proven that to be the case in large and smaller studies, writes Professor Andy Pickett
The growing use of non-surgical aesthetic procedures is phenomenal. There are no exact figures, because they are not recorded in most countries. The annual survey by the American Society of Plastic Surgeons reports 5.4 million botulinum toxin (BoNT) procedures in 2010. This is the tally for only one society’s members in one country. The figure must be at least twice this for worldwide use of BoNT alone. South America, Asia and Europe are equally important markets as the US, and BoNT for aesthetic treatments is growing, as are dermal filler sales.
There is a similar growth in discerning patients. More patients want to know details of their procedures, the products and their clinicians’ experience. Although much non-surgical treatment is repeat business from satisfied customers, word-of-mouth recommendation is important in spreading growth. This does not mean patients are less demanding.
Two key questions of modern BoNT treatment foremost in patients’ and doctors’ minds are how fast will the product work and how long will the effects last?
Until 2009, no one had really looked at how fast a BoNT product worked after injection. There are uncountable publications on both the aesthetic and medical uses of BoNT—even in controlled clinical trials—that have the first study time point as seven days after injection. Apparently, the assumption was that nothing would be seen before seven days.
But in 2009 our knowledge changed significantly as new data appeared from the US trials of Dysport looking at what happened before seven days1.
The results were remarkable. The data clearly showed that 50% of patients were responding by 2.5 days after injection. As important, this effect was repeated for the five cycles of treatment in the study. This was the first time that such data became available. This was a large study: 1200 patients were enrolled, receiving at least one cycle of BoNT.
It wasn’t until 2011 that similar data appeared for Botox2, almost saying this important aspect of treatment had not been systematically studied for the product before. The study published was for only 45 patients, a small data-set considering Botox’s widespread use. In fact, speakers for the manufacturer were seen at international aesthetic meetings presenting pictures of their early patient records to try to persuade the audience this was old news.
But this remarkable finding—against all the old beliefs of BoNT action—served to really get people interested in finding out what was a real time for onset of action. Many clinicians reported anecdotally that many of their patients felt they were seeing (and feeling) an effect a few hours after injection.
Remarkable data from Mark Nestor and Glynis Ablon, based in the US, show a head-to-head comparison of Botox and Dysport that looks at the time of action onset after injection into the frontalis3. Five injection points were used, one product on each side of the patient’s forehead, and effects measured on a four-point frontalis rating scale. For the comparison in 20 patients, 25 units of Dysport were injected (five units per injection point) and 10 units of Botox (two units per injection point).
Their findings are summarised in Table 1. Overall, an initial onset for Dysport was found in 12 hours, but took 48 hours for Botox. Complete onset for Dysport occurred in 72 hours and for Botox in 120 hours, according to the rating scale. The differences were highly significant. These data showed, for the first time, a clear difference in onset of action between the two main BoNT-A products.
Why would such a difference occur? After all, the active component is the same in both products, BoNT-A neurotoxin. We do not have an answer yet from BoNT science and any potential reason would be pure speculation at this time. We already have too much speculation and myths about the BoNT products, so now is not the time to add another subject. But the difference seems real.
So how about the duration of action? Are there any product differences there?
Nestor and Ablon have published, simultaneously to their work on onset of action, a direct head-to-head comparison of duration of action of the two main products, using the same doses and sites of injection as before4. This is probably the same patient population but also looking at duration of action.
Again their findings were clear (Table 2). The mean duration of different effects, now using two ways of measurement, were longer for Dysport in every case compared with Botox. A product difference was once more identified.
Other studies, on the treatment of glabellar lines in particular, have not shown such differences in duration of action between the main products (summarised by Rzany and Nast5). The strong and short corrugator and procerus muscles treated for glabellar lines are, however, very different from the wide, flat frontalis muscle studies by Nestor and Ablon in detail, so perhaps differences in responses might be expected?
The studies summarised by Rzany and Nast show that both products are capable of producing continuing effects out to 120 days after injection in about 30% of patients. Other studies on Dysport have looked as far out as six months after injection and found about 10% of patients still have a good effect6. Equivalent data exist for Botox.
What we can now say, with substantial supporting clinical evidence, is that BoNT products give a rapid onset of action, in some cases within half a day, and have a long duration of effect, perhaps as long as six months. There do seem to be product differences and we cannot yet explain these, but we wait now, once again, for the science to catch up with the clinical practice of using BoNT, to give us that next stage of explanation. This has been a permanent feature of BoNT use, in any indication.
Clinical uses have always outpaced the science. We now hope the scientists find the key to two of the most important aspects of BoNT aesthetic use, supplying the next answers for the patients.
Professor Andy Pickett is director and founder of Toxin Science Ltd. He previously worked for Ipsen Biopharm and has been in the toxin field for 23 years
