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Auxilium AA4500 Trials Report.
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12/15/2007 15:06
wach 

Administrator

12/15/2007 15:06
wach 

Administrator

Re: Auxilium AA4500 Trials Report.

Hi moodanc, Dr. Denkler mentioned that in this trial no local anesthesia are allowed. With them the pain would certainly be less and they will probably be allowed when this trial is over.

Wolfgang

Quote:



... As of this moment unless there's a really, really low recurrence rate with collagenase, I'd opt for NA! When I had the NA procedure, I went back to the hotel, napped for an hour and was out shopping with no pain, bruising or other side effects.



12/15/2007 21:01
moondanc 
12/15/2007 21:01
moondanc 
Re: Auxilium AA4500 Trials Report.

Hi Wolfgang:

The research consent form says: "Local anesthesia is not recommended before the injection of study drug as an injection of anesthesia may be as painful as the injection of study drug". As far as no anesthesia allowed for 'popping" the cord the study instructions say, " A local anesthesia may not allow the doctor to provide the correct amount of pressure to 'pop' the cord."

I started with a 35-40 degree contraction, ring finger MCP (one doc measured it at 35, the other at 40) and although I can get my finger to 0-5 degrees straight, this is with a set of four exercises four times a day, lots of stretching and a night time splint which I must wear for four months.

I'm sure I'll be considered a 'success' in the trial because my finger is straight. However, I can't put my palm flat on a table and the palm of my hand is still tethered or dimpled in 5 or 6 places, the lumps are still there and my hand aches quite a bit and hurts every time I stretch it. Hopefully this will get better over the coming month but as I said in my previous post-- for me-- it just doesn't compare to NA. I'm really curious as to whether there are different outcomes for patients who have previously had OS or NA.

Quote:

--------------------------------------------------------------------------------

... Dr. Denkler mentioned that in this trial no local anesthesia are allowed. With them the pain would certainly be less and they will probably be allowed when this trial is over.

12/17/2007 18:28
bshatzer 
12/17/2007 18:28
bshatzer 
Re: Auxilium AA4500 Trials Report.

A short report today 'cause I've got my left hand covered with a giant gauze dressing and I've got to type this "hunt and peck" with my right hand only.

I had the one month follow-up appointment this morning. As I suspected, there was no improvement from my last visit - about a ten degree improvement from my starting place but no further improvement over the last two weeks.

The doctor repeated the Auxilium injections, this time more in the little finger rather than in the palm. He felt he had identified the cord which was causing the problem and though perhaps a direct injection into that might be effective. The injections into the finger seemed to be MUCH less painful than the previous set of injections - more discomforting than anything else. My next visit is tomorrow morning when, no doubt, the attempt to snap the cord will be repeated. That might be a little bit more uncomfortable - at least it was following the first set of injections.

Hopefully, this will do it this time around.

12/17/2007 18:40
moondanc 
12/17/2007 18:40
moondanc 
Re: Auxilium AA4500 Trials Report.

Hi bshatzer:

I hope it works this time for you and glad this set of injections was not as painful. I was told after my injections to keep my hand in an upright position as much as possible for the next 24 hours and to try not to move it. The reason given for this was so that the AA4500 would not "migrate" out of the injection area. I was also told not to subject my hand to any extremes of hot or cold as the AA4500 was chemically active up to 72 hours and heat or cold could stop the action. That's the reason for not being able to ice after the injection. Perhaps you might try this to see if it helps?

I'm going for my 1 week followup today. We'll see what they say because my hand hurts almost all the time if I do my exercises as instructed.

Best to you.


Quote:
A short report today 'cause I've got my left hand covered with a giant gauze dressing and I've got to type this "hunt and peck" with my right hand only.

12/17/2007 20:15
Randy_H 
12/17/2007 20:15
Randy_H 

Doc out to Lunch

moondance

Thanks for the report.

The very best data on recurrence will come from Eaton as the French data is not respected. In talking to Eaton it looks like his published data will be in the 50% plus range but certainly not near 70%. Also, to claim data on NA recurrence is suspect and then go on to say that it is much lower with Collegenase is just nuts. This is no data on Collegenase recurrence because it is too new and too few have had it. That was biased wishful thinking on the doc's part. Respected NA docs like Denkler hopes that recurrence with Collegenase will be better than NA but we just don't know yet.

Hey, I'd *love* recurrence with Collegenase to turn out even better that OS but that just isn't going to happen. The rap on NA is that it leaves the diseased tissue in place ready to create a new contraction. Well, the exact same is true with Collegenase. It does remove some tissue because it dissolves it. How much difference will that actually make? Only time and good data will tell, but that doc doesn't have his facts straight about NA and is talking out of school on Collegenase.

Edited at 17.12.07 22:18

12/17/2007 23:57
moondanc 
12/17/2007 23:57
moondanc 
Re: Auxilium AA4500 Trials Report.

Hi Randy,

I'll got through your post with my comments:

>>The very best data on recurrence will come from Eaton as the French data is not respected.

I'm curious about this, can you tell me why? Recurrence data is all over the map-- for NA and for OS.

>> In talking to Eaton it looks like his published data will be in the 50% plus range but certainly not near 70%.

I'm curious how Dr. Eaton is gathering his data. I know he used to ask all his patients to submit followup pictures. (I love Dr. Eaton and would travel to FL again for NA). Of course, for a "traditional" hand surgeon, like my study doc (who, BTW, is one of the authors of the 2002 Journal of Hand Surgery authors reporting on Phase !! trials)-- not doing NA, unless it's a "double blind" study-- it doesn't count :-).

>>Also, to claim data on NA recurrence is suspect and then go on to say that it is much lower with Collegenase is just nuts. This is no data on Collegenase recurrence because it is too new and too few have had it. That was biased wishful thinking on the doc's part. Respected NA docs like Denkler hopes that recurrence with Collegenase will be better than NA but we just don't know yet.

Actually, there is data on collagenase although you can judge for yourself, given all the twists, turns and delays of the trials, how accurate it is. Here's some data on both OS and collagenase from an abstract from Journal of Hand Surgery -- Vol. 32A No. 6 July-August 2007 --http://www.globalprovince.com/BSTC.htm#86

Open Surgery: "The authors note that “contractures may be corrected surgically by dividing the cord or performing a fasciectomy to restore function and correct the deformity.” But while some three fourths of those treated show improvement, at 32 months post surgery, there is a recurrence rate as high as 65%."

Collagenase: "In a subsequent phase III trial, long-term efficacy, tolerability and recurrence rates were further evaluated. Among their findings: “A mean of 1.4 injections was required to normalize affected joints, and clinical success was achieved in 1 to 29 days. Of 62 joints treated, 54 (87%) were clinical successes during the placebo-controlled and open-label phases. Contracture recurrence was relatively low occurring in 5 joints, 1 before 12 months, 2 at 12 months, and 2 at 24 months after treatment.”

Continued-- see next post

12/18/2007 00:16
moondanc 
12/18/2007 00:16
moondanc 
Re: Auxilium AA4500 Trials Report.


Randy said: Hey, I'd *love* recurrence with Collegenase to turn out even better that OS but that just isn't going to happen. The rap on NA is that it leaves the diseased tissue in place ready to create a new contraction. Well, the exact same is true with Collegenase. It does remove some tissue because it dissolves it. How much difference will that actually make? Only time and good data will tell, but that doc doesn't have his facts straight about NA and is talking out of school on Collegenase.

My understanding of the rap on NA is that it forms too much scar tissue. I thought one of the "pluses" of collagenase was that by dissolving the cord, scar tissue was eliminated but I was told today there is scar tissue forming from the injection of the study med and from 'breaking" the cord and that's why patients are supposed to stretch so vigorously. I was also told there aren't contraindications to stretching the hand in Dupuytren's but I know at one time I saw information on Dr. Eaton's website that said just the opposite.

It's all very confusing. How many total paitents have there been in the trials? What is/was the "Pivotal Trial'? (from the Auxilium website -"Auxilium announced on June 21, 2006 the results of a pivotal trial." (35 patients total). Initially, it was announced, " Phase 3= Total Enrollment: 216." Considering nearly 20 sites doing trials, I'm sure there must be more -- but I'm still curious how many altogether from the beginning have been in the trials.

Here's some info from "The Journal of Hand Surgery -- September 2002; volume 27, number 5"

In the September 2002 issue of The Journal of Hand Surgery, Marie A. Badalamente, PhD, Lawrence Hurst, MD, and Vincent Hentz, MD review the status of their research into using an injectable form of collagenase to treat Dupuytren's disease. Dupuytren's was first described in the 17th century, but it wasn't until the 1970s that researchers were able to identify the underlying pathogenesis of the disorder. The researchers are encouraged that the nonoperative technique they are developing may have applications beyond Dupuytren's.

Surgery has been the only effectual way to treat Dupuytren's, but surgery leads to recurrence rates from 26% to 80% and potential prolonged and extensive postoperative therapy."

So-- what's the surgery recurrence rate 26%? 80%? "as high as 65%"? as reported in Journal of Hand Surgery in August, 2007 with had 2 of the same authors as the 2002 study?

As I suspected, I'm considered a success and was told I almost certainly wouldn't need a second injection because my finger is straight. The doc told me that in the next 3 weeks the "tethered" or attached skin in my palm which is causing a good degree of pain, should dissolve. I sure hope he's right!

12/18/2007 07:00
wach 

Administrator

12/18/2007 07:00
wach 

Administrator

Recurrence after surgery

Hi moondanc, you covered the recurrence question pretty well! A few additonal comments, just to add to the confusion:

a) it depends on when you measure recurrence. As in the collagenase citation, the recurrence rates increases over time. Someone said (forgot who it was) "if you wait long enough, the recurrence rate is 100 percent". With any treatment recurrence after 1 year would be unsatisfactory. It might make sense to measure after 5 years and after 10 years. For anything beyond you will probably not find enough patients responding.

b) the definition of recurrence varies widely but sure influences the outcome. Is it a recurrence if the extension deficit eventually got worse? Or only if it got so much worse that the Tubinana grade increased? Or is it a recurrence only if the patient has to be treated again? Some even mix extension to new areas and recurrence to the treated area making data difficult to compare.

c) there is a wide variety of surgical techniques that may and probably will exhibit different recurrence rates. We are listing some of them on our page http://www.dupuytren-online.info/dupuytr...techniques.html , also trying to estimate recurrence after 5 years.

d) even with the same surgical concept the recurrence rate might depend on the skill of the surgeon. Sounds likely but difficult to prove.

e) reccurrence will probably also vary between first time treatment and treatment of already recurred cases. The latter ones will probably have a stronger diathesis. The concept of the diathesis is used to predict recurrence for specific patients. The influence of the specific patient's situation may even be stronger than the type of therapy.

It probably will need to collect many more data on all techniques to come to a statistically better assessment of recurrence. For sure the currently published data on collagenase are not sufficient. In the trials they have been quite selective in choosing their patients. Surgeons can be that picky.

Another reason why NA might come up with a similar recurrence rate as surgery: some people develop Dupuytren's after trauma. Surgery is a much bigger trauma than NA. Thus for some patients surgery might accelerate Dupuytrens. That might statistically compensate for leaving the cords in place as NA does.

Wolfgang
PS: thanks for your clarification on the use of injection of anesthesia in the current collagenase trial!

Edited at 18.12.07 09:04

12/18/2007 10:36
mcm 
12/18/2007 10:36
mcm 
steroids

Both palms (5 nodules total) were injected with kenalog 12 days ago. Right after the injection I felt increased tightness in both hands and it even seems that the contraction in the left hand has increased--although this may not be related to the injections. I've not yet noticed any positive effects. I'd be interested in knowing when I should notice positive changes. Also, I'd like to extend sincere thanks to the creators of this forum and the frequent contributors--hugely inspiring. You must realize what a help you have been to others!
mcm

12/18/2007 17:07
Randy_H 
12/18/2007 17:07
Randy_H 

Re: Auxilium AA4500 Trials Report.

moondance,

Eaton told me that even he was surprised at how unscientific the record keeping is in France. It's tends to be very anecdotal and often not specific, such as "We did NA on patient X last week and he was happy with the results." Perhaps it's not *that* bad, but certainly not close to the standards of scrutiny we have in the US. For that reason none of the American CHS were impressed by the French study(s) of safety and effectiveness of NA.

That being the case, where can we get the first good clinical data? Well, Eaton and his partner have probably done more NA than everyone else in the US combined. As you know he takes meticulous records. He told me that there was no use publishing until he had five years of recurrence data. Anything less is not publishable. From this discussion I got the strong impression that he intends to publish at some future point. While he has done over 3,000 procedures it has only been four years since he started so he has at least *two* more years before he will have a big enough data set to have anything meaningful. That's my take anyway.

By comparison the recurrence data on Collegenase is nowhere near what Eaton will eventually have. You need a much larger and older data set for statical comparison to OS. The respected studies of OS recurrence rates are a bit all over the map as you say, but *all* of them are for five years or more. So potential NA data is way ahead of Collegenase.

According to Eaton, Denkler, Kline and Roy Meals (past president of the ASSH) the professional resistance to NA has been concerns over 1) Safety and 2) Recurrence. I interviewed all of these experts personally on this exact issue. Not wanting to wait the five years, Eaton arranged to have his current data presented to last years ASSH convention. It changed a few minds but most CHSs still look to Collegenase as the future entry level procedure of choice, not NA. I think my main point to all of this is that there isn't really any medical basis for this. NA is an excellent competitive procedure to Collegenase, especially considering cost. There is no definitive data to refute this as yet.

But, if Collegenase turns out to somehow really have significantly lower recreance rates, then great. You just don't have the facts to claim that.

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