Collagenase Treatment of Dupuytren's
(First posted January 1, 2010 Last updated January 30, 2015)
Collagenase: A New Option
Background and Regulatory Issues
NOTE: In February of 2014, the FDA sent out a letter to all surgeons entitled
|
NOTE: In January of 2015, the FDA sent out a new letter entitle "Important Drug Warning."
Two researchers (Marie Badalamente, PhD, and Larry Hurst, MD) have been investigating for many years the use of an enzyme that digests the collage fibers in Dupuytren's contractures. Based on three different levels of FDA-approved patient experimental studies of a brand of collagenase derived from Clostridia bacteria called Xiaflex, the FDA advisory panel recommended approval for marketing on September 16, 2009. The FDA approved the product for marketing on February 2, 2010, and it was released later that year. The price (the drug costs about $3250 per injection and more than one is needed) is considerable. It is also important that both physicians and patients realize that the FDA never approves a drug or device for use, or approves its use. It only approves the marketing of the product. The FDA was empowered by Congress to regulate marketing, not the medical profession. Whether or not the drug or device is medically indicated is a medical decision made by a doctor. There are many drugs and devices on the market that are not safe to be used. This may seem odd, but you need to understand the enabling legislation pass by Congress. I am on the FDA Advisory Panel and have learn a great deal about the workings of the FDA by my years of service on the Panel.
How It Works
The new drug is a collagenase, which means it is an enzyme that facilitates the desolving of collagen. The fundamental concept in treating Dupuytren's with collagenase is to inject the enzyme into the Duputyren's cords (which are thick collagen ropes), weaken them by partly dissolving the collagen (Type I collagen; there are at least four major types of collagen and many more less common types), then stretching the cord and rupturing it. The advantage is that no surgery would be needed and the recovery should be much faster than in open fasciectomy. One disadvantage is that no Dupuytren's tissue is removed, another is that the only contracture that is relieved is that which can be stretched and ruptured by extending the finger. The nodules and skin deformities are not removed. The potential complications of the injections are skin inflammation and soreness (essentially 100% of the patients in the studies had this complication), but this is minor. Rarer potential complications are that the enzyme will dissolve the collagen in the tendon (also Type I), or in the adjacent nerve or artery (other collagen types, with a lesser sensitivity to the enzyme but still sensitive to it).
One big unknown is the rate of recurrence (Duputyren's contractures occuring in the same tissues) or extension (Dupuytren's contractures occuring in adjacent tissues that previous had the gene for Dupuytren's but had not yet gotten involved). According to one study * supported by the company the markets the enzyme, the recurrence of contracture in all joints at one year is 3%, two years is 19.6%, and at three years is 35%. However, PIP joints recur faster than MP joints, with rates of 6%, 33%, and 56%.
Now, after several years on the market, it would appear that the recurrence rate with the enzyme is longer than for needle aponeurotomy and much faster than with open fasciectomy; it can be estimated that recurrence may average at about 3-4 years. An estimate of average return after needle aponeurotomy might be 2-3 years, and for open fasciectomy might be 8-10 years. Please discuss this with me during your appointment.
Another possible complication is the effect of the inflammatory reaction to the enzyme causing more rapid recurrence or more extensive extension, or both. Only further time will tell the answers to these important questions. I have personally discussed the studies with Dr. Badalamente (most recently in September of 2009) and with surgeons who were involved in the FDA-supervised experimental use of the enzyme on patients.
I personally have Duputyren's in both of my hands, so I am not an idle observer: I am a Duputyren's patient, such as yourself. At this time (August 4, 2011), I do not want to have such an experimental procedure done on my hands. There are too many unknowns for me. Many promising new medical treatments work great and become the new standards, many new promising treatments, after they have been tried by many doctors and there are many years of experience with it, are found to be either only partially effective or even can be found to actually be harmful. On this particular treatment, I want more outcome data before I recommend it.
The question is not CAN it be done, but HOW DOES IT COMPARE to other procedures. I have been tracking how well my open fasciectomy patients do, and have discussed it with the hand therapy unit that treats not only my patients, but also patients from doctors all over the Marin and San Francisco areas. My patients have a quicker recovery and less pain than anyone else's patients. We think this is due to my post-operative pain program (remember, I am a member of the International Association for the Study of Pain and have been doing pain research for 20 years). If patients don't hurt, they can move their fingers. If they move their fingers, they do not get stiff and can return to activites earlier. In addition, all of my sutures are inside the skin, just like a movie's star's facelift. With no sutures to retard recovery, patients do better. Because of the rapid return to activities, there is less reason to do either needle aponeurotomy or enzyme injection, as the downside of my fasciectomies is so little.
Not everyone does well after a Dupuytren's procedure, no matter what type is chosen. Medical science does not know why, but some patients have what is called a Duputyren's flare. They get very swollen, red, and stiff, and their Duputyren's contractures come back quickly, often in months. So far, we cannot predict who will get this, but it represents less than 4% of patients.
BOTTOM LINE: If I needed treatment of my Dupuytren's today (I do not, as I have full extension and flexion of all of my fingers), I personally would have an open fasciectomy. That is why I recommend it to my patients, over either needle aponeurotomy or enzyme injection.
* backup here
