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Clinical lead, Professor David Warwick
Collagenase for Dupuytren’s Contracture

It is not often in orthopaedic surgery that something so new and different comes along that it revolutionises treatment- hip replacement and arthroscopy for example.  But the uncomfortable truth for us surgeons is that it will be biological treatment rather than mechanical treatments that will make the biggest change. How many of us have seen our rheumatology practice implode since the new anti-rheumatic drugs arrived? I suspect that one day, gene therapy will take away our osteoarthritis practice as well.

Just over two years ago, Collagenase Clostridium Histiolyticum (Xiapex) was approved in Europe for use in Dupuytren’s contracture. It was developed in a laboratory then clinical studies over many years in Stonybrook Hospital in New York.1  Phase III trials proved it to be efficacious and safe2,3 and so the drug was introduced into clinical practice. Subsequent studies have confirmed its efficacy.4  A follow-up study5 has shown the recurrence rate, at 30% for MP contractures and 50% for PIP contractures, to be somewhere between that expected for surgery (with its longer recovery and higher complication rate) and needle fasciotomy (with its cheapness but risk to digital nerves).

Patient satisfaction is high since the correction is immediate and recovery to normal function is prompt.  At least 10% of patients have a skin split or blood blister but these do not seem to slow recovery and resolve in a shorter time than one would expect a surgical wound to heal. There is a theoretical risk of a catastrophic allergic reaction but this has not yet been reported; quite a few patients though have hand swelling or even axillary pain.

Surgeons need not fear that the drug will eradicate their Dupuytren’s practice.  Because CCH will dissolve the collagen in the flexor tendon, a misplaced injection would be a catastrophe. For this reason the drug can only be used by those thoroughly familiar with the anatomy of the hand which means hand surgeons.  Also, not all Dupuytren’s is suitable- diffuse disease cannot be injected as one needs a discrete cord to inject then snap.  One can only inject one digit at a time (according to the present licence although that might change); for those with multiple digits the cost-effectiveness in a financially strained system for several injections at £800 each rather than one operation is questionable.  It should not be used under a previous graft lest the graft lifts away.

So for the time being, we hand surgeons will still have a job and we can still treat Dupuytren’s Disease. Well, that is until the gene therapists stop it from developing at all……….

Professor David Warwick, Hand Surgeon, University Hospital Southampton, UK
August 2014

 

References

1. Badalamente MA, Hurst LC. Efficacy and safety of injectable mixed collagenase subtypes in the treatment of Dupuytren's contracture. J Hand Surg Am 2007;32-A:767-74.
2. Hurst LC, Badalamente MA, Hentz VR, et al. 
font-family:"Arial","sans-serif"">Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med 2009;361:968-79.
3. Gilpin D, Coleman S, Hall S, et al. 
font-family:"Arial","sans-serif"">Injectable collagenase color:blue;text-decoration:none;text-underline:none"> clostridium histolyticum: a new nonsurgical treatment for Dupuytren's contracture. J Hand Surg Am 2010;35-A:2027-38.
4. Witthaut J, Jones G, Skrepnik N, Kushner H, Houston A, Lindau TR. 
Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: short-term results from 2 open-label studies. J Hand Surg Am 2013;38-A:2-11.
5. Peimer C, McGoldrick C, Fiore G. 
Nonsurgical treatment of Dupuytren's contracture: 1-year US post-marketing safety data for collagenase clostridium histolyticum. Hand (N Y) 2012;7:14