Correspondence

Injectable Collagenase Clostridium Histolyticum for Dupuytren's Contracture

N Engl J Med 2009; 361:2578-2580December 24, 2009

Article

To the Editor:

Hurst et al. (Sept. 3 issue)1 report on the significant therapeutic effect of injectable collagenase clostridium histolyticum in patients with Dupuytren's contracture. They also report two cases of tendon rupture. We are concerned about the injection depth. In this study, the collagenase clostridium histolyticum was injected directly into the fibrotic cord. It is very difficult to control the depth of injection to protect the normal tendon. Once the drug is injected into the tendon lying beneath the cord, decomposition of collagen in the tendon may occur and the tendon could rupture when the joint is manipulated.

Peng Zhang, Ph.D.
Ling Qin, Ph.D.
Chinese University of Hong Kong, Hong Kong, China
superzhangpeng@sina.com

No potential conflict of interest relevant to this letter was reported.

1 References

1
Hurst LC, Badalamente MA, Hentz VR, et al. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med 2009;361:968-979
Full Text | Web of Science | Medline

To the Editor:

The recurrence rate is a measure of successful treatment of Dupuytren's disease and correlates proportionally with the percentage of excised Dupuytren's tissue and the extent of the intervention.1 The effect of collagenase clostridium histolyticum can be considered to be similar to that of mechanical intersection of Dupuytren's tissue by means of percutaneous needle aponeurotomy.2 The subsequent manual manipulation leads quite logically to an increase in range of motion in both the metacarpophalangeal and proximal interphalangeal joints. The value of the new minimally invasive technique described by Hurst et al. has to be proved in a long-term follow-up study with a focus on the recurrence rate, and therefore the findings of this study cannot be seen yet as evidence for the use of this procedure in clinical practice.

Lukas A. Holzer
Gerold Holzer, M.D., Ph.D.
Medical University of Vienna, Vienna, Austria
gerold.holzer@meduniwien.ac.at

No potential conflict of interest relevant to this letter was reported.

2 References

1
Rayan GM. Dupuytren disease: anatomy, pathology, presentation, and treatment. J Bone Joint Surg Am 2007;89:189-198
CrossRef | Web of Science | Medline

2
van Rijssen AL, Werker PM. Percutaneous needle fasciotomy in Dupuytren's disease. J Hand Surg Br 2006;31:498-501
CrossRef | Medline

Author/Editor Response

Among the 444 injections of collagenase clostridium histolyticum administered in 308 patients in the Collagenase Option for Reduction of Dupuytren's (CORD) I study, two tendon ruptures were reported. Both occurred in the proximal interphalangeal joint of the fifth finger and involved the flexor digitorum profundus and flexor digitorum superficialis. After the first tendon rupture, the injection technique was modified, and the investigators were instructed to inject the cords of the fifth finger more proximally, near the first flexion crease, avoiding the area immediately palmar to the proximal interphalangeal joint at the second flexion crease.

When injecting cords that affect the proximal interphalangeal joints, the needle should be placed into the cord in a horizontal plane, not vertically. The distance between the skin and the flexor tendon averages 7 mm at the metacarpophalangeal joint and 4 mm at the proximal interphalangeal joint,1 and the 27-gauge needle bevel is approximately 1.25 mm. This information should allow clinicians to safely inject Dupuytren's cords without injecting flexor tendons. Stabilizing the needle while pushing the plunger should also help in preventing injection through the cord.

The Supplementary Appendix to our article contains details of the injection and manipulation techniques used in CORD I. As of this writing, more than 2600 collagenase injections have been administered in more than 1000 patients. Three tendon ruptures have occurred (two in CORD I and one in a pharmacokinetic study), for an overall incidence of three cases of tendon rupture per 2600 injections (0.1%), which is similar to reports of the incidence of injury to the flexor tendon during surgery (0.2%).2

Determining the true prevalence of recurrence after surgical treatment of Dupuytren's contracture on the basis of the literature is difficult because of variations in the definition of recurrence, duration of follow-up, study design, and patient populations. Currently, 1-year CORD I data on recurrence after treatment with collagenase clostridium histolyticum are available. Recurrence, defined as an increase in joint contracture to at least 20 degrees in the presence of a palpable cord, was evaluated for up to 12 months in 830 joints in patients who were successfully treated (i.e., a reduction in contracture to ≤5 degrees) during the entire phase 3 clinical program. After adjusting for the various follow-up periods, the projected mean (±SD) rate of recurrence at 12 months was 6.7±1.7% based on the Kaplan–Meier estimate.3

Lawrence C. Hurst, M.D.
Marie Badalamente, Ph.D.
State University of New York at Stony Brook, Stony Brook, NY
lhurst@notes.cc.sunysb.edu

Theodore Smith, Ph.D.
Auxilium Pharmaceuticals, Malvern, PA

Since publication of their article, the authors report no further potential conflict of interest.

3 References

1
Hurst LC, Badalamente MA. Nonoperative treatment of Dupuytren's disease. Hand Clin 1999;15:97-107
Web of Science | Medline

2
Loos B, Puschkin V, Horch RE. 50 Years experience with Dupuytren's contracture in the Erlangen University Hospital -- a retrospective analysis of 2919 operated hands from 1956 to 2006. BMC Musculoskelet Disord 2007;8:60-60
CrossRef | Web of Science | Medline

3
Briefing information for the September 16, 2009, meeting of the Arthritis Drug Advisory Committee. Silver Spring, MD: Food and Drug Administration. (Accessed December 3, 2009, at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisDrugsAdvisoryCommittee/ucm182012.htm.)

Citing Articles (1)