June 3, 2011 (London, United Kingdom) — Injectable collagenase significantly improved range of motion and degree of contracture in patients with Dupuytren's contracture, compared with placebo, in a pooled analysis of 2 multicenter, multinational, placebo-controlled, double-blind randomized trials. The results of the analysis were reported here at the European League Against Rheumatism (EULAR) Congress 2011.
"Injectable collagenase Clostridium histolyticum offers the first effective nonsurgical intervention for patients with this debilitating condition," noted lead author Marie-Pierre Hellio Le Graverand-Gastineau, MD, from Pfizer, in New London, Connecticut. "These findings support the use of injectable collagenase as an alternative to surgery for Dupuytren's contracture."
Dupuytren's disease is a fibroproliferative disorder that affects the palmar fascia and often leads to progressive contracture of the hand. To date, surgery has been the standard treatment. Despite successful surgery, the contractures can reemerge and progress, requiring repeat surgery to regain hand function. There is no way to identify which patients will progress after surgery.
Injectable collagenase was recently approved by the US Food and Drug Administration for adults with Dupuytren's contracture. It is injected directly into a palpable cord in the hand and disrupts the collagen, easing the contracture.
Two randomized controlled trials — CORD-I (n = 306) and CORD-II (n = 66) — showed that collagenase was more effective than placebo for patients with contracture of a metacarpophalangeal (MP) joint of 20 to 100 degrees, or contracture of a proximal interphalangeal (PIP) joint of 20 to 80 degrees.
In CORD-I, 64.0% of cords in the active-treatment group, compared with 6.8% in the placebo group, met the primary efficacy end point of reduction in total flexion contracture to 0 to 5 degrees (P < .001).
CORD-II showed that 44.4% of cords in the active-treatment group, compared with 4.8% in the placebo group, met the same primary efficacy end point (P < .001). All patients in the active-treatment group received up to 3 injections of collagenase at 30-day intervals in the contracted palpable collagen cord identified for treatment.
The pooled analysis of both trials presented here at EULAR found that 30 days after the last treatment, collagenase injections achieved a mean change from baseline in range of motion in MP joints of 40.6%, compared with 4.4% for placebo (P < .0001). Mean change in degree of contracture in MP joints was 86.7% for collagenase injections, compared with 8.1% for placebo (P < .0001).
For PIP joints, mean change in range of motion 30 days after last injection was 29.8% for collagenase and 5.1% for placebo (P < .0001). Mean change in degree of contracture for PIP joints was 63.1% for collagenase and 11.9% for placebo (P < .0001).
Collagenase injections caused few serious adverse events, compared with placebo. Common adverse events occurring in 25% of patients or more included edema (73%), contusion (70%), injection-site hemorrhage (38%), injection-site reaction (35%), and pain in extremity (35%).
A second presentation by Dr. Le Graverand-Gastineau and colleagues — of a meta-analysis — showed that collagenase injections were equally safe and effective in Dupuytren's patients who had surgery or who were surgery-naïve. This study was based on pooled data from 12 clinical trials: 3 open-label studies, 6 placebo-controlled studies, and 3 open-label extension studies. Of the total number of patients, 422 had undergone previous surgery and 660 had not.
She noted that prospective studies are needed to evaluate the long-term effects of repeated collagenase treatments for Dupuytren's contracture.
Adnan Jawad, MD, an orthopaedic surgeon currently in private practice in Riyadh, Saudi Arabia, found this study "potentially interesting." He said that he was a surgeon for 10 years in the United Kingdom, where he performed numerous surgeries for Dupuytren's contracture, before moving to Saudi Arabia, but the disease is much less common in Saudi Arabia.
"Collagenase injections may turn out to be a good alternative to surgery, but we need to know more about this treatment. For example, how many injections do most patients need? What are the long-term side effects? And can patients be retreated with collagenase or will they need surgery if they recur after collagenase? It is possible that collagenase may be a better treatment than surgery for the early stages of the disease," Dr. Jawad suggested.
European League Against Rheumatism (EULAR) Congress 2011: Abstract FRI0007. Presented May 27, 2011.
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Cite this: Nonsurgical Treatment Alleviates Dupuytren's Contracture - Medscape - Jun 03, 2011.
