Dupuytren's disease is a fixed flexion contracture deformity of the hand currently treated by surgical fasciectomy of the collagenous cords responsible for the finger joint contractures. Our prior Phase 2 controlled, clinical trials have clearly indicated safety and efficacy of collagenase injection therapy as an alternative to surgery. The purpose of this Phase 3 study was to further test collagenase injection as a nonsurgical treatment for Dupuytren's disease.
Methods 35 patients were enrolled in the random, placebo, double-blind control protocol allowing for an assignment to 0.58 mg collagenase or saline placebo, maximum three injections. At this time, the control treatment code may not be unmasked. However, patients had the option to enroll in an additional protocol either for treatment failure or because they had additional contracted joints of the same or opposite hand. The second protocol allowed for a maximum five open label, 0.58 mg, collagenase injections, given at one month intervals. Seventeen patients were treated in the open label protocol, 12 male and 5 female, mean age 62 years, 12 metacarpophalangeal (MP) joints and 16 proximal interphalangeal (PIP) joints. The initial mean MP and PIP joint contractures were 45° and 43°, respectively. Collagenase injections, 0.58 mg, were to the collagenous cords, using an insulin syringe, 0.25 mL for MP joints and 0.20 mL for PIP joints. Patients were seen in serial follow up at 1, 7, 14 and 30 days, and 2, 3, 6, 9 and 12 months.
Results 92% of the MP joints and 75% of the PIP joints treated achieved full, normal finger extension (0°), most within one week of one collagenase injection. Results were sustained in the longer term, mean follow-up, 125 days for MP joints and 107 days for PIP joints. There was no loss of normal finger flexion, or normal grip strength. Adverse events included pain associated with “cord rupture,” hand edema and palmar ecchymosis. These resolved without problems in 7-14 days.
Conclusions Collagenase injection therapy for Dupuytren's disease continues to show clear merit in Phase 3 clinical trials as a safe and effective alternative to surgical fasciectomy. National, multicenter, Phase 3 study of this promising method will begin in the next several months. This study was supported by the FDA (Grant 001437), the NIH (GCRC-M01RR10710) and the Biospecifics Technologies Corp.