Collagen as a clinical target: nonoperative treatment of Dupuytren's disease

Abstract

The cellular events leading to abnormal synthesis of collagen are important to our understanding of pathologic processes leading to impaired joint function. The contracture of Dupuytren's disease is a notable example. In a series of controlled phase-2 clinical trials, excessive collagen deposition in Dupuytren's disease has been targeted by a unique nonoperative method using enzyme (Clostridial collagenase) injection therapy to lyse and rupture finger cords causing metacarpophalangeal and/or proximal interphalangeal joint contractures. Forty-nine patients were treated in a random, placebo-controlled trial of one dose of collagenase versus placebo at one center. Subsequently 80 patients were treated in a random, placebo-controlled, dose-response study of collagenase at 2 test centers. The results of these studies indicate that nonoperative collagenase injection therapy for Dupuytren's disease is both a safe and effective method of treating this disorder in the majority of patients as an alternative to surgical fasciectomy. Phase-3 efficacy trials are now being planned to further develop and test this method under Food and Drug Administration regulatory guidelines. The findings of our study may lead to simpler and less invasive nonoperative treatments of joint limitation in which collagen plays a major pathologic role.