BERLIN – Medical therapy might prove to be the preferred approach for treating patients with early-stage Dupuytren’s contracture, suggest the findings of a small retrospective study.
Injection of collagenase Clostridium histolyticum in patients with early-stage Dupuytren’s contracture resulted in significantly better clinical outcomes than those that were seen in patients with advanced disease. Collagenase C. histolyticum (Xiaflex) injections are generally given only after patients with Dupuytren’s contracture develop fixed-flexion contracture angles of 30 degrees or more.
The retrospective study suggests a new treatment paradigm: The early injection of palpable cords with lesser fixed-flexion contracture angles results in near normal correction, bringing improvement that’s significantly greater than that achieved with delayed therapy, according to Dr. Clayton A. Peimer, an orthopedic surgeon at Michigan State University, East Lansing.
This is off-label therapy. At present, Xiaflex is approved in the United States and Europe under more restrictive conditions (injection of only a single palpable cord at a time, with a 4-week hiatus before either a repeat injection or an injection of another affected cord).
The finding warrants confirmation in prospective longitudinal studies aimed at determining whether collagenase injections into early-stage joints slows progression of Dupuytren’s contracture and improves upon the high contracture recurrence rate that follows surgical release, he added.
In a separate Australian study presented at the annual European Congress of Rheumatology, Dr. David Gilpin of the Brisbane (Queensland) Hand and Upper Limb Clinic reported that concurrent injections of collagenase C. histolyticum into two affected palpable cords in the same hand proved safe, effective, and well tolerated.
The advantages of being able to safely treat multiple contractures at the same time include shortened recovery times, fewer office visits for patients, and more efficient use of physicians’ time, noted Dr. Gilpin.
His study included 12 patients with three or more fixed-flexion contractures of 20% or greater in the proximal interphalangeal (PIP) and/or metacarpophalangeal (MP) joints on the same hand. The participants initially received a single collagenase injection in one palpable cord, followed roughly 24 hours later by the standard finger extension procedure that breaks the now-weakened cord. After 30 days, the patients received two injections into two different palpable cords on the same hand, followed by finger extension procedures the next day.
The first injection resulted in a mean 81% reduction in the degree of fixed-flexion contracture in treated MP joints, and a 66% decrease in PIP joints. The subsequent two concurrent injections of other affected cords showed near identical effectiveness (mean reduction in fixed-flexion contractures, 80% in MP and 63% in PIP joints).
Blood samples that were obtained 24 hours after the dual injections showed no detectable systemic levels of the biologic agent.
Not surprisingly, several treatment-related adverse events were more common when patients received two injections rather than one. These included injection site pain or discomfort, skin discoloration, itching, and blood blisters.
Dr. Peimer reviewed the charts of 302 patients with Dupuytren’s contracture who were treated with collagenase injections at 10 U.S. community and academic practices. Of affected joints, 20% were treated at an early stage (defined as a fixed-flexion contracture angle of 30 degrees or less). Their mean initial fixed-flexion contracture angle was 25 degrees, improving to 3.8 degrees after treatment. In contrast, the mean baseline fixed-flexion contracture angle in patients with advanced disease was 58 degrees, with an improvement to 14 degrees following collagenase treatment. No serious treatment-related adverse events occurred.
Dupuytren’s contracture is the result of a usually painless progressive thickening and shortening of the palmar fascia. This leads to curling of the fingers and impaired hand function. The most common surgical treatment, limited fasciectomy, can result in complications including digital nerve injury, hematoma, and complex regional pain syndrome. Xiaflex was approved in the United States in 2010 as the first nonsurgical treatment for Dupuytren’s contracture. European approval followed the next year.
The studies were sponsored by Auxillium Pharmaceuticals, which markets Xiaflex. Dr. Peimer and Dr. Gilpin were paid by the company for their research, and Dr. Gilpin owns stock in Auxillium.