Surgical risks prompt search for nonsurgical alternative

In spite of high complication and recurrence rates, surgical fasciectomy continues to be the treatment of choice for Dupuytren’s disease, although that may start to change based on the results of an ongoing series of trials examining the efficacy of collagenase for the treatment of Dupuytren’s. Presenting 8-year follow-up results of a Phase II trial at the annual meeting of the American Society for Surgery of the Hand, Andrew J. Watt, MD, stated that enzymatic fasciotomy with collagenase appears to be a safe and efficacious treatment, offering reliable initial reduction in joint contracture.

Dupuytren’s, a progressive disease of the palmar digital fascial structures, is characterized by nodular thickening and subsequent contracture. The degree of hand disability is related to the contracture of the metacarpophalangeal (MCP) joints and the proximal interphalangeal (PIP) joints. Previous studies looking at surgical fasciectomy have reported complication rates ranging from 17 percent to 29 percent. Hematoma and skin necrosis are the most common complications, and nerve injury occurs in up to 9.6 percent of cases. The disease recurrence rates are also high, with studies finding recurrence rates of 41 percent to 54 percent at 5 years.

“Although the initial operations are challenging, revision or secondary operations are even more challenging and have even higher rates of complication,” said Dr. Watt. “This continues to lead to the desire for a nonsurgical treatment modality.”

Studies into enzymatic fasciotomy dating back to the mid-1960s reported favorable initial results, but concluded that recurrence rates were similar between surgical and nonsurgical treatments. They also raised concerns about the possibility of tendon rupture and neurovascular injury due to nonspecific enzymatic degradation. Collagenase offers an advantage over traditional enzymatic fasciotomy by targeting only type I and type III collagen.

MCP patients fare well
The original Phase II trial looked at 129 patients, randomized to determine dose-response, efficacy, and safety. In the 8-year follow-up, eight patients who had been randomized to experimental groups were available for examination by an independent examiner, who was blinded as to which finger was treated as part of the original trial. Patients also completed a questionnaire related to disease recurrence and progression.

Six of the eight patients had received a collagenase injection for MCP joint contracture, and two had been treated for PIP joint contracture. The MCP patients had an average 58-degree contracture prior to the injection and reliably achieved extension of 8 degrees, which was maintained at 1 year within a standard of error. At 8 years, however, four of the six MCP patients experienced some degree of contracture recurrence (average 22 degrees).

“The results for the two patients with PIP joint contracture were less promising,” said Dr. Watt. “Although the treatment initially relieved the contracture, both patients experienced a recurrence by 8 years—one to 30 degrees and the other to 90 degrees.”

On a subjective basis, 60 percent of the follow-up patients felt that the injection was a clinical success, and 88 percent stated that they would pursue further injections if available.

A nonsurgical future?
“The key to success for this treatment is the careful placement of just a few drops (0.2 mL ) of the liquid,” explained Vincent R. Hentz, MD, who took part in both the original study and the follow-up. “You have to carefully inject the collagenase into the cord so that it performs its action only on the cord. A good candidate—an absolute indication—is a patient with a cord that the surgeon can feel with his or her fingers and knows is the cord causing the joint contracture. (Fig. 1)”

“One of the hallmarks of Dupuytren’s disease is that we don’t have a cure,” said Dr. Hentz. “As hand surgeons, we treat the sequelae of the disease, which is contracted fingers. We know that over time, the recurrence rate is high or the disease progresses—it appears in other areas of the hand. So we expect that most patients we treat will eventually develop new disease—disease in another area of the hand—or recontracture of a treated finger. What we don’t know from our collagenase work is what this recurrence rate is. We have initiated a prospective, randomized Phase-3 trial and have published initial results. We will be following these patients for the next 5 years to see the progression of the disease and determine a recurrence rate.”

Dr. Hentz pointed out that future research could examine the effect of early collagenase treatment. Generally, surgeons have waited until significant contracture has developed before recommending surgical fasciectomy. If collagenase injections are found to be safe and easier on the patient, this nonsurgical treatment may offer potential relief to some patients who aren’t currently candidates for surgery.

In addition to Drs. Watt and Hentz, Catherine Curtin, MD, was a coauthor for “Collagenase Injection as Nonsurgical Treatment of Dupuytren’s Disease: 8-Year Follow-up.” Funding for an ongoing Phase III clinical trial of collagenase and research or institutional support received from Auxilium.

Peter Pollack is a staff writer for AAOS Now. He can be reached at ppollack@aaos.org

Read the Phase 3 trial report on treating Dupuytren’s contracture