Satisfactory Recurrence Rates for Collagenase in Hand Contractures

Jill Stein

February 23, 2011

February 23, 2011 (San Diego, California) — Collagenase injections are associated with overall satisfactory rates of recontracture in patients with Dupuytren's disease of the hand, according to results presented here at the American Academy of Orthopaedic Surgeons 2011 Annual Meeting.

"The data from both single-center and multicenter studies show that, at 2- to 5-year follow-up, the recurrence rates after collagenase treatment are good with respect to the metacarpophalangeal [MP] joint, and comparable to published studies indicating a higher surgical recurrence in the proximal interphalangeal [PIP] joint," said Marie A. Badalamente, PhD, from the Department of Orthopaedics at the State University of New York at Stony Brook.

The single-center study examined 35 patients who were followed for a mean of 3.9 years after successful treatment with 0.58 mg collagenase injection(s). Of these, 15 patients (43%) achieved at least 5 years og follow-up.

The multicenter analysis consisted of 474 patients followed for 2 years after initial successful treatment.

Standard Treatment Problematic

Dupuytren's contracture is a progressive genetic disorder of pathologic collagen production and deposition that eventually leads to flexion joint contractures that can severely limit hand function and cause hand deformity.

The condition has historically been treated by surgical fasciectomy or percutaneous fasciotomy. Contracture recurrence rates have ranged from 27% to 80% after surgical fasciectomy, and can be highest in PIP joints. Contracture recurrence rates of 65% to 85% have been reported after percutaneous fasciotomy.

Complication rates after surgery range from 0.2% for tendon ruptures to about 10.0% for infections, digital tendon, and arterial injuries.

Several nonsurgical treatments have been tested, including radiotherapy, physical therapy, corticosteroid injections, topical vitamin A and E, ultrasonic therapy, and gamma interferon injections, but all have been found to be ineffective, Dr. Badalamente noted.

Collagenase for intralesional injections was approved for the treatment of adult patients with Dupuytren's contracture with a palpable cord in February 2010. Collagenase is injected in the affected cord, and the treated joint is then manipulated to facilitate cord rupture. Collagenase lyses and disrupts the collagen cord, leading to a decrease in contracture and an improvement in the range of motion of the affected joints.

Unlike with surgical fasciectomy or percutaneous fasciotomy, hand therapy is not required after collagenase injections.

Durable Results Seen With Collagenase

At baseline, study participants in both the single-center and multicenter analyses had a fixed flexion deformity of at least 20 degrees of the MP or PIP joints in at least 1 finger.

Clinical success was defined as 0 to 5 degrees of normal extension.

Of the 28 MP joints that achieved clinical success with collagenase injections in the single-center study at a mean follow-up of 3.9 years, there were 4 recurrences. A recurrence was defined as a joint contracture of at least 20 degrees; all measurements were obtained using a digital goniometer.

Of the 26 PIP joints that achieved initial clinical success, there were 6 recurrences.

"Thus, the recurrence rates in the single-center study were 14% for MP joints and 23% for PIP joints," Dr. Badalamente said.

Two-year follow-up in 474 patients with 618 joints that were initially successfully treated in phase 3 trials demonstrated a 19.3% recurrence rate in all joints. This included a 13.6% recurrence rate for MP joint contractures and a 34.1% recurrence rate for PIP joint contracture.

Dr. Badalamente emphasized that surgery, needle fasciotomy, or collagenase cannot cure Dupuytren's contracture. However, the less invasive nature of the collagenase injection, a "relatively low" recurrence rate, and a high rate of patient satisfaction make collagenase an appealing treatment option.

She added that she and her colleagues plan to assess recurrence annually for 5 years.

"This treatment offers satisfactory results with a very acceptable risk/benefit ratio; there is a recurrence rate there that appears to be a 'no bridges burned' situation that will allow for further treatment if needed over time," said Steven A. Stuchin, MD, site chief of the Department of Orthopedic Surgery at NYU Hospital for Joint Diseases in New York City. "Cost, limitation of the number of injection sites at any one event, and the risks of tendon rupture are the mitigating factors."

Dr. Badalamente reports receiving royalties from Biospecifics Technologies, and being a paid consultant and receiving research or institutional support as a principal investigator from Auxilium Pharmaceuticals. Dr. Stuchin has disclosed no relevant financial relationships.

American Academy of Orthopaedic Surgeons (AAOS) 2011 Annual Meeting: Abstract 568. Presented February 18, 2011.