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Introduction: Collagenase clostridium histolyticum (CCH) is FDA-approved (Feb 2010) for treatment of adults with Dupuytren’s contracture with palpable cord. CCH is injected directly into the cord, followed (~24 hours later) by a passive finger extension procedure that facilitates cord disruption and joint extension. In clinical trials (1082 patients; 2630 injections), 97.1% of patients receiving CCH experienced an adverse drug reaction (ADR). Most were localized to the injected extremity as follows: peripheral edema (77.4%), injection site swelling (24.1%); injection site pain (40.6%), extremity pain (36.2%); contusion (54.4%), ecchymosis (17.9%); hemorrhage (34.1%), laceration (11.1%); injection site pruritus (5.2%); pruritus (12.6%), lymphadenopathy (11.1%), axillary pain (6.7%). The majority of ADRs were mild to moderately severe and resolved spontaneously. Other ADRs included 3 flexor tendon ruptures, 1 pulley injury, and 3 cases of hypersensitivity reaction.

Objective: To summarize CCH adverse events received by the manufacturer in the first 12 months post-approval (~5400 doses).

Methods: A search of global safety data for CCH adverse events (AE) received during the first 12 months after U.S. approval identified 270 adverse events in 115 patients (reporting rate ~50 AE/1000 doses).  Reporting rates were used because incidence rates cannot be determined from voluntary postmarketing data.

Results: The AEs reported during the first postmarketing year were similar in type and severity to those reported in clinical trials and no safety-related label changes were made. Skin laceration was the most commonly reported AE at 6.5/1000 doses, local edema at 5.6/1000 and contusion at 4.8/1000. Skin lacerations occurred during the finger extension procedure and typically healed without intervention; however, there were two reports that described skin grafting. Three of the most important and likely treatment-related events were local hypersensitivity reaction (4 reports), flexor tendon rupture (2 reports), and pulley injury (1 report).  There were no reports of nerve injury thought to be related to CCH.

Conclusion: The postmarketing safety data received in the first year following product approval in U.S. suggest a similar safety profile compared with the profile established in the clinical trials. Local, nonserious reactions to treatment were the most frequent reports received.  More serious but rare AEs, such as skin tears that require grafting and flexor tendon ruptures, are important to note and to understand as both unlikely but serious concerns.