Background Dupuytren’s disease is a progressive, fibroproliferative disorder resulting in nodules and collagenous cords within the palmar fascia of the hand. Until recently, surgery was the only treatment option for patients with Dupuytren’s contracture (DC). Collagenase Clostridium histolyticum (CCH) is a minimally invasive treatment approved in the US and Europe for the treatment of a single, palpable cord during a 30-day treatment cycle in adults with DC.
Objectives This small, open-label pilot study evaluated the safety, efficacy, and multiple-dose pharmacokinetics (PK) of simultaneous CCH treatment of 2 cords on the same hand in patients with multiple contractures.
Methods The study enrolled 12 patients with DC, each with ≥3 palpable cords causing contractures. Treatment efficacy was evaluated 30 days after CCH injection and adverse events (AEs) were recorded throughout the study period. All patients received a single dose of CCH (0.58 mg) injected into a single cord for the first treatment cycle. After 30 days, the same patients entered a second treatment cycle and received 2 doses of CCH (0.58 mg) in the same hand on the same day, thereby treating 2 different affected joints concurrently. Twenty four hours after each CCH injection, a finger extension procedure was performed to disrupt the enzymatically weakened cord. A local anaesthetic could be used during the finger extension procedure only after the first treatment cycle.
Results 22 metacarpophalangeal (MP) joints and 14 proximal interphalangeal (PIP) joints were treated. At 30 days post-injection, the mean reduction in contracture per treated joint was 29.0° and 30.7° in MP and PIP joints, respectively, after a single CCH injection. After concurrent CCH injections in 2 affected joints, the mean reduction in contracture per treated joint was 30.3° for MP joints and 22.1° for PIP joints. The mean change in range of motion increased by 30.0° in MP joints and 17.1° in PIP joints after multiple injections. After each treatment cycle, 100% of patients indicated they were “quite satisfied” or “very satisfied” with treatment. The most commonly reported treatment-related AEs were edema peripheral, contusion, and pain in the treated extremity, consistent with other published studies. Although the severity of AEs after the second treatment cycle was slightly greater, the difference versus the first treatment cycle was minimal. Most AEs resolved within 30 days, and no treatment-related serious AEs or systemic complications were reported. Systemic PK samples were below levels of CCH quantification.
Conclusions The results of this pilot study show that concurrent CCH treatment of 2 DC cords results in similar efficacy and safety profiles versus a sequential treatment regimen. While CCH is approved for the treatment of a single, palpable cord every 30 days, multiple, simultaneous injections would eliminate the need for the 30-day wait between injections and would facilitate more rapid and effective treatment of multiple affected joints. This would provide a significant advantage for patients and physicians.
Disclosure of Interest D. Gilpin: None Declared, S. Coleman: None Declared, J. Tursi Employee of: Auxilium Pharmaceuticals, N. Jones Employee of: Auxilium Pharmaceuticals, P. Szczypa Employee of: Pfizer Ltd