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Purpose To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the same hand with Dupuytren fixed flexion contractures (FFCs). Methods Patients with 2 or more contractures in the same hand caused by palpable cords participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same hand (1 injection per affected joint) during the same visit. Finger extension was performed approximately 24, 48, or 72 or more hours later. Changes in FFC and range of motion, incidence of clinical success (FFC ≤ 5°), and adverse events (AEs) were summarized. Results The study enrolled 715 patients (725 treated joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98° to 27°. Mean total range of motion increased from 90° to 156°. The incidence of clinical success was 65% in metacarpophalangeal joints and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild to moderate, resolving without intervention; the most common were swelling of treated extremity, contusion, and pain in extremity. The incidence of skin lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of time to finger extension. Conclusions Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint, with the exception of skin laceration. The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint. Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints, and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment. Type of study/level of evidence Therapeutic III. © 2015 American Society for Surgery of the Hand. Source


Coleman S.,Brisbane Hand and Upper Limb Clinic | Gilpin D.,Brisbane Hand and Upper Limb Clinic | Tursi J.,Auxilium Pharmaceuticals | Kaufman G.,Auxilium Pharmaceuticals | And 2 more authors.
BMC Musculoskeletal Disorders | Year: 2012

Background: Dupuytren's contracture (DC) is a progressive fibroproliferative disorder characterized by development of nodules and collagen cords within the palmar fascia of the hand. Collagenase clostridium histolyticum (CCH) is currently approved in adults with DC for the nonsurgical treatment of a single palpable cord during a 30-day treatment cycle. This open-label pilot study was designed to examine the safety, efficacy, and multiple-dose pharmacokinetics of injecting two cords (affected joints) with multiple doses of CCH concurrently into the same hand in subjects with DC and multiple contractures. Methods: Twelve subjects with DC were enrolled, each with ≥3 contractures caused by palpable cords. Efficacy assessments were taken 30 days after treatment and adverse events (AEs) were recorded throughout. In the first treatment period, all subjects were injected with a single dose of CCH (0.58 mg) into a single cord. The same subjects entered a second treatment period 30 days later, where two different cords (affected joints) were injected concurrently on the same hand. A finger extension procedure was performed 24 hours after each administration of CCH to disrupt the enzymatically weakened cord. Results: For metacarpophalangeal (MP) joints, mean contracture reduction per joint treated was 29.0 ± 20.7 degrees following single injection vs 30.3 ± 10.9 degrees per treated joint following multiple injections. For proximal interphalangeal (PIP) joints, mean reduction in contracture was 30.7 ± 21.1 and 22.1 ± 4.9 degrees per treated joint, respectively, for the two periods. All patients (100%) were either "quite satisfied" or "very satisfied" following either treatment cycle. The most common treatment-related AEs were edema peripheral, contusion, and pain in the treated extremity; the differences in severity for local effects of the injections were minimal between treatment periods. No serious treatment-related AEs or systemic complications were reported. Conclusion: These results provide preliminary evidence that two cords (affected joints) can be treated concurrently with CCH with similar efficacy and safety as cords treated individually in a sequential fashion. Multiple concurrent injections would eliminate the 30-day wait between single treatments and allow for rapid and effective treatment of patients with multiple affected joints, a significant advantage for both patient and physician. Trial registration: Australian New Zealand Clinical Trials Registry #ACTRN12610001045000. Source


Gilpin D.,Brisbane Hand and Upper Limb Clinic | Gilpin D.,Emeritus Research | Gilpin D.,Caboolture Clinical Research Center | Gilpin D.,Peninsula Clinical Research Center | And 26 more authors.
Journal of Hand Surgery | Year: 2010

Purpose The Collagenase Option for the Reduction of Dupuytren's (CORD) II study investigated the efficacy and safety of injectable Xiaflex (collagenase clostridium histolyticum), in patients with Dupuytren's contracture. Methods This was a prospective, randomized, placebo-controlled trial with 90-day double-blind and 9-month open-label phases. We randomized patients with contractures affecting metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joints 2 to 1 to collagenase (0.58 mg) or placebo. Cords received a maximum of 3 injections. Cord disruption was attempted the day after injection using a standardized finger extension procedure. Primary end point was reduction in contracture to 0° to 5° of normal 30 days after the last injection. Results We enrolled 66 patients; 45 cords (20 MCP to 25 PIP joints) received collagenase and 21 cords (11 MCP to 10 PIP joints) received placebo in the double-blind phase. Statistically significantly more cords injected with collagenase than placebo met the primary end point (44.4% vs 4.8%; p <. 001). The mean percentage decrease in degree of joint contracture from baseline to 30 days after last injection was 70.5% ± 29.2% in the collagenase group and 13.6% ± 26.1% in the placebo group (p < .001). The mean increase in range of motion was significantly greater in the collagenase (35.4° ± 17.8°) than in the placebo (7.6° ± 14.9°; p < .001) group. Efficacy after open-label treatment was similar to that after the double-blind phase: 50.7% of all joints achieved 0° to 5° of normal. More patients were satisfied with collagenase (p < .001). No joint had recurrence of contracture. One patient had a flexion pulley rupture and one patient underwent routine fasciectomy to address cord proliferation and sensory abnormality. No tendon ruptures or systemic allergic reactions were reported. Most adverse events were related to the injection or finger extension procedure. Conclusions Collagenase clostridium histolyticum is the first Food and Drug Administrationapproved, nonsurgical treatment option for adult Dupuytren's contracture patients with a palpable cord that is highly effective and well tolerated. Type of study/level of evidence Therapeutic I. © 2010 American Society for Surgery of the Hand. Source


Coleman S.,Brisbane Hand and Upper Limb Clinic | Coleman S.,Indiana Hand to Shoulder Center | Coleman S.,Caboolture Clinical Research Center | Coleman S.,Auxilium Pharmaceuticals | And 28 more authors.
Journal of Hand Surgery | Year: 2014

Purpose To assess the safety and efficacy of 2 concurrent injections of collagenase clostridium histolyticum (CCH) in the same hand to treat multiple Dupuytren flexion contractures. Methods In a multicenter, open-label phase IIIb study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2 joints in the same hand during 1 visit, followed by finger extension approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion contracture and active range of motion, patient satisfaction, physician-rated improvement, and rates of clinical success [flexion contracture 5 or less]) and adverse events were summarized. Results The concurrent injections were most commonly administered in cords affecting metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on different fingers of the same hand (37%). Mean total (sum of the 2 treated joints) flexion contracture decreased 76%, from 87 to 24 (MCP joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100 to 161. Clinical success was 76% for MCP joints and 33% for PIP joints. Most patients were very satisfied (60%) or quite satisfied (28%) with treatment. Most investigators rated treated joints as very much improved (55%) or much improved (37%). The most common treatment-related adverse events (> 75% of patients) were contusion, pain in extremity, and edema peripheral (local edema). Most adverse events were mild to moderate in severity. Serious complications included 1 pulley rupture related to study medication and 1 flexor tendon rupture (following conclusion of the study). There were no systemic complications. Conclusions Results suggest that 2 affected joints can be effectively and safely treated with concurrent CCH injections. There was an increased incidence of some adverse events with concurrent treatment (pruritus, lymphadenopathy, blood blister, and skin laceration) compared with treatment of a single joint. High degrees of patient satisfaction and physician-rated improvement were reported. © 2014 by the American Society for Surgery of the Hand. All rights reserved. Source

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