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Injectable Collagenase Clostridium Histolyticum: A New Nonsurgical Treatment for Dupuytren's Disease

  • David Gilpin
    Correspondence
    Corresponding author: David Gilpin, MBBS, Brisbane Hand and Upper Limb Clinic, Level 9, 259 Wickham Terrace, Brisbane, Queensland, Australia 4001
    Affiliations
    Brisbane Hand and Upper Limb Clinic, Brisbane, Queensland; Rivercity Private Hospital, Auchenflower, Queensland; Emeritus Research, Malvern, Victoria; Caboolture Clinical Research Centre, Caboolture, Queensland; Peninsula Clinical Research Centre, Kippa Ring, Queensland, Australia; and Auxilium Pharmaceuticals, Malvern, PA
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  • Stephen Coleman
    Affiliations
    Brisbane Hand and Upper Limb Clinic, Brisbane, Queensland; Rivercity Private Hospital, Auchenflower, Queensland; Emeritus Research, Malvern, Victoria; Caboolture Clinical Research Centre, Caboolture, Queensland; Peninsula Clinical Research Centre, Kippa Ring, Queensland, Australia; and Auxilium Pharmaceuticals, Malvern, PA
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  • Stephen Hall
    Affiliations
    Brisbane Hand and Upper Limb Clinic, Brisbane, Queensland; Rivercity Private Hospital, Auchenflower, Queensland; Emeritus Research, Malvern, Victoria; Caboolture Clinical Research Centre, Caboolture, Queensland; Peninsula Clinical Research Centre, Kippa Ring, Queensland, Australia; and Auxilium Pharmaceuticals, Malvern, PA
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  • Anthony Houston
    Affiliations
    Brisbane Hand and Upper Limb Clinic, Brisbane, Queensland; Rivercity Private Hospital, Auchenflower, Queensland; Emeritus Research, Malvern, Victoria; Caboolture Clinical Research Centre, Caboolture, Queensland; Peninsula Clinical Research Centre, Kippa Ring, Queensland, Australia; and Auxilium Pharmaceuticals, Malvern, PA
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  • Jeff Karrasch
    Affiliations
    Brisbane Hand and Upper Limb Clinic, Brisbane, Queensland; Rivercity Private Hospital, Auchenflower, Queensland; Emeritus Research, Malvern, Victoria; Caboolture Clinical Research Centre, Caboolture, Queensland; Peninsula Clinical Research Centre, Kippa Ring, Queensland, Australia; and Auxilium Pharmaceuticals, Malvern, PA
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  • Nigel Jones
    Affiliations
    Brisbane Hand and Upper Limb Clinic, Brisbane, Queensland; Rivercity Private Hospital, Auchenflower, Queensland; Emeritus Research, Malvern, Victoria; Caboolture Clinical Research Centre, Caboolture, Queensland; Peninsula Clinical Research Centre, Kippa Ring, Queensland, Australia; and Auxilium Pharmaceuticals, Malvern, PA
    Search for articles by this author

      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 Administration–approved, 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.

      Key words

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