title: Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in dupuytren contracture: combined analysis of 4 phase 3 clinical trials.
abstract: OBJECTIVE
  To examine the results of proximal interphalangeal (PIP) joint contractures from 4 phase 3 clinical trials of collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture.
  
  
  METHODS
  Patients enrolled in Collagenase Option for Reduction of Dupuytren I/II and JOINT I/II with one or more PIP joint contractures (20° to 80°) received CCH 0.58 mg/0.20 mL or placebo (Collagenase Option for Reduction of Dupuytren I/II only) injected directly into a palpable cord. The percentage of PIP joints achieving clinical success (0° to 5° of full extension), clinical improvement (50% or more reduction in baseline contracture), and range of motion improvement at 30 days after the first and last CCH injections was assessed. The PIP joint contractures were classified into low (40° or less) and high (more than 40°) baseline severity. Adverse events were recorded.
  
  
  RESULTS
  A total of 506 adults (mean age, 63 ± 10 y; 80% male) received 1,165 CCH injections in 644 PIP joint cords (mean, 1.6 injections/cord). Most patients (60%) received 1 injection, with 24%, 16%, and 1% receiving 2, 3, and 4 injections, respectively. Clinical success and clinical improvement occurred in 27% and 49% of PIP joints after one injection and in 34% and 58% after the last injection. Patients with lower baseline severity showed greater improvement and response was comparable between fingers, as were improvements in range of motion. Adverse events occurring in more than 10% of patients were peripheral edema (58%), contusion (38%), injection site hemorrhage (23%), injection site pain (21%), injection site swelling (16%), and tenderness (13%). This incidence was consistent with data reported in phase 3 trials. Two tendon ruptures occurred. No further ruptures occurred after a modified injection technique was adopted.
  
  
  CONCLUSIONS
  Collagenase clostridium histolyticum was effective and well tolerated in the short term in patients with Dupuytren PIP joint contractures.
  
  
  METHODS
  Therapeutic II.
authors.affiliation: Department of Orthopaedics, State University of New York (SUNY) at Stony Brook Health Sciences Center, Stony Brook, NY; Department of Orthopaedic Surgery, Ronald Reagan UCLA Medical Center, Los Angeles, CA; Department of Biometrics, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA. Electronic address: marie.badalamente@stonybrookmedicine.edu.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Badalamente
authors.affiliation: Department of Orthopaedics, State University of New York (SUNY) at Stony Brook Health Sciences Center, Stony Brook, NY; Department of Orthopaedic Surgery, Ronald Reagan UCLA Medical Center, Los Angeles, CA; Department of Biometrics, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Hurst
authors.affiliation: Department of Orthopaedics, State University of New York (SUNY) at Stony Brook Health Sciences Center, Stony Brook, NY; Department of Orthopaedic Surgery, Ronald Reagan UCLA Medical Center, Los Angeles, CA; Department of Biometrics, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA.
authors.forename: Prosper
authors.initials: P
authors.lastname: Benhaim
authors.affiliation: Department of Orthopaedics, State University of New York (SUNY) at Stony Brook Health Sciences Center, Stony Brook, NY; Department of Orthopaedic Surgery, Ronald Reagan UCLA Medical Center, Los Angeles, CA; Department of Biometrics, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D047009:Hathewaya histolytica / Q000201:enzymology*; D004387:Dupuytren Contracture / Q000188:drug therapy*; D005260:Female; D050278:Finger Phalanges; D006801:Humans; D007267:Injections; D008297:Male; D003012:Microbial Collagenase / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D003012:Microbial Collagenase
keywords: Collagenase clostridium histolyticum; Dupuytren contracture; nonsurgical treatment; proximal interphalangeal joint