Badalamente Marie A, Hurst Lawrence C, Benhaim Prosper, Cohen Brian M
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.
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.
J Hand Surg Am. 2015 May;40(5):975-83. doi: 10.1016/j.jhsa.2015.02.018. Epub 2015 Apr 2.
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.
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.
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.
Collagenase clostridium histolyticum was effective and well tolerated in the short term in patients with Dupuytren PIP joint contractures.
TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.
研究溶组织梭菌胶原酶（CCH）注射治疗掌腱膜挛缩症的4项3期临床试验中近端指间关节（PIP）挛缩的结果。
入选Dupuytren挛缩症减少胶原酶方案I/II和关节I/II且有一个或多个PIP关节挛缩（20°至80°）的患者，将0.58 mg/0.20 mL的CCH或安慰剂（仅Dupuytren挛缩症减少胶原酶方案I/II）直接注射到可触及的条索中。评估首次和末次CCH注射后30天时达到临床成功（完全伸直0°至5°）、临床改善（基线挛缩减少50%或更多）以及活动范围改善的PIP关节百分比。PIP关节挛缩分为低基线严重程度（40°或以下）和高基线严重程度（超过40°）。记录不良事件。
共有506名成年人（平均年龄63±10岁；80%为男性）在644条PIP关节条索中接受了1165次CCH注射（平均每条条索1.6次注射）。大多数患者（60%）接受1次注射，分别有24%、16%和1%的患者接受2次、3次和4次注射。一次注射后，27%的PIP关节实现临床成功，49%实现临床改善；末次注射后，这两个比例分别为34%和58%。基线严重程度较低的患者改善更大，各手指间的反应相当，活动范围的改善情况也相当。超过10%的患者发生的不良事件有外周水肿（58%）、挫伤（38%）、注射部位出血（23%）、注射部位疼痛（21%）、注射部位肿胀（16%）和压痛（13%）。这一发生率与3期试验报告的数据一致。发生了2例肌腱断裂。采用改良注射技术后未再发生断裂。
溶组织梭菌胶原酶对掌腱膜PIP关节挛缩症患者在短期内有效且耐受性良好。
研究类型/证据水平：治疗性II级。
