Collagenase Clostridium histolyticum: emerging practice patterns and treatment advances.

OBJECTIVE: This study aims to provide a comprehensive review of the role of Collagenase Clostridium histolyticum (CCH). METHODS: This review is based on a literature review and practical experience. RESULTS: This review provides practical management strategies for using collagenase by sharing clinical experiences over the past few years; logistical aspects of in-clinic treatment, lessons learned, and novel approaches to correct traditionally hard-to-treat contractures are discussed. In addition a brief, yet comprehensive overview is provided on the pathophysiology of the disease, the mechanism of collagenase action and results of clinical studies. CONCLUSION: CCH has an evolving role as one of the tools available for treating Dupuytren's disease.

Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: short-term results from 2 open-label studies.

PURPOSE: The JOINT I (United States) and JOINT II (Australia and Europe) studies evaluated the efficacy and safety of collagenase clostridium histolyticum (CCH) injection for the treatment of Dupuytren contracture. METHODS: Both studies used identical open-label protocols. Patients with fixed-flexion contractures of metacarpophalangeal (MCP) (20° to 100°) or proximal interphalangeal (PIP) joints (20° to 80°) could receive up to three 0.58-mg CCH injections per cord (up to 5 total injections per patient). We performed standardized finger extension procedures to disrupt injected cords the next day, with follow-up 1, 2, 6, and 9 months thereafter. The primary end point (clinical success) was reduction in contracture to within 0° to 5° of full extension 30 days after the last injection. Clinical improvement was defined as 50% or more reduction from baseline contracture. RESULTS: Dupuytren cords affecting 879 joints (531 MCP and 348 PIP) in 587 patients were administered CCH injections at 14 U.S. and 20 Australian/European sites, with similar outcomes in both studies. Clinical success was achieved in 497 (57%) of treated joints using 1.2 ± 0.5 (mean ± SD) CCH injections per cord. More MCP than PIP joints achieved clinical success (70% and 37%, respectively) or clinical improvement (89% and 58%, respectively). Less severely contracted joints responded better than those more severely contracted. Mean change in contracture was 55° for MCP joints and 25° for PIP joints. With average contracture reductions of 73% and improvements in range of motion by 30°, most patients (92%) were "very satisfied" (71%) or "quite satisfied" (21%) with treatment. Physicians rated change from baseline as "very much improved" (47%) or "much improved" (35%). The CCH injections were well tolerated, causing no tendon ruptures or systemic reactions. CONCLUSIONS: Collagenase clostridium histolyticum was an effective, minimally invasive option for the treatment of Dupuytren contracture of a broad range of severities. Most treated joints (625 of 879) required a single injection. Treatment earlier in the course of disease provided improved outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Determining clinically important changes in range of motion in patients with Dupuytren's Contracture: secondary analysis of the randomized, double-blind, placebo-controlled CORD I study.

BACKGROUND AND OBJECTIVE: Injectable collagenase Clostridium histolyticum is efficacious in correcting Dupuytren's contracture as assessed by changes in the angle of contracture and range of motion (ROM). However, clinically important changes in ROM have not been evaluated in depth. The objective of this secondary analysis of the CORD I trial was to identify severity levels using baseline ROM, estimate a clinically important difference (CID) for ROM, and link the results to collagenase treatment and patient satisfaction. METHODS: In the CORD I trial, patients with Dupuytren's disease and joint contractures ≥20° were randomized to receive a maximum of three collagenase 0.58 mg or placebo injections into the cord of the affected hand at 30-day intervals. The primary endpoint was reduction in contracture to ≤5° 30 days after the last injection (day 30). The secondary endpoints, which are reported in this analysis, were ROM, physician- and patient-rated severity ('normal', 'mild', 'moderate', 'severe') and improvement, and treatment satisfaction. Linear regression was used to model data for severity classification and CID estimation for ROM based on physician and patient ratings. RESULTS: At baseline, mean ROM was 43.9° in the collagenase-treated joints (n = 197) and 45.3° in the placebo-treated joints (n = 102). On day 30, mean ROM was 80.7° in the collagenase-treated joints and 49.5° in the placebo-treated joints. The mean increase in ROM was 36.7° in the collagenase-treated joints (p < 0.001) and 4.0° in the placebo-treated joints (not significant). The estimated CID for ROM was 13.5° (95% CI 11.9, 15.1), reflecting a one-category change in severity. The mean increase in ROM exceeded the CID in the collagenase-treated joints but not in the placebo-treated joints; the difference between collagenase treatment and placebo in the mean increase in ROM also exceeded the CID, implying that the improvement with collagenase was clinically relevant. The severity classification for ROM was: ≥67.0° ('normal'), ≥54.3 and <67.0° ('mild'), ≥41.6 and <54.3° ('moderate'), and <41.6° ('severe'). More collagenase- than placebo-treated patients achieved 'normal' (81% vs 25%; p < 0.0001) status, and more collagenase- than placebo-treated patients reported being 'very/quite satisfied' (87% vs 32%; p < 0.001). CONCLUSION: Injectable collagenase significantly improves ROM and treatment satisfaction versus placebo. ROM improvements are clinically relevant as well as statistically significant. These data support the potential need to include ROM and physician- and patient-rated severity and satisfaction as standard assessments for Dupuytren's contracture treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00528606; other study identification number: AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).