Collagenase Clostridium Histolyticum for the Treatment of Dupuytren Disease: A Delphi-Based Consensus Study.

Purpose: The aim of this study was to establish the consensus recommendations among hand surgeons who were experts in the use of collagenase clostridium histolyticum (CCH) on the appropriate treatment of Dupuytren disease in well-defined patient populations with varying degrees of disease severity and functional impairment. Methods: A three-round, blinded, modified Delphi process examined panelists' approaches to CCH treatment of metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures involving one or two fingers with varying degrees of severity. Clinical scenarios related to poor-quality skin, postfasciectomy scarring, boutonnière deformity, closed capsulotomy, and blood thinner use were also presented for panelist consideration. Panelists provided responses to clinical scenarios using a 5-point Likert scale or a yes/no response. Consensus was defined as ≥66.7% panelist agreement or disagreement. Results: Twenty panelists completed round 1; 19 of the 20 panelists completed rounds 2 and 3. Panelists achieved a high level of consensus for using CCH for the treatment of patients with palpable cords and varying severity contractures representing one- or two-finger MP joint contractures, most one- or two-finger PIP joint contractures, and most combined MP and PIP joint contractures. Consensus for the treatment of PIP joint contractures was mostly achieved, but clinical scenarios related to recurrent PIP contracture with poor-quality skin and/or significant postfasciectomy scarring, boutonnière deformity, PIP contractures >70°, closed capsulotomy, and blood thinner use were modified, and then most (95.3%) statements reached consensus for agreement in round 2. In round 3, open-ended responses indicated that panelists considered CCH appropriate for most patients with Dupuytren disease. Conclusions: Consensus-based findings among expert hand surgeons with substantial CCH experience indicated that CCH has a wide-ranging application for the treatment of Dupuytren disease in patients with varying degrees of disease severity and functional impairment. Type of study/level of evidence: Therapeutic V.

Incidence of Tendon Rupture After Collagenase Clostridium Histolyticum Injection for Treatment of Dupuytren Contracture in Adults: A Postmarketing Safety Analysis.

Purpose: Based, in part, on the clinical study reports of tendon rupture events after collagenase clostridium histolyticum (CCH) (Xiaflex, Endo Pharmaceuticals Inc) treatment for Dupuytren contracture (DC), a Risk Evaluation and Mitigation Strategy program was instituted in 2010 by Auxilium Pharmaceuticals (now Endo Pharmaceuticals Inc) to ensure that the benefits of CCH injection outweighed the risks when treating DC. Using the postmarketing surveillance data collected in this program, a retrospective analysis was conducted to evaluate the incidence of flexor tendon rupture after CCH treatment for DC in the clinical practice setting. Methods: The Endo Pharmaceuticals Inc safety database was searched for cases of tendon rupture reported between February 2, 2010, and October 8, 2015. Total number of CCH treatments for DC and incidence of tendon rupture were estimated using CCH dosing derived from clinical trial experience (1.7 CCH vials/treatment) or clinical practice evidence (1.08 CCH vials/treatment). Results: Over the 5.8-year surveillance period, 97,609 vials of CCH were distributed for the treatment of DC, equivalent to an estimated total of 57,416 treatments (at 1.7 CCH vials/treatment) or 90,378 treatments (at 1.08 CCH vials/treatment). Although CCH distribution increased during the surveillance period, reports of tendon rupture were infrequent (approximately 13 cases/y; total cases: flexor tendon, n = 57; ligament/pulley, n = 2), corresponding to a 0.10% (1.7 CCH vials/treatment) or 0.06% (1.08 CCH vials/treatment) mean estimated incidence of tendon rupture in patients with DC after CCH treatment. Conclusions: This retrospective analysis showed that flexor tendon rupture occurred infrequently in patients with DC who were treated with CCH in real-world practice settings between 2010 and 2015. On the basis of these findings and other favorable safety evidence, the Risk Evaluation and Mitigation Strategy program requirement for CCH for the treatment of DC was ended by the US Food and Drug Administration in November 2016. Type of study/level of evidence: Therapeutic IV.

A post hoc analysis of Dupuytren contracture treated with collagenase Clostridium histolyticum across disease stages.

This post hoc analysis from a multicenter study (NCT01674634) was designed to evaluate the efficacy of collagenase Clostridium histolyticum (CCH) treatment in patients with different stages of Dupuytren contracture. Previously untreated patients who received two concurrent injections of CCH in two affected joints in the same finger were assessed by disease severity (Tubiana stage). The mean (SD) improvement in total fixed flexion contraction (FFC) 31 days post-CCH treatment in 181 patients was: 71.1 (36.5)% for Tubiana I, 77.0 (21.0)% for Tubiana II, 72.0 (20.4)% for Tubiana III and 66.4 (22.2)% for Tubiana IV. Treatment of metacarpophalangeal and proximal interphalangeal joints in the same finger resulted in a mean (SD) improvement of 82.5 (24.8)% and 66.4 (27.9)%, respectively. In conclusion, CCH is an effective treatment alternative for all stages of Dupuytren contracture and it provides a less invasive treatment alternative to surgery with similar short-term efficacy in patients with more severe disease.

The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study.

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.

Correction of contracture and recurrence rates of Dupuytren contracture following invasive treatment: the importance of clear definitions.

PURPOSE: To call attention to the wide variety of definitions for recurrence that have been employed in studies of different invasive procedures for the treatment of Dupuytren contracture and how this important limitation has contributed to the wide range of reported results. METHODS: This study reviewed definitions and rates of contracture correction and recurrence in patients undergoing invasive treatment of Dupuytren contracture. A literature search was carried out in January 2011 using the terms "Dupuytren" AND ("fasciectomy" OR "fasciotomy" OR "dermofasciectomy" OR "aponeurotomy" OR "aponeurectomy") and limited to studies in English. RESULTS: The search returned 218 studies, of which 21 had definitions, quantitative results for contracture correction and recurrence, and a sample size of at least 20 patients. Definitions for correction of contracture and recurrence varied greatly among articles and were almost always qualitative. Percentages of patients who achieved correction of contracture (ie, responder rate) when evaluated at various times after completion of surgery ranged from 15% to 96% for fasciectomy/aponeurectomy. Responder rates were not reported for fasciotomy/aponeurotomy. Recurrence rates ranged from 12% to 73% for patients treated with fasciectomy/aponeurectomy and from 33% to 100% for fasciotomy/aponeurotomy. Review of these reports underscored the difficulty involved in comparing correction of contracture and recurrence rates for different surgical interventions because of differences in definition and duration of follow-up. CONCLUSIONS: Clearly defined objective definitions for correction of contracture and for recurrence are needed for more meaningful comparisons of results achieved with different surgical interventions. CLINICAL RELEVANCE: Recurrence after surgical intervention for Dupuytren contracture is common. This study, which evaluated reported rates of recurrence following surgical treatment of Dupuytren contracture, provides clinicians with practical information regarding expected long-term outcomes of surgical treatment choices. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and decision analysis III.

Results of needle aponeurotomy for Dupuytren contracture in over 1,000 fingers.

PURPOSE: To critically review the efficacy, recurrence rate, and complications of needle aponeurotomy (NA) for the treatment of Dupuytren contracture. METHODS: This was a retrospective study of the results of NA for the treatment of Dupuytren contracture. We included in the study all patients who had NA performed for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contracture of 20° or greater between March 2005 and May 2008. There were 474 patients with 1,013 fingers treated. The average age was 62 years (range, 33-92 y). Pre-procedure MP joint contracture averaged 35° (range, 15° to 95°), and PIP joint 50° (range, 15° to 110°). Immediately postprocedure and at least 3 years after treatment (range, 3.0-6.2 y), we measured MP and PIP joint contractures and reviewed records for complications. RESULTS: MP joint contractures were corrected an average of 99% and PIP contractures an average of 89% immediately postprocedure. At final follow-up, 72% of the correction was maintained for MP joints and 31% for PIP joints. The difference between the final corrections for MP versus PIP joints was statistically significant. When we compared the final results of patients age 55 years and older versus under 55 years, we found a statistically significant difference at both MP and PIP joints, with greater correction maintained in the older group. Gender differences were not statistically significant. Needle aponeurotomy provided successful correction to 5° or less contracture immediately postprocedure in 98% (791) of MP joints and 67% (350) of PIP joints. There was recurrence of 20° or less over the original postprocedure corrected level in 80% (646) of MP joints and 35% (183) of PIP joints. Complications were rare except for skin tears, which occurred in 3.4% (34) of digits. CONCLUSIONS: This study shows that NA is a safe procedure that can be performed in an outpatient setting. The complication rate was low, but recurrences were frequent in younger patients and for PIP contractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.