Adjuvant Treatment with Celecoxib after Collagenase Injection for Dupuytren Contracture: A Double-Blind Randomised Controlled Trial.

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).

A 10-Year Review of Collagenase Versus Fasciectomy in the Treatment of Dupuytren Contracture.

BACKGROUND: Dupuytren disease (DD) is one of the most common disorders of the hand, affecting 5.7% to 11.7% of the global population. This study seeks to evaluate the 10-year efficacy of the 2 most prominent treatment modalities for DD in Veterans Affairs hospitals, injectable collagenase Clostridium histolyticum versus open fasciectomy. METHODS: A retrospective review was conducted of all electronic medical records of patients who underwent open fasciectomy or collagenase injection to treat their persistent Dupuytren contracture between April 2011 and April 2021. All procedures were performed by 1 of 5 senior surgeons at the same Veterans Affairs Hospital. RESULTS: A total of 232 patients were treated for DD, with 247 collagenase injections and 44 open fasciectomies performed in this sample. Collagenase patients were, on average, 6.51 years after intervention at the time of review. Open fasciectomy patients were, on average, 4.56 years after operation at the time of review. Collagenase decreased contractures, on average, by 29.40 degrees, whereas open fasciectomy decreased contractures, on average, by 38.59 degrees. Of the contractures that were initially classified as resolved, 50 of 155 (32.2%) treated with collagenase and 6 of 56 (10.7%) treated with open fasciectomy recurred. The use of open fasciectomy compared with collagenase injections to treat contracture was associated with a 74.2% decrease in the likelihood of recurrence. CONCLUSIONS: This study found that treatment of DD with collagenase injection is associated with a significantly lower degree of deformity correction, lower rate of resolution, and increased rate of recurrence when compared with open fasciectomy.

Conservative treatment of Peyronie's disease: a guide.

PURPOSE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. RESULTS: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

Long-term recurrence of Dupuytren's disease treated with clostridium histolitycum collagenase. Surgical treatment and anatomopathological study.

OBJECTIVE: To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren's disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase. MATERIALS AND METHODS: In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment. RESULTS: In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy. CONCLUSIONS: Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection. LEVEL OF EVIDENCE: III.

Efficacy of collagenase Clostridium histolyticum combination therapies for Peyronie's disease: a systematic review and meta-analysis.

INTRODUCTION: Peyronie's disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase Clostridium histolyticum (CCH) is an injectable drug that treats PD by enzymatically degrading plaque interstitial collagen. CCH has been used in patients with varying curvature, as well as in the acute and stable phases of the disease, through a variety of treatment regimens and combinations. We carried out a systematic review and meta-analysis to assess the efficacy of CCH combination therapies for PD. METHODS: We selected 4 observational comparative studies and 3 randomized controlled trials including 532 participants from the PubMed, Embase, and Cochrane databases (until December 2023) to evaluate the efficacy of CCH combination therapies for PD. The primary outcome was clinical efficacy as evaluated by improvement in penile curvature and penile length, as well as by scores on the Peyronie's Disease Questionnaire (PDQ) for symptom bother, penile pain, and psychological symptoms. Continuous data were represented by mean difference (MD) and 95% CI. All data were analyzed by Review Manager version 5.3. RESULTS: For penile length (MD, 0.81 cm; 95% CI, 0.17-1.45; P = .01), PDQ symptom bother (MD, -1.02; 95% CI, -1.83 to -0.21; P = .01), and PDQ penile pain (MD, -0.93; 95% CI, -1.50 to -0.36; P = .001), CCH combination therapy showed significantly greater improvements vs CCH monotherapy. However, in the other indicators, penile curvature and PDQ psychological symptoms, there was no significant difference between the therapies. CONCLUSION: This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent. However, CCH combination therapies still need to be evaluated through more high-quality research.

Collagenase Clostridium histolyticum for Peyronie's disease: a contemporary atlas of complications and their management.

INTRODUCTION: Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie's disease (PD). The initial IMPRESS I and II trials (Investigation for Maximal Peyronie's Reduction Efficacy and Safety), which led to Food and Drug Administration approval, revealed a rate of treatment-related adverse events as high as 84%. Studies fail to provide clear definitions of complications. OBJECTIVES: To review complications, provide a CCH complication atlas, and propose management strategies for commonly encountered complications. METHODS: We performed a literature review using PubMed. A photographic atlas was provided regarding complications in patients in a high-volume CCH center for PD. RESULTS: Complications were identified and classified by nature and severity. We followed a standardized previously published grading system for hematomas. Complications include bruising, swelling, hematoma formation, back pain, and, rarely, corporal rupture. Complications were discussed, and hematomas were graded by penile surface area. Complication photographs were graded and displayed. Treatment-related adverse effects do not affect overall results. CONCLUSION: Recognizing and grading complications associated with CCH therapy for PD is crucial for effective patient management and informed decision making. A standardized grading system allows for consistency in reporting and comparing hematoma complication rates across studies and patient populations. Herein we provide images that will help clinicians identify and confidently manage common complications that may occur in any CCH program.

Industry Sponsorship Bias in Collagenase Clinical Trials for Dupuytren Disease: A Meta-analysis.

BACKGROUND: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias. METHODS: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies. RESULTS: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection. CONCLUSIONS: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application.

A contemporary assessment of the evaluation and management of patients presenting to a tertiary medical center with Peyronie's disease.

Peyronie's disease continues to be poorly understood. We characterize the presenting features of Peyronie's disease within a large cohort and elucidate the factors that correlate with surgical intervention. Univariate and multivariate analyses were performed on 1483 consecutive patients to assess pre-operative predictors of surgical intervention for Peyronie's disease. Overall, 1263 patients met inclusion criteria. Mean age was 55.4 ± 11.1 years with a mean duration of disease at presentation of 33.2 ± 42.5 months. Mean primary curvature was 49.8 ± 20.8°. Primary ventral curvature was present in 11.4% and 36.5% of patient had a multiplanar curvature. During penile duplex ultrasound evaluation indentation/narrowing deformities were appreciated in 76.0%, hourglass deformity in 10.1%, and hinge effect in 33.0% of patients. Calcification was seen in 30.1% of patients. Operative intervention occurred in 35.3% of patients. Degree of primary curvature (1.03 OR, p < 0.001), hourglass deformity (1.82 OR, p = 0.01), decreased tunical elasticity (1.20 OR, p = 0.03), and prior intralesional collagenase clostridium histolyticum injections (2.94 OR, p < 0.001) predicted surgical correction on multivariate analysis. Compared to historical studies, we found a higher incidence of severe degree of curvature (27.5% >60°), indentation deformities, hinge-effect, multiplanar curvature and penile calcifications. Ultimately, predictors of surgical intervention included those with worse erectile function and more severe characteristics.

Collagenase clostridium histolyticum injection versus limited fasciectomy for the treatment of Dupuytren's disease: a systematic review and meta-analysis of comparative studies.

INTRODUCTION: The aim of the present study is to systematically review the literature on well-selected comparative studies for meta-analysis on outcome differences between collagenase clostridium histolyticum (CCH) injection and limited fasciectomy (LF) for Dupuytren's disease. MATERIALS AND METHODS: PubMed/Medline, Embase, and the Cochrane Library were searched for comparative studies assessing differences in outcomes of CCH and LF. Effect estimates were pooled across studies using random effects models and presented as weighted mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: A total of 11 studies encompassing 1'051 patients was included (619 patients in the CCH and 432 in the LF group). The residual contracture at a minimal average follow-up of three months was higher in the CCH group than in the LF group (27.8 vs. 16.2°, MD 11.6°, 95% CI [8.7, 14.5°], p < 0.001). The recurrence rate was significantly higher in the CCH group (25.8 vs. 9.3%, OR 5.2, 95% CI [1.5, 18.8], p = 0.01) while the rate of severe complications was significantly higher in the LF group (0.3 vs. 7.3%, OR 0.12, 95% CI [0.03, 0.42], p = 0.001). CONCLUSIONS: Evidence of the present study confirms that CCH injection has a higher rate of disease recurrence whereas LF carries a higher risk for severe complications. It's imperative that the trade-off between these aspects is considered, keeping in mind that CCH injections may be repeated in case of disease recurrence without increasing procedure related risks, especially in complex cases.

Peyronie's disease response to intralesional collagenase clostridium histolyticum therapy is independent of baseline testosterone.

BACKGROUND: Testosterone plays an important role in collagen metabolism, transforming growth factor-ß1 expression, and wound healing, which are all critical factors in pathogenesis of Peyronie's disease. Some clinical studies have suggested an association between Peyronie's disease and hypogonadism. OBJECTIVE: We sought to investigate whether baseline total testosterone levels influence response to intralesional collagenase clostridium histolyticum in Peyronie's disease. METHODS: A retrospective review of patients receiving collagenase clostridium histolyticum injections with available total testosterone levels within 1 year of initial injection was conducted at a single institution. Baseline demographics, hypogonadal status, total testosterone, number of collagenase clostridium histolyticum cycles, and pre- and post-treatment degrees of curvature were collected. Hypogonadism was defined as total testosterone <300 ng/dL. RESULTS AND DISCUSSION: Thirty-six men were included with mean age of 58.2 years (SD 10.4) and mean body mass index 26.8 (SD 3.2). The mean total testosterone was 459.2 ng/dL (SD 144.0), and four (11.1%) were hypogonadal. Mean pre-treatment curvature was 47.6°, and mean post-treatment curvature was 27.8°, with mean improvement of 19.9° (40.1%). Hypogonadal status was not significantly associated with more severe curvature, 46.4° among hypogonadal men as to 57.5° among eugonadal men (p = 0.32). On linear regression analysis, total testosterone did not significantly predict improvement in degrees (ß = -0.02; R2 = 0.06; p = 0.14) or percent (ß = 0.0; R2 = 0.05; p = 0.18). Improvement in neither degrees nor percent differed significantly by hypogonadal status (p = 0.41 and 0.82, respectively). The cycle number did significantly predict greater improvement in curvature on both univariate and multivariate analyses (ß = 5.7; R2 = 0.34; p < 0.01). CONCLUSION: Neither total testosterone nor hypogonadism is associated with a degree of improvement after collagenase clostridium histolyticum treatment.

A survey of exposure to the use of Xiaflex for the treatment of Peyronie's disease among United States urology residency programs.

Xiaflex® (collagenase clostridium histolyticum) is a Food and Drug Administration-approved treatment for patients with Peyronie's disease. Despite its approval and implementation, there is concern that urologists in training are offered minimal exposure to its use. Thus, the purpose of this study was to evaluate the exposure of urology residents to Peyronie's disease and its management, particularly Xiaflex®. A Google Forms survey regarding the exposure of residents to Peyronie's disease and use of Xiaflex® was created and disseminated through email to urology programs. Overall, 47 institutional responses were received. At 45 institutions (95.7%), residents receive training in directly evaluating and caring for patients with Peyronie's disease. At 46 institutions (97.9%), residents receive training in observing and/or performing surgical procedures for Peyronie's disease. Residents at 31 institutions (66.0%) receive observational or procedural training for non-surgical management of Peyronie's disease, specifically Xiaflex®. Residents receive non-surgical training from an academic faculty who is fellowship trained in sexual medicine at 25 institutions and an academic faculty not trained in sexual medicine at six institutions. There exists a glaring disparity in residency exposure to Xiaflex®. Further research is warranted to elucidate how programs can provide residents with further exposure to the use of Xiaflex® in patients with Peyronie's disease.

Long-term clinical outcome of collagenase clostridium histolyticum treatment is independent of Dupuytren Diathesis Score.

Collagenase clostridium histolyticum (CCH) is a pharmaceutical, non-surgical treatment option for Dupuytren Disease. However, recurrence is common, and predictors of treatment outcome of CCH treatment are largely unknown. In this retrospective study, we analysed the possible correlation between Abe's Dupuytren Diathesis Score (DDS) and recurrence after treatment with CCH. In a total of 74 patients, with an average follow-up of 5 years, we found an overall recurrence rate of 67% after 5y but no correlation with DDS. Sub-scale analysis indicated that the presence of knuckle pads was associated with a reduced recurrence risk. Patient satisfaction after CCH was high. Deriving from our data, there is no correlation between DDS and recurrence following CCH treatment. Therefore, at this moment, we do not advocate the use of the DDS when informing patients about recurrence rates after CCH treatment. Level of evidence: IV: therapeutic cohort study.

Significant Geographic Variation in Access to Certified Collagenase Clostridium histolyticum Injectors for Peyronie's Disease Throughout the United States.

INTRODUCTION: We characterize the geographic distribution of providers trained to inject Clostridium histolyticum and identify areas with low provider availability. METHODS: We utilized a publicly available search tool to identify clinical sites offering Clostridium histolyticum in the US The data gathered included the provider's name, specialty, address, and whether the site was considered high-volume (ie, administer ≥20 Clostridium histolyticum injections per year). Data were compared to the AUA Census. RESULTS: In total, 2,388 clinical sites offering Clostridium histolyticum were identified. A total of 894 sites (37%) were high-volume sites. The mean number of locations offering Clostridium histolyticum per 100,000 state residents was 0.69 (SD 0.27). Georgia (1.28), Rhode Island (1.13), and Alaska (1.10) had the highest number, whereas New Mexico (0.10), Maine (0.22), and Delaware (0.30) had the lowest. The mean proportion of urologists providing Clostridium histolyticum to total urologists was 0.17 (SD 0.07). The 3 states with the highest proportion were Georgia (0.37), Alaska (0.31), and Utah (0.30), whereas New Mexico (0.03), Maine (0.05), and Vermont (0.06) had the lowest. CONCLUSIONS: States with low numbers of clinical sites offering Clostridium histolyticum per 100,000 residents relative to other states also had a low total ratio of urologists offering Clostridium histolyticum as a treatment. There is room for urologists in these states and others to expand their practice to offer Clostridium histolyticum and improve patient access to this important nonsurgical treatment option.

Comparison of Collagenase Clostridium histolyticum to Surgery for the Management of Peyronie's Disease: A Randomized Trial.

PURPOSE: Since Food and Drug Administration approval of collagenase Clostridium histolyticum for Peyronie's disease, there has been significant debate regarding its role and comparable efficacy to surgery. MATERIALS AND METHODS: A randomized, controlled trial was performed of Peyronie's disease men treated with either collagenase C histolyticum + RestoreX penile traction therapy + sildenafil or penile surgery + RestoreX penile traction therapy + sildenafil, with 3-month data presented. Primary objectives were overall satisfaction, subjective changes in erectile function, penile sensation, penile length, and changes in the International Index of Erectile Function-Erectile Function Domain score. Secondary outcomes included objective changes in length, curve, adverse events, and other standardized and nonstandardized questionnaires. RESULTS: A total of 40 men were enrolled, with 38 (collagenase C histolyticum group = 19, surgery group = 19) completing treatment and having 3-month data available. All demographic and clinicopathological variables were similar between groups. Following treatment, 50% of men in the collagenase C histolyticum group reported being very satisfied (vs 21% in the surgery group, P = .08) and noted better subjective erectile function (100% vs 68%, P = .03) and penile length (88% vs 16%, P < .0001), lesser impacts on penile sensation (75% vs 11% no change, P < .001), and similar International Index of Erectile Function-Erectile Function Domain changes (+1.5 vs +2.5, P = .91). Objectively, men in the surgery group had greater curve improvements (84% vs 54%, P < .01) and higher rates of adverse events (50 vs 13 events, P < .001) but decreased penile length (-0.5 cm vs +1.0 cm, P < .01). CONCLUSIONS: At 3 months posttreatment, collagenase C histolyticum + RestoreX penile traction therapy + sildenafil results in lesser curve improvements but greater penile length and fewer adverse events, including impacts on subjective erectile function and sensation, than men treated with surgery.

Collagenase Treatment Versus Needle Fasciotomy for Single-Digit Dupuytren Contractures: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to synthesize the available randomized controlled trial data comparing needle fasciotomy and collagenase treatment for single-digit Dupuytren contractures with a minimum of 3-year follow-up and determine whether one treatment is superior regarding contracture correction and functional outcomes. METHODS: A systematic review and meta-analysis was conducted by searching four databases for randomized controlled trials investigating the single-digit treatment outcomes for Dupuytren contracture comparing collagenase treatment and needle fasciotomy with a minimum of 3-year follow-up. The risk of bias of included studies was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed using a random effects model in anticipation of unobserved heterogeneity. The primary outcome measure was contracture recurrence. Secondary outcome measures included final fixed flexion contracture (FFC), Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores, and Unité Rhumatologique des Affections de la Main (URAM) scores. RESULTS: After screening 264 articles, 4 randomized clinical trials were eligible for final inclusion. One trial had a high risk of bias, and two trials had some concern for bias. The final meta-analysis included 347 patients, 169 who underwent collagenase treatment and 178 who underwent needle fasciotomy. No significant differences were noted between the groups in contracture recurrence, FFC, and URAM scores. The pooled data showed a higher QuickDASH score in the collagenase treatment group compared with the needle fasciotomy group, but the observed difference was less than what would be expected to be clinically relevant. CONCLUSIONS: Needle fasciotomy and collagenase treatment have similar outcomes with regards to contracture recurrence, final FFC, QuickDASH scores, and URAM scores for the single-digit treatment for Dupuytren contracture at a minimum of 3-year follow-up. Relevant factors that may be considered during the shared decision-making process for treatment selection include surgeon and patient preferences, costs of treatment, and the disparate complication profiles of these two treatments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Collagenase treatment decreases muscle stiffness in cerebral palsy: A preclinical ex vivo biomechanical analysis of hip adductor muscle fiber bundles.

AIM: To determine the dose-response relationship of collagenase Clostridium histolyticum (CCH) on collagen content and the change in muscle fiber bundle stiffness after ex vivo treatment of adductor longus biopsies with CCH in children with cerebral palsy (CP). METHOD: Biopsy samples of adductor longus from children with CP (classified in Gross Motor Function Classification System levels IV and V) were treated with 0 U/mL, 200 U/mL, 350 U/mL, or 500 U/mL CCH; percentage collagen reduction was measured to determine the dose-response. Peak and steady-state stresses were determined at 1%, 2.5%, 5%, and 7.5% strain increments; Young's modulus was calculated. RESULTS: Eleven patients were enrolled (nine males, two females, mean age at surgery 6 years 5 months; range: 2-16 years). A linear CCH dose-response relationship was determined. Peak and steady-state stress generation increased linearly at 5.9/2.3mN/mm2 , 12.4/5.3mN/mm2 , 22.2/9.7mN/mm2 , and 33.3/15.5mN/mm2 at each percentage strain increment respectively. After CCH treatment, peak and steady-state stress generation decreased to 3.2/1.2mN/mm2 , 6.5/2.9mN/mm2 , 12.2/5.7mN/mm2 , and 15.4/7.7mN/mm2 respectively (p < 0.004). Young's modulus decreased from 205 kPa to 100 kPa after CCH (p = 0.003). INTERPRETATION: This preclinical ex vivo study provides proof of concept for the use of collagenase to decrease muscle stiffness in individuals with CP.

Pharmacotherapies in Dupuytren Disease: Current and Novel Strategies.

Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for use in Dupuytren disease. There is a great need for additional nonsurgical methods that can be used to either avoid the risks of invasive treatments or help minimize recurrence rates following treatment. A number of nonsurgical modalities have been discussed in the past and continue to appear in discussions among hand surgeons, despite highly variable and often poor or no long-term clinical data. This article reviews many of the pharmacotherapies discussed in the treatment of Dupuytren disease and novel therapies used in inflammation and fibrosis that offer potential treatment options.

Dupuytren's Contracture Recurrence and Treatment Following Collagenase Clostridium Histolyticum Injection: A Longitudinal Assessment in a Veteran Population.

INTRODUCTION: Dupuytren's contracture is a connective tissue disease characterized by an abnormal proliferation of collagen in the palm and fingers, which leads to a decline in hand function because of progressive joint flexion. In addition to surgical and percutaneous interventions, collagenase clostridium histolyticum (CCH, trade name Xiaflex) is an intralesional enzymatic treatment for adults with palpable cords. The objectives of this study are to evaluate factors predictive of recurrence following treatment with CCH and to review the outcomes of repeat treatments with CCH for recurrent contracture. MATERIALS AND METHODS: An institutional review board-approved retrospective chart review was conducted for patients between 2010 and 2017 who received CCH injections for Dupuytren's contracture at a Veterans Affairs hospital. Demographics, comorbidities, affected finger and joint, pre/posttreatment contracture, time to recurrence, and treatment of recurrence were recorded. Successful treatment was defined as contracture ≤5° following CCH, and improvement was defined as ≥20° reduction from baseline contracture. Study cohorts were followed after their secondary treatment, and time to recurrence was recorded and plotted using a Kaplan-Meier curve. A Cox proportional hazards model was used to compare treatment group risk factors for recurrence with a P-value less than .05 defined as statistical significance. RESULTS: Of 174 injections performed for the correction of flexion deformities in 109 patients, 70% (121) were successfully treated with CCH, and an additional 20% (35) had improvement. There was a recurrence of contractures in 43 joints (25%). Of these, 16 contractures were treated with repeat CCH, whereas another 16 underwent limited fasciectomy. In total, 75% (12 of 16) of the repeat CCH group and 75% of the fasciectomy group were successfully treated. Pre-injection contracture of ≥25° was found to be predictive of recurrence (P < .05). CONCLUSIONS: Initial treatment of contracture with CCH had a 70% success rate with 25% recurrence during the study period. Compared with limited fasciectomy, CCH had decreased efficacy. Based on the findings of this study, we believe that the treatment of primary and/or recurrent Dupuytren's contracture with CCH is a safe and less invasive alternative to fasciectomy in the era of telemedicine. CCH treatment requires no suture removal, which allows the ability to assess motion virtually, and the potential consequences of CCH treatment such as skin tears can be assessed and managed conservatively. In the veteran and active duty population, CCH can facilitate faster recovery and return to service. Strengths of this study include a large series of veteran populations with longitudinal follow-up to determine treatment efficacy for primary Dupuytren's contracture and recurrence. Limitations include a smaller sample size compared to previous trials, a lack of standardized follow-up, and the retrospective nature of our study that prohibits randomization to compare outcomes between CCH treatment and fasciectomy efficacy over time. Directions for future research include stratification of patients by joint and specific digit involvement as well as comparison with percutaneous needle fasciotomy, another minimally invasive technique that could benefit the veteran population at increased risk for developing Dupuytren's disease.