Collagenase Clostridium Histolyticum Injection Research Articles

What's New in Hand and Wrist Surgery.

What's New in Hand and Wrist Surgery.

The incidence of surgical intervention in veterans treated with Collagenase clostridium histolyticum.

Peyronie's disease (PD) can be managed with surgery or intralesional injections of Collagenase clostridium histolyticum (CCH) however both are associated with side effects and variable results. It is unclear how many patients elect to undergo additional surgical correction after CCH. To answer this, we analyzed the Department of Veterans Affairs Informatics and Computing Infrastructure (VINCI) software. We performed a retrospective analysis over a 5-year period for patients with PD, at least one injection of CCH and surgical CPT codes. In total, 17,646 patients with PD were analyzed with 1541 treated with CCH. Only 51 (3.3%) were treated with secondary surgical intervention after CCH. Three main surgical procedures were performed: penile plication (51%), penile prosthesis (29%) and plaque excision and grafting (20%). Of the 51 men who underwent surgical corrections post CCH, the most common reason was lack of response/residual curvature (62.8%), followed by ED (29.4%). Previous literature shows that CCH was effective for only 60.8% of patients, potentially leaving the remaining in need of additional treatment. Despite this we found that only 3.3% received secondary therapy in the VA medical system, with residual curvature being the most common reason.

Dose- and time-dependent effects of collagenase clostridium histolyticum injection on transverse carpal ligament elastic modulus and thickness in vitro.

A potential treatment for carpal tunnel syndrome is to biochemically alter the mechanical properties of the transverse carpal ligament (TCL) through Collagenase Clostridium Histolyticum (CCH) injection. The purpose of this study was to determine the time- and dose-dependent effects of CCH injection on TCL elastic modulus and thickness. Nine TCLs were dissected from cadaveric hands for this study. CCH doses of 50U, 100U, 150U, 200U, and 250U were injected into five points on the TCL, respectively. B-mode and shear wave elastography images were taken of each injection point using robot-assisted ultrasound imaging immediately after injection, as well as 2, 4, 6, 8, and 24 hours after injection. TCL thickness and mean shear wave speed were measured for each CCH dose at each time point. CCH doses of 200U and 250U decreased shear wave speed by 18.70% and 30.01% (p<0.05), respectively, after 24 hours. CCH doses of 150U, 200U, and 250U decreased TCL thickness by 7.28%, 10.97%, and 14.92%, respectively, after 24 hours (p<0.05). Our findings suggest that CCH injection may be effective in degrading TCL tissue, with higher doses of CCH resulting in greater tissue degradation up to 24 hours after injection.

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

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. 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). 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. 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 November2016. Therapeutic IV.

Short-term efficacy and adverse effects of collagenase clostridium histolyticum injections, percutaneous needle fasciotomy and limited fasciectomy in the treatment of Dupuytren’s contracture: a network meta-analysis of randomized controlled trials

AimsDupuytren’s contracture (DC) is a chronic debilitating fibroproliferative disorder.Common treatment options include collagenase clostridium histolyticum injections (CI), percutaneous needle fasciotomy (NF) and limited fasciectomy (LF). Superiority of one specific treatment remains controversial. This study aims to assess the short-term efficacy and safety of CI, NF, and LF for the treatment of DC.MethodsWe included randomized controlled trials of CI compared with placebo, NF and LF for patients with DC. PubMed, Embase and the Cochrane Library were searched from inception to August 2021. Contracture reduction rates in treated joints (within 0–5° of full extension within 30 days), relative reduction in total passive extension deficit (TPED), occurrence of one or more adverse events and number of treatment-related adverse events per patient were the outcomes of interest. The Cochrane risk-of-bias tool was employed for quality assessment of the studies. A network meta-analysis was performed using MetaXL.ResultsNine studies met our inclusion criteria (n = 903). Overall, risk bias was mixed and mostly low. Short term TPED reduction achieved with LF was superior compared to CI and NF. Although CI achieved greater TPED reduction compared to NF, it was associated with the highest risk of overall adverse effects. The analyzed data was limited to a maximum three-year follow-up period and therefore insufficient for long-term outcome evaluation.ConclusionsIn DC, LF may be able to provide patients with severe disease, superior flexion contracture release postoperatively. CI is a valid treatment alternative to NF, however the higher risk of overall adverse effects must be considered. The quality-of-evidence is limited due to short-term follow-up periods and a lack of standardized definitions of complications and adverse events.

Dupuytren Disease: A Retrospective Cohort Study Comparing Collagenase Injection and Percutaneous Needle Fasciotomy.

Background:Collagenase Clostridium histolyticum (CCH) injection and percutaneous needle fasciotomy (PNF) are minimally invasive procedures aiming to relieve Dupuytren disease (DD) by disrupting the cord and restoring the normal functionality of the hand. The purpose of this study is to compare the outcomes and recurrence rates for treatment of DD in the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints with either collagenase or percutaneous needle at 3-year follow-up. Moreover, we aim to determine the role of these therapeutic modalities and their impact on hand functionality and quality of life.Methods:In this retrospective analysis, we compare treatment outcomes in 35 patients, of whom 22 were treated with PNF and 13 with CCH injection.Results:The mean outcome in contracture degrees at 3-year follow-up was 9 degrees for MCP joints for both treatment groups, 34 degrees for PNF, and 28 degrees for CCH for PIP joints. There was no statistical significance between the treatment groups in MCP joints (P = 0.786) or in PIP joints (P = 0.474). Contracture recurrences were similar in PIP joints of both groups and greater in MCP joints in the CCH group compared to PNF. The Disabilities of the Arm, Shoulder, and Hand and the Unité Rhumatologique des Affections de la Main scores showed a reduction in impairment in both groups without significant differences between the two groups.Conclusions:The results of this study show that PNF appears to be as effective and minimally invasive as CCH injection, but at significantly lower cost. Considering these factors, the authors prefer and recommend the use of PNF over CCH.

Collagenase Clostridium histolyticum Treatment Improves Degree of Curvature in Peyronie’s Disease with Calcified Plaques

BackgroundPeyronie’s disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional collagenase Clostridium histolyticum (CCh) is effective in noncalcified PD; however, its effectiveness in calcified PD is not well characterized. ObjectiveTo assess curvature improvement in calcified PD plaques treated with CCh. Design, setting, and participantsWe prospectively evaluated men with calcified PD electing CCh treatment at our institution from October 2018 to November 2020. We assessed curvature with artificial erection and goniometer before and at least 3 mo after treatment. We classified the type of plaque calcification based on ultrasound. InterventionIntralesional CCh. Each treatment cycle consisted of two CCh injections (0.58 mg) into the plaque at the point of maximal penile curvature. The second injection was performed 72 h to 1 wk later, after which participants began modeling. All men were intended to receive a total of eight injections in four cycles, each 6 wk apart. Outcome measurements and statistical analysisChange in penile curvature after CCh was measured. We assessed for differences in outcomes based on the number of injections and type of calcification. Unless otherwise specified, data are presented as medians (interquartile range). Results and limitationsSixty men with calcified PD elected CCh; 47 had complete follow-up data. Thirty-nine men completed treatments with eight injections, while the remaining discontinued after a median of five (four to six) injections. There was no difference in response between type 2 and type 3 plaques. Curvature significantly improved by 17.5° (37.5–10.0°) in patients who completed treatment and by 15.0° (20.0–0.0°) in those who discontinued. Limitations include a small sample. ConclusionsMen with calcified PD plaques improve with CCh treatment and show similar improvements regardless of calcification type. Patient summaryIn this study, we evaluated the efficacy of collagenase Clostridium histolyticum (CCh) treatment in calcified Peyronie’s disease (PD) plaques. We found that treatment in calcified plaques demonstrated significant improvement in curvature and the grading of calcification did not impact the degree of curvature improvement. We conclude that participants with calcified PD plaques can benefit from nonsurgical CCh treatment.

Improvement in the ability to have sex in patients with Peyronie's disease treated with Collagenase Clostridium histolyticum.

To describe the results of intralesional Collagenase Clostridium histolyticum (CCH) treatment in patients with Peyronie's disease (PD) in real-world setting. PD is characterized by curvature of the erect penis caused by fibrotic tissue in the tunica albuginea. Patients with stable PD and curvature of 30° to 90° were prospectively enrolled. CCH injections were initially given using a scheme of four cycles of two injections within 48-72 h every 6 weeks. Later using a modified scheme of three injections every 4 weeks, combined with a vacuum erection device (VED) twice daily. All patients were requested to take pictures of the erect penis prior to and following treatment, from above and laterally. Curvature was measured by three independent researchers based on the provided pictures using a goniometer. Furthermore, patients filled in the Peyronie Disease Questionnaire-NL (PDQ-NL) and Patient Reported Outcome Measurement (PROM). Sixty-three patients were included, mean age was 56.0years (range 39-70) and mean reduction in curvature 20.6° (SD 10.2, range 5-49); 74.5% of the patients were able to have penetrating sex again following treatment, compared with 41.2% prior to treatment. According to the PROM questions, sexual improvement was seen in 66.7% of patients. The satisfaction rate was 6.8 (SD 1.8). All patients save two recommend treatment. Intralesional treatment with CCH in men with PD leads to a mean curvature improvement of 20.6°. Following treatment, 74.5% of men were able to have sexual intercourse and 54.9% of the couples were satisfied with their sex life. No major complications occurred in the patients treated with CCH. CCH is not available in Europe anymore despite good results.

Improved Peyronie's Disease Curvature Outcomes Using a Novel Collagenase Administration Protocol

To report outcomes of a novel collagenase clostridium histolyticum (CCH) injection protocol. A prospective, sequential database was maintained of all Peyronie's men undergoing CCH injections since 2015. Our protocol has evolved to include changes with injection technique, timing, aggressive modeling/traction, and wrapping. Results of the "traditional" and "novel" techniques were compared using two definitions: "most recent" assessment and final assessments among men who "completed eight (injections) or were satisfied." A total of 509 men underwent greater than or equal to 1 CCH series (traditional, n=280; novel n=229). Baseline demographic/clinicopathologic characteristics were similar between groups. Results demonstrated significantly greater curve improvements with the novel technique ("most recent" median 30° vs 20° or 46% vs 28%; "completed eight or satisfied" 34° vs 20° or 58% vs 30%). Using the "completed eight or satisfied" definition, 94% vs 66% of men achieved greater than or equal to 20% improvement (odds ratio 7.6), and 60% vs 24% achieved greater than or equal to 50% improvements (odds ratio 5.0) in the novel cohort (all P < .0001). Importantly, the International Index of Erectile Function Erectile Function Domain score was unchanged, and subjective erectile function (50% vs 5%, P < .0001) and sensation improved (17% vs 8% improved, P=.01) with the new protocol. The novel cohort also reported higher rates of surgery prevention (53% vs 18%), restored/facilitated penetration (57% vs 21%), and hematomas (56% vs 26%), necessitating changes to wrapping procedures (all P < .0001). Use of the novel CCH protocol results in significant improvements with curvature without negatively impacting erectile function or sensation. Given its specialized nature, it is not recommended for low-volume CCH injectors.

The efficacy and safety of intralesional injection of collagenase Clostridium histolyticum for Peyronie's disease: A meta-analysis of published prospective studies.

Background: Peyronie’s disease (PD) is a progressive fibrotic disorder of the penis that is adverse to men’s health. Currently, effective and reliable non-surgical options for PD are limited. Since the Food and Drug Administration (FDA) approved it in 2013, intralesional injection of collagenase Clostridium histolyticum (CCH) became the only licensed treatment for PD. This meta-analysis aims to evaluate the clinical efficacy and safety of CCH in treating PD, predominantly based on post-FDA studies. Methods: The primary outcome was clinical efficacy evaluated by the percentages of improvement in penile curvature (PC) and Peyronie’s disease symptom bother score (PD bother score). The secondary outcome was the safety assessed by treatment-related adverse events (TRAEs). Heterogeneity was assessed by Cochran’s Q and I 2 tests. Sensitivity and subgroup analyses were performed to explore the source of heterogeneity. Funnel plots and Egger’s test were used to evaluate the publication bias. Results: A total of 11 studies with 1,480 intentions to treat (ITT) population were included. The pooled effect of the improvement of PC was 35% (95% CI: 0.33–0.38), and the pooled improvement of the PD bother score was 41% (95% CI: 0.37–0.45). No heterogeneity was found at the pooled improvement of PC (p = 0.845, I 2 = 0.00%). Meanwhile, some heterogeneity existed in the pooled improvement of the PD bother score (p = 0.069, I 2 = 43.4%). The pooled effect of TRAEs was 93% (95% CI 0.88–0.97) with significant heterogeneity (p < 0.000, I 2 = 92.3%). Conclusion: The intralesional injection of CCH could significantly improve the penile deformity of PD patients. Meanwhile, CCH appears to ameliorate the PD bother score to some extent and has acceptable clinical safety. Future studies are required to clarify the long-term outcomes of CCH injection in the treatment of PD.

Male Sexual Dysfunction

Male sexual dysfunction is a series of conditions, most notably including erectile dysfunction (ED), Peyronie’s disease (PD), and premature ejaculation (PE), defined by impaired sexual functioning. The prevalence of male sexual dysfunction increases with age and is relatively high with greater than 50% of men aged 40 to 70 describing some degree of erectile dysfunction. Risk factors for male sexual dysfunction include age, diabetes mellitus (DM), cancer, stroke, hypertension, penile trauma, depression, anxiety, and disturbance in central serotonin neurotransmission and 5-HT postsynaptic receptor functioning. Sexual questionnaires including the International Index of Erectile Dysfunction, Sexual Health Inventory for Men, and the Premature Ejaculation Diagnostic Tool are useful in screening for these disorders. Focused history and physical can establish diagnoses. For a condition to be diagnosed as male sexual dysfunction, the patient or their partner must view their sexual functioning as impaired. Treatment of male sexual dysfunction is etiology dependent. For ED, first-line therapy is a phosphodiesterase-5 inhibitor or mental health care for psychogenic ED. More complicated cases may be treated with injections, surgery, or shockwave therapy. PD is either treated with medications for pain management, collagenase clostridium histolyticum injection, corpoplasty, plication, or shockwave therapy. PE may be treated behaviorally or with SSRIs as first line medication.

Patient Insight With Collagenase Treatment for Dupuytren: A Prospective Study

There appears to be controversy regarding differing patient and physician perceptions of adverse effects (AEs) in the treatment of Dupuytren disease with collagenase clostridium histolyticum (CCH). The aim of this study was to compare the number, type, and severity of AEs perceived and reported by patients and by their physician METHODS: To assess AEs following CCH injection in a standardized way, patients were given a list of predefined complications and asked to rate their severity on a 4-point Likert scale ranging from 1 (serious) to 4 (insignificant). Eighty-five patients were included. Patients reported fewer AEs than their physician (mean, 1.48 vs 2.18). There was no agreement between physician- and patient-reported AEs except for skin lacerations, which showed fair agreement (κ= 0.257). Patients and physicians differ in their evaluation of AEs due to CCH treatment in Dupuytren disease. A fair level of agreement was observed for skin lacerations. Greater consensus is needed when defining AEs associated with CCH in the treatment of Dupuytren disease.

The CeCORD-J study on collagenase injection versus aponeurectomy for Dupuytren's contracture compared by hand function and cost effectiveness

This study compared hand function and the cost-effectiveness of treatment between collagenase Clostridium histolyticum (CCH) injection and limited fasciectomy for patients with Dupuytren’s contracture (DC). The CeCORD-J study is a prospective, multicenter, non-randomized controlled, observational study of two parallel groups. Participants were DC patients with multiple affected fingers, including flexion contracture of the proximal interphalangeal (PIP) joint. The primary outcome was the Hand10 score, as a patient-reported outcome measure (PROM). We set secondary outcomes of EQ-5D-5L (QOL) score, degree of extension deficit, and direct cost. Propensity score adjustment was used to balance differences in patient characteristics between groups. Participants comprised 52 patients in the Collagenase group and 26 patients in the Surgery group. There were no significant differences in the Hand10 and QOL scores between the two groups at 26 weeks. Mean direct cost was 248,000 yen higher in the Surgery group than in the Collagenase group. Extension deficit angle of the PIP joint was significantly larger in the Collagenase group at 26 weeks. Although the Collagenase group showed dominance in cost-effectiveness, there was no significant difference between the two groups in hand function at 26 weeks.

Improved Peyronie's Disease curvature outcomes using a more aggressive collagenase technique

ABSTRACT Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie's Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. Objective To report outcomes of a more aggressive CCH injection / traction protocol in men with PD. Methods A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. Results A total of 320 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8 (SD 10.4), with a mean PD duration of 27.8 months (SD 53) and a median baseline composite curvature of 64 degrees (IQR 45-80). Curvature improvements (most recent minus baseline) improved over time, correlating with increased injection experience and implementation of more aggressive traction protocols: 2014-2020 (20 degrees, 29% improvement) vs 2020-mid 2021 (27.8 degrees, 50%, p&amp;lt;0.001). When men were stratified by those who either completed 8 injections or indicated that they were satisfied with outcomes (n=147), median results were more pronounced: 2014-2017 (29% improvement), 2018 (38%), 2019 (47%), 2020-mid 2021 (59%), p&amp;lt;0.01. Conclusions Progressive implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Disclosure Work supported by industry: no.

PD23-01 IMPROVED PEYRONIE’S DISEASE CURVATURE OUTCOMES USING A MORE AGGRESSIVE COLLAGENASE TECHNIQUE

You have accessJournal of UrologyCME1 May 2022PD23-01 IMPROVED PEYRONIE’S DISEASE CURVATURE OUTCOMES USING A MORE AGGRESSIVE COLLAGENASE TECHNIQUE Alissa Tyler, Benjamin Green, Joshua Savage, Klinton Brearton, and Landon Trost Alissa TylerAlissa Tyler More articles by this author , Benjamin GreenBenjamin Green More articles by this author , Joshua SavageJoshua Savage More articles by this author , Klinton BreartonKlinton Brearton More articles by this author , and Landon TrostLandon Trost More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002565.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. The objective of the current study was to report outcomes of a more aggressive CCH injection/traction protocol in men with PD. METHODS: A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. RESULTS: A total of 438 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8, with a mean PD duration of 32 months and a median baseline composite curvature of 64 degrees. Using the definition of most recent curve assessment, mean composite curve improvements were 27.1 degrees (41%) with the new technique vs 17.8 (24.6%, p<0.001). Of men who completed all 8 injections or stopped early due to satisfaction, the mean improvements were 36.4 degrees (59%) vs 19.8 (30.5%, p<0.001). Despite the more aggressive stretching and traction protocol, erectile function was similar to baseline (IIEF-EFD +0.5). CONCLUSIONS: Implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Source of Funding: NA © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e409 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alissa Tyler More articles by this author Benjamin Green More articles by this author Joshua Savage More articles by this author Klinton Brearton More articles by this author Landon Trost More articles by this author Expand All Advertisement PDF DownloadLoading ...

Peyronie's Disease - Outcomes of collagenase clostridium histolyticum injection: A systematic review

ABSTRACT Introduction Peyronie's Disease (PD) is a condition characterized by abnormal and excessive wound repair causing fibrous plaquing of the tunica albuginea. Intralesional (IL) therapies are for patients who prefer to avoid surgical intervention and associated adverse complications. Currently, among available IL injection therapies (Collagenase Clostridium histolyticum (CCh) (Xiaflex, Endo Pharmaceuticals, Dublin, Ireland), verapamil, IFN-a-2b, OnabotulinumtoxinA (Botox) (AbbVie, Chicago, Illinois), Hyaluronic acid). The only FDA approved intralesional treatment option is CCh, which recently expanded its indications for atypical PD. Objective This study aims to review recent literature pertaining to CCh and other intralesional therapies in treatment of PD. Methods A systematic search of literature using exclusively PubMed was performed. There were no specific inclusion or exclusion criteria, however a preference was placed on recent and high impact articles. The review represents many types of studies including randomized control trials, meta-analyses, as well as phase 2 and 3 clinical trials. The use of CCh was compared to other IL therapies and evaluated for efficacy. This included Lastly, CCh use in atypical Peyronie's Disease was assessed for rate of success and complication. Results Recent literature supports the notion that CCh is the most superior IL treatment for typical and atypical PD patients. The capstone CCh study was the IMPRESS trial that showed a 34% reduction in curvature with a mean -17.0 ± 14.8 angle reduction with IL CCh, while men in the placebo saw an average 18.2% decrease in penile bend with a mean -9.3 ± 13.6 degree of change per person (p&amp;lt;0.0001). A shortened protocol for IL CCh treatment offered a 31.4% reduction in curvature while decreasing cost and office visits, potentially increasing patient compliance. Lastly, the literature shows CCh is used most commonly in atypical cases with about 64.8% of patients being treated with CCh – this is probably because of the high efficacy and superb safety profile that it offers. The most serious complications associated with CCh including urethral injury, corporal rupture and penile fracture are rare in all types of PD. Conclusion Since the approval of CCh by the FDA in 2013, it has been a staple in the treatment of PD, and here we report the continued success and superiority of this therapy. CCh is an effective, minimally invasive therapeutic option in most PD populations, however recent changes have made CCh unavailable for commercial use out of the United States, thus impacting many patients who have previous benefited from it. Disclosure Work supported by industry: no.

Outcomes of Collagenase Clostridium Histolyticum in Men with Congenital Penile Curvature

ABSTRACT Introduction Congenital penile curvature is a relatively uncommon condition characterized by penile angulation. Similar to Peyronie's Disease (PD), this condition has historically been managed with various surgical techniques. Given the efficacy of Collagenase Clostridium Histolyticum (CCH) in men with PD, our team has elected to treat men with CPD with CCH injections. Objective To describe outcomes of CPD men treated with CCH injections and to compare against a traditional PD cohort. Methods A prospective database has been maintained of all men undergoing CCH injections by our team since Jan 2014. The specific CCH administration protocol has been modified over time and currently includes combined use of RestoreX traction therapy, sildenafil, 0.9 mg of CCH diluted into 0.7 ml, injections performed at the point of maximal curvature, and aggressive manual modeling. Curvatures were measured in two planes (dorsal and lateral), with the combined measure reported as a composite. Outcomes were reported based on the most recent curvature assessment obtained minus baseline. Men were included if they received at least one series of CCH injections and had at least one baseline and follow-up curvature assessment available. Results A total of 272 men comprised the current cohort, with 23 exhibiting CPD and 249 PD. Mean age was higher in PD men (57.4 vs 38.4, p&amp;lt;0.0001), and mean PD duration was 18 months in PD men. Median baseline curvature was non-statistically higher in PD (65 vs 55 degrees, p=0.06). Baseline curvature directions for PD and CPD, respectively were: dorsal (82% vs 35%, p&amp;lt;0.0001), lateral (58% vs 78%, p&amp;lt;0.05), ventral (11% vs 35%, p&amp;lt;0.01). Following treatment with CCH, median curvature improvement was similar between cohorts, with 20 degrees (IQR 5, 35) for PD and 20 degrees (IQR 5, 30) for CPD, p=0.62. Percentage improvement from baseline was non-statistically higher in PD men (33% vs 29%, p=0.99). Conclusions Treatment of CPD men with CCH is a viable therapeutic option and provides similar benefits to those observed in men with PD. Disclosure No

Eight injections of Collagenase Clostridium Histolyticum May Be Effective in Calcified Plaques

ABSTRACT Introduction Peyronie's disease (PD) is the result of abnormal tissue healing in the tunica albuginea resulting in an inelastic plaque. In some instances, plaques will calcify. Several studies question the efficacy of Collagenase Clostridium Histolyticum (CCH) in calcified plaques leading to a belief that calcification is associated with failure of medical treatment and an increased risk of surgical intervention. Our objective is to measure changes in curvature before and after treatment of calcified plaques with CCH. Objective To determine change in curvature of calcified plaques treated with 8 injections of CCH Methods We prospectively evaluated PD plaques using ultrasound in all men presenting with PD starting November, 2018. Plaques were evaluated in the flaccid state and curvature was measured after the injection of intracavernosal Trimix using goniometer. We utilized a standardized system of plaque typing: type 1: thickening of the tunica albuginea without acoustic shadowing, type 2: a moderately calcified plaque with a typical ultrasound shadow, type 3: a severely calcified plaque complete acoustic shadowing. We measured pre and post CCH curvature 6 months after all eight injections using he standard manufacturer protocol. All patients were instructed on home modeling. Paired T-t was used to compare pre and post measurements. Results presented as means± standard deviations. Results We identified 19 men with calcified PD who completed all 8 injections of CCH. Mean age and curvature were 61±7 years and 55±22 degrees. Of the 19 men, 7 had type 3 plaques and 12 had type 2 plaques. There were no differences in patient age however there was a difference in baseline curvature between type 2 and 3 plaques (55±17 vs 75±17 degrees p&amp;lt;0.05). Curvature improved by an average of 25±20 degrees p&amp;lt;0.05. Interestingly, as a group, type 3 plaques improved by 37±23 degrees compared to 18±15 degrees for Type 2, however this difference was not significant Conclusions In our small cohort, 8 injections of CCH appear to be an effective therapy for men with calcified PD plaques. Interestingly, CCH remained effective even in severely calcified PD. A larger study including a comparison of non-calcified PD is needed. Disclosure Yes, this is sponsored by industry/sponsor: ISR from Endo Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals

Collagenase Clostridium Histolyticum Treatment for Peyronie's Disease: Analysis of Outcomes and Cumulative Benefits After Each Injection Cycle

ABSTRACT Introduction The efficacy and safety of collagenase clostridium histolyticum (CCH) for the treatment of Peyronie's disease (PD) were demonstrated in two phase 3, randomized, double-blind, placebo-controlled studies. CCH injections were administered in up to 4 treatment cycles at 6-week intervals; each cycle included two injections 1-3 days apart. Objective To evaluate incremental changes in penile curvature over the course of CCH treatment in men with PD. Methods A post hoc analysis was conducted using pooled data from the 2 placebo-controlled trials. Change from baseline and from the previous penile curvature measurement were calculated after each of the 4 treatment cycles (Weeks 6, 12, 18, and 24). For all patients, treatment included penile plaque modeling. For CCH vs placebo, mean percentage change in penile curvature was compared using a two-sample t-test; percentage of patients classified as treatment responders (defined as curvature reduction ≥20%) was compared using Fisher's exact test. Results The population included 832 adult men (CCH [n=551]; placebo [n=281]) who received ≥1 injection of study medication. At baseline, mean ± standard deviation (SD) penile curvature was 50.6±14.7 degrees in the CCH group and 50.4±14.1 degrees in the placebo group. Compared with baseline, the mean ± SD percentage change in penile curvature was -12.8±20.3% for CCH vs -6.2±18.8% for placebo after the first treatment cycle, -22.6±23.5% vs -10.6±23.1% after the second, -29.9±25.0% vs -14.6±24.0% after the third, and -33.1±28.0% vs -16.6±25.5% after the fourth (all P&amp;lt;0.001 vs placebo; Figure 1A). Comparing change from the previous measurement (ie, incremental change from previous treatment cycle [eg, between first and second; second and third, etc]), mean ± SD percentage reduction in penile curvature was 11.1±21.8% vs 5.0±16.4% after the second treatment cycle (P&amp;lt;0.001 vs placebo), 9.6±21.8% vs 3.9±17.0% after the third (P&amp;lt;0.001) and 6.3±23.0% vs 2.0±17.2% after the fourth (P=0.009; Figure 1B). The percentage of patients with ≥20% reduction in penile curvature since the previous measurement (cycle) was 29.9% for CCH group vs 18.3% for the placebo group after the first treatment cycle (P=0.0003), 29.1% vs 16.9% after the second (P=0.0002), 25.2% vs 12.8% after the third (P&amp;lt;0.0001), and 20.2% vs 10.9% after the fourth (P=0.001). For patients with a response after 2 treatment cycles (CCH [n=219]; placebo [n=77]), 40.2% of the CCH-treated patients vs 19.5% of the placebo-treated patients had an additional reduction of ≥20% after completing 4 treatment cycles (P=0.001). In patients with &amp;lt;20% reduction after the initial 2 treatment cycles (CCH [n=205]; placebo [n=168]), 29.8% of patients in the CCH group were classified as treatment responders after completing the fourth injection cycle (versus 20.8% of placebo-treated patients; P=0.057). Conclusions Data support that incremental benefits were obtained from each of the 4 CCH treatment cycles administered to men with Peyronie's disease. Results would suggest benefits with performing a full series of 4 CCH injections, even among men who are initial non-responders. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals Inc. Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals Inc.

Improved Peyronie's Disease Curvature Outcomes Using a More Aggressive Collagenase Technique

ABSTRACT Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie's Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. Objective To report outcomes of a more aggressive CCH injection / traction protocol in men with PD. Methods A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. Results A total of 320 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8 (SD 10.4), with a mean PD duration of 27.8 months (SD 53) and a median baseline composite curvature of 64 degrees (IQR 45-80). Curvature improvements (most recent minus baseline) improved over time, correlating with increased injection experience and implementation of more aggressive traction protocols: 2014-2020 (20 degrees, 29% improvement) vs 2020-mid 2021 (27.8 degrees, 50%, p&amp;lt;0.001). When men were stratified by those who either completed 8 injections or indicated that they were satisfied with outcomes (n=147), median results were more pronounced: 2014-2017 (29% improvement), 2018 (38%), 2019 (47%), 2020-mid 2021 (59%), p&amp;lt;0.01. Conclusions Progressive implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Disclosure No