Safety Of Collagenase Clostridium Histolyticum Research Articles

Outcomes of collagenase Clostridium histolyticum in men with ventral curvatures: an updated series.

The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie's disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. Changes in penile curvature, Peyronie's Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was -25.0° in the ventral cohort vs -24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was -35.0° in the ventral cohort vs -25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie's Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

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.

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.

Efficacy and safety of collagenase Clostridium histolyticum in Peyronie’s disease following a modified treatment protocol

IntroductionCollagenase Clostridium histolyticum (CCH) is the only approved treatment for conservative management of Peyronie’s disease (PD) that has demonstrated efficacy and safety in clinical trials. However, as the standard treatment protocol is time and resource consuming, we are introducing a new CCH treatment protocol with a more cost-effective profile. Our goal is to evaluate its efficacy and safety. Materials and methodsWe included patients with PD in stable phase, with curvatures of 30–90°. Ventral curvatures and complex deformities were excluded. The treatment protocol consists of a full dose of CCH injected along the PD plaque, forming two lines of four injections. Patients were educated in daily penile modeling activities. The need for a new treatment cycle, up to a maximum of 8 cycles or until the 30° curve was decreased, was reevaluated every 4 weeks. Changes in curvature and number of cycles were recorded to evaluate the efficacy. Regarding safety evaluation, treatment-related adverse events (TRAEs) were recorded, including rupture of the corpora cavernosa, penile hematoma, hematuria, and local infection. ResultsThirty-one patients were treated under the modified protocol. The mean initial curvature was of 49.84 (±15.83)°. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42)° and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25)°. Most patients required one (19.4%) or two (54.8%) injections. No patient presented TRAEs. ConclusionsThe results suggest that the modified CCH treatment protocol is effective and safe, but more studies should be carried out to optimize the current standard protocol.

Long-term Curvature Deformity Characterization in Men Previously Treated With Collagenase Clostridium Histolyticum for Peyronie's Disease, Subgrouped by Penile Plaque Calcification

ObjectiveTo examine the long-term (5-year) efficacy and safety of collagenase clostridium histolyticum (CCH) therapy in men with Peyronie's disease and varying degrees of plaque calcification. Materials and MethodsCCH-treated adult men from the 12-month Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I/II or 9-month open-label studies were eligible. Degree of plaque calcification (no calcification, noncontiguous stippled calcification, or calcification that did not interfere with CCH injection) was determined by penile x-ray or ultrasound. Penile curvature deformity and Peyronie's Disease Questionnaire responses were assessed annually for up to 5 years, with ≥6 months between consecutive visits. ResultsFor no calcification group, from baseline to last (Reference) visit during the prior studies (n = 160), mean penile curvature improved by 20.9° ± 16.3° (39.3%) with CCH. Similar improvements with CCH from baseline to Reference were observed in stippled calcification (n = 27; improvement of 24.1° ± 20.2° [42.7%]) and calcification (n = 27; improvement of 21.7° ± 14.8° [43.3%]) subgroups. At Year 5 follow-up in no calcification group (n = 119), an additional 10.0% improvement in mean penile curvature vs Reference (4.3°) occurred. Penile curvature improvements seen at Reference in stippled calcification and calcification groups were maintained through Year 5. Additional numeric improvements in 3 Peyronie's Disease Questionnaire domains were observed at Year 5 visit vs baseline scores. No long-term safety issues were identified. ConclusionThis first report of long-term (5-year) CCH clinical trial outcomes in a population with penile plaque calcification demonstrates that nonsurgical intralesional CCH therapy is an appropriate Peyronie's disease treatment in men with penile plaque calcification that is stippled or does not impede CCH injection.

Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute Phase Peyronie's Disease: A Multi-institutional Analysis

To study, in a multi-institutional setting, the efficacy/safety outcomes in acute phase Peyronie's disease (PD) of multiple high-volume centers employing CCH to treat PD, which is defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis. It is a chronic condition that afflicts 3%-13% of the US male population. There is no current multi-institutional research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD. Retrospective data were collected for consecutive patients with PD who underwent treatment with CCH between April 2014 and March 2018 at 5 institutions. 918 patients were included. Patients with duration of PD no longer than 6 months at presentation qualified as being in the acute phase of PD. Main outcomes of interest include the change in curvature after receiving CCH therapy, and frequency of serious treatment-related adverse events. Successful improvement in curvature is defined as an at least 20% decrease in penile curvature from baseline after CCH therapy. A total of 918 patients were included in the analysis, of which 134 (14.6%) qualified as acute phase PD (group 1) and the remaining 784 (85.4%) qualified as stable phase (group 2). Mean duration of PD was 4.44 ± 1.68 months for group 1, and 40.8 ± 61.2 months for group 2. There was no significant difference in final change in curvature between acute and stable phase of PD (13.5° vs 15.6°, P = .09). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (16 patients, 11.9%) and the stable phase (77 patients, 9.8%; P=.44). In our multivariate analysis, only number of CCH cycles received was predictive of improvement of curvature. This large multi-institutional analysis confirms that CCH therapy is as safe and efficacious in acute phase PD as it is in stable phase PD.

Treatment-related Outcomes for Patients With Atypical Peyronie's Disease Using Xiaflex Injections

OBJECTIVETo evaluate the efficacy and safety of collagenase Clostridium histolyticum (CCH) for the management of penile deformities in patients presenting with different categories of atypical Peyronie's disease (PD). METHODSWe conducted a retrospective review of charts of patients who presented to a men's health clinic with atypical PD between October 2016 and June 2019. We included patients in the stable phase of the disease, had completed a penile duplex Doppler ultrasound before any intervention, and proceeded with CCH treatment. Gathered data included patient demographics, treatment details, outcomes, and complications. Outcomes collected were both quantitative (curvature assessments) and qualitative using the symptom bother domain (last 6 questions; Q10 to Q15) of the Peyronie's Disease Questionnaire. RESULTSTwenty-one men with stable PD underwent CCH inject therapy after penile duplex Doppler ultrasound. The mean number of injections was 8.4 (standard deviation [SD] = 3.3), and the mean follow-up was 20.5 months (SD = 5.9). The overall mean change in penile curvature was −19.2° ± 8.3°, which corresponded to a −39% ± 13% improvement in curvature (P = .0079). In men who presented with an indentation or hourglass deformity, 11 of 17 (64%) were satisfied and reported subjective improvement in narrowing/indentation after receiving CCH injections. The average composite symptom bother domain of the Peyronie's Disease Questionnaire decreased by 6.7 (P = .0029). CONCLUSIONOur results suggest that CCH appears to be safe and provide significant clinical improvements in men presenting with atypical PD.

Review of Intralesional Collagenase Clostridium Histolyticum Injection Therapy and Related Combination Therapies in the Treatment of Peyronie's Disease (an Update).

Collagenase Clostridium histolyticum (CCH) is an injectable agent used to treat Peyronie's disease (PD) by enzymatically degrading the interstitial collagen in plaques. CCH has been administered via multiple treatment protocols, in combination therapies, to patients with varying curvatures and in both the acute and stable phases of this condition. To review the current literature and provide an update on CCH as an injectable therapy for PD, as a singular therapy or in conjunction with combination therapies, and its associated complications. We provide a brief background of PD treatments, evaluate CCH efficacy in penile curvature reduction and subjective improvement in a variety of protocols, and compare combination therapies (penile traction, sildenafil), plaque location, and efficacy in both acute and stable diseases. We performed a systematic review of the existing PubMed literature pertaining to CCH injection therapy in the treatment of PD and compared the effectiveness to different treatment modalities. CCH is a safe and effective injectable agent for all curvature directions in both acute and stable PD. It can be used in conjunction with multiple penile modeling techniques, in combination with sildenafil, and following a shortened administration protocol. Moderate to severe treatment-related adverse events occur at a rate of 9% and are typically managed conservatively. Intralesional injections of CCH are FDA approved as a nonsurgical treatment for men with PD. The IMPRESS trials were instrumental in demonstrating the efficacy and safety of CCH and provided a standard protocol for administration. Additional studies are required to optimize treatment protocols and use in combination therapies. Further investigation of patients with ventral curvatures, hourglass deformities, and those in acute phase is needed. Natale C, McLellan D, Yousif A, etal. Review of Intralesional Collagenase Clostridium Histolyticum Injection Therapy and Related Combination Therapies in the Treatment of Peyronie's Disease (an Update). Sex Med 2021;9:340-349.

156 Intralesional Collagenase Clostridium Histolyticum Therapy for Peyronie's Disease is Safe in Patients Continuing Antiplatelet and Anticoagulant Therapy: A Single Center Experience

The initial clinical trials for intralesional collagenase Clostridium histolyticum (CCh) injection therapy for Peyronie’s disease (PD) excluded men on anticoagulant or antiplatelet medications except those on low-dose aspirin. Men with PD who take blood thinners present a challenging clinical scenario due to a lack of evidence regarding the safety of CCh while on anticoagulant or antiplatelet therapy. Blood thinning medications critically prevent cardiovascular mortality, and therefore their suspension for a non-life-threatening condition is problematic. Physicians may want to offer CCh to these patients without discontinuing these drugs, however they face the dilemma of having insufficient evidence of the drug’s safety while on such medication. This study aimed to evaluate safety outcomes among patients continuing anticoagulant and antiplatelet therapy during ongoing intralesional CCh injection treatment for PD. An institutional review board approved database of 187 patients treated with CCh at an academic men’s health practice from January 2016 through April 2019 was reviewed. Data on patient demographics, comorbidities, CCh injection details, use or non-use of blood thinner medications, and adverse events were extracted from the electronic medical record. Rates of hematoma formation, bruising, swelling, and corporal rupture were determined. Univariate statistical analysis compared clinical data and adverse events between men on or off blood thinner medications.

Short-term efficacy and safety of collagenase injection for Dupuytren's contracture: Therapy protocol for successful outcomes in a clinical setting

PurposeTo assess the short-term efficacy and safety of collagenase injection for Dupuytren's contracture and of our post-injection therapy protocol alternative the instruction of phase III studies at clinical setting. MethodsThe retrospective study included 23 fingers of 21 hands of 18 patients for primary metacarpophalangeal (MP) joints and 11 fingers of 10 hands of 10 patients for primary proximal interphalangeal (PIP) joints with Dupuytren's contracture who were treated with 0.58 mg collagenase Clostridium histolyticum (CCH) injections at our hospital consecutively from September 2015 to October 2017. The mean age of the patients was 73.0 years (range, 57–88) for primary MP joints and 70.7 years (61–81) for primary PIP joints. Following standard CCH injection and manipulation on the next day, certified hand surgeons evaluated and treated each patient based on a defined 4-week therapy protocol that consisted of performing finger exercises during the day and wearing static extension splint at night for all cases, and of wearing Capener dynamic splint intervention to address severely contracted PIP joints. We measured the degree of contracture at baseline, immediately, 4 weeks, and 12 weeks after the last manipulation. ResultsMore improvement of contracture was seen in the MP joints than in the PIP joints. For the five fingers severely contracted and treated with Capener splint intervention, the mean passive PIP joint contracture was 62.0° at baseline, 21.0° immediately, further improved to 6.0° by 4 weeks, and maintained 8.0° by 12 weeks after the last manipulation. The adverse events were mild-to-moderate local reactions in the injected hand. ConclusionsThe clinical efficacy and safety of CCH were confirmed in a clinical setting similar to phase III studies. The improvement of 4-week-intervention was maintained at 12 weeks after the last manipulation. Severely contracted PIP joints could benefit from Capener splint intervention.

Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease

BackgroundPeyronie’s disease (PD), defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis, is a chronic condition that afflicts 3% to 13% of the US male population; there is no current research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD. AimTo examine the efficacy and safety of CCH in the treatment of acute-phase PD. MethodsWe retrospectively reviewed the records for all patients treated with CCH for PD from April 2014 through April 2017. Patients who reported penile pain and duration of PD no longer than 12 months at presentation qualified as being in the acute phase of PD. The primary outcomes of interest were final changes in curvature after CCH treatment regardless of the number of CCH cycles received and frequency of treatment-related adverse events. OutcomesParameters of efficacy and safety were compared between acute- and stable-phase PD. ResultsA total of 162 patients were included in the study, of which 36 (22%) qualified as having acute-phase PD (group 1) and the remaining 126 (78%) qualified as having stable-phase PD (group 2). Median duration of PD was 8.5 months (range = 1–12) for group 1 and 18 months (range = 1–492) for group 2. There was no significant difference in final change in curvature between the acute and stable phases of PD (16.7° vs 15.6°; P = .654). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (4 patients, 11%) and the stable phase (12 patients, 10%; P = .778). Clinical ImplicationsCCH therapy is as safe and efficacious in acute-phase PD as it is in stable-phase PD. Strengths and LimitationsThis is the first report that assesses the safety and efficacy of CCH therapy focusing on acute-phase PD. This study was composed of a large cohort of patients receiving CCH therapy in acute- and stable-phase PD. Limitations include bias associated with retrospective studies, a small sample, and a single-center setting. ConclusionsAlthough CCH is not clearly indicated for treatment during the acute phase of PD, these results suggest that CCH use during this phase can be effective and safe. There was no statistically significant difference in final change in curvature or treatment-related adverse events after CCH therapy delivered between the acute and stable phases of PD.Nguyen HMT, Anaissie J, DeLay KJ, et al. Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease. J Sex Med 2017;14:1220–1225.

Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial

BackgroundTo determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules.MethodsIn this 8-week, double-blind trial, palpable palmar nodules on one hand of adults with Dupuytren disease were selected for treatment. Patients were randomly assigned using an interactive web response system to receive a dose of 0.25 mg, 0.40 mg, or 0.60 mg (1:1:1 ratio) and then allocated to active treatment (CCH) or placebo (4:1 ratio). All patients and investigators were blinded to treatment. One injection was made in the selected nodule on Day 1. Caliper measurements of nodule length and width were performed at screening and at Weeks 4 and 8. Investigator-reported nodular consistency and hardness were evaluated at baseline and Weeks 1, 4, and 8. Investigator-rated patient improvement (1 [very much improved] to 7 [very much worse]) and patient satisfaction were assessed at study end.ResultsIn the efficacy population (n = 74), percentage changes in area were significantly greater with CCH 0.40 mg (−80.1%, P = 0.0002) and CCH 0.60 mg (−78.2%, P = 0.0003), but not CCH 0.25 mg (−58.3%, P = 0.079), versus placebo (−42.2%) at post-treatment Week 8. Mean change in nodular consistency and hardness were significantly improved with CCH versus placebo at Weeks 4 and 8 (P ≤ 0.0139 for all). At Week 8, investigator global assessment of improvement was significantly greater with CCH 0.40 mg and 0.60 mg (P ≤ 0.0014) but not statistically significant with CCH 0.25 mg versus placebo (P = 0.13). Most patients were “very satisfied” or “quite satisfied” with CCH 0.40 mg and 0.60 mg. Contusion/bruising (50.0% to 59.1%) was the most common adverse event with CCH treatment.ConclusionIn patients with Dupuytren disease, a single CCH injection significantly improved palmar nodule size and hardness. The safety of CCH was similar to that observed previously in patients with Dupuytren contracture.Trial registrationClinicalTrials.gov identifier: NCT02193828. Date of trial registration: July 2, 2014 to December 5, 2014

Racial variations in response to intralesional collagenase clostridium histolyticum in men with Peyronie's disease.

BackgroundAn examination of potential racial variations between Caucasian American (CA) and African American (AA) men in the efficacy and safety of collagenase clostridium histolyticum (CCH) in the treatment of Peyronie’s disease (PD).MethodsWe retrospectively reviewed the records for all patients treated with CCH for PD between 04/2014 and 05/2017. Patients were divided into two groups based on their self-reported race. The primary outcomes of interest were final change in curvature after CCH treatment regardless of number of CCH cycles received, and frequency of treatment-related adverse events (TRAEs).ResultsA total of 159 patients were included in the study, of which 146 (91.8%) were CA while 13 (8.2%) were AA. Mean duration of PD was 28.3 months for CA patients and 16.8 months for CA patients (P=0.436). There was no significant difference in final change in curvature CA and AA patients (15.9° vs. 13.1° respectively, P=0.445). There was no statistically significant difference in frequency of TRAEs between CA patients (17, 12%) and AA patients (0, 0%) (P=0.208).ConclusionsAlthough racial variations in efficacy and safety of CCH in patients with PD have not been addressed in the literature, preliminary results from our study suggest that CCH therapy may be equally efficacious and safe in both CA and AA men. There was no statistically significant difference in final change in curvature, International Index of Erectile Function (IIEF) scores, penile length, or TRAEs after CCH treatment between CA and AA patients.

Safety and effectiveness of collagenase clostridium histolyticum in the treatment of Peyronie's disease using a new modified shortened protocol.

To evaluate the efficacy and safety of collagenase clostridium histolyticum (CCH; Xiapex® , Xiaflex® ) in the treatment of Peyronie's disease (PD) using a new modified treatment protocol that aims at reducing the number of injections needed and reducing patient visits, thus reducing the duration and cost of treatment. A prospective study of 53 patients with PD who had treatment with CCH at a single centre using a new modified protocol. The angle of curvature assessment after an intracavernosal injection of prostaglandin E1, the International Index of Erectile Function (IIEF) and Peyronie's Disease Questionnaire (PDQ) were completed at baseline and at week 12 (4 weeks after the last injection). The Global Assessment of Peyronie's disease (GAPD) questionnaire was completed at week 12. Under a penile block of 10 mL plain lignocaine 1%, a total of three intralesional injections of CCH (0.9 mg) were given at 4-weekly intervals using a new modified injection technique. In between injections patients used a combination of home modelling, stretching and a vacuum device on a daily basis to mechanically stretch the plaque. Investigator modelling was not performed. The mean (range) penile curvature at baseline was 54 (30-90)°. Of the 53 patients in the study, 51 patients (96.2%) had an improvement in the angel of curvature by a mean (range) of 17.36 (0-40)° or 31.4 (0-57)% from baseline after three CCH injections. The final mean (range) curvature was 36.9 (12-75)° (P < 0.001). There was an improvement in each of the IIEF questionnaire domains, all three PDQ domains and the GAPD. CCH was well tolerated by all patients with only mild and transient local adverse events. The new shortened protocol using CCH treatment is safe, effective, and cost efficient. The results of using only three CCH injections according to this modified protocol are comparable to those of the clinical trials that used eight CCH injections.

Safety Profile of Collagenase Clostridium Histolyticum Stratified by Degree of Penile Curvature in Patients With Peyronie Disease

To examine the safety of collagenase clostridium histolyticum (CCH) in adult men with penile curvature deformity <30°. CCH is indicated for treatment of Peyronie disease in adult men with palpable plaque and a penile curvature deformity ≥30° at start of therapy; however, during treatment, patients may receive CCH injections when penile curvature deformity is <30°. Patients who received ≥2 CCH treatment cycles in 2 phase 3 studies (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II) were included. All patients had penile curvature ≥30° at the beginning of treatment and could receive up to 4 treatment cycles. The rate and number of treatment-related adverse events (TRAEs) with CCH treatment were compared between patients with penile curvature deformity ≥30° and penile curvature <30°. The number of CCH treatment cycles included in the current analysis totaled 1204 and 289 cycles in patients with penile curvature deformity ≥30° and <30°, respectively. The incidence of most TRAEs was similar between groups. Rates of penile swelling (21.1% vs 14.5%, P = .007), penile hemorrhage (12.8% vs 8.9%; P = .046), and skin hyperpigmentation (1.0% vs 0.1%; P = .025) were significantly higher in the <30° group. The occurrence of serious TRAEs was similar between groups. No clinically meaningful differences were observed with TRAE rates when CCH injections were administered at penile curvature deformity ≥30° vs CCH injections at penile curvature deformity <30°. These findings highlight the safety of continued CCH injections for patients who have achieved penile curvature deformity <30° after an initial treatment cycle of CCH.

MP56-04 SAFETY AND EFFECTIVENESS OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN THE TREATMENT OF PEYRONIE'S DISEASE USING A NEW SHORTENED PROTOCOL

You have accessJournal of UrologySexual Function/Dysfunction: Peyronie’s Disease II1 Apr 2017MP56-04 SAFETY AND EFFECTIVENESS OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN THE TREATMENT OF PEYRONIE'S DISEASE USING A NEW SHORTENED PROTOCOL Amr Abdel Raheem, Marco Capece, Ayo Kaljaiye, Amr Mobasher, Giulio Garaffa, Nim Christopher, and David Ralph Amr Abdel RaheemAmr Abdel Raheem More articles by this author , Marco CapeceMarco Capece More articles by this author , Ayo KaljaiyeAyo Kaljaiye More articles by this author , Amr MobasherAmr Mobasher More articles by this author , Giulio GaraffaGiulio Garaffa More articles by this author , Nim ChristopherNim Christopher More articles by this author , and David RalphDavid Ralph More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1757AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Collagenase clostridium histolyticum (CCH)is the only licensed product for the treatment of Peyronie's disease (PD). The clinical safety and efficacy of CCH in PD was shown in two large clinical trials; IMPRESS I & II. The aim of this study is to evaluate the efficacy and safety of CCH in the treatment of PD using a new modified treatment protocol which aims at reducing the number of injections needed and reducing patient visits, thus reducing the cost and duration of treatment. METHODS A prospective study of 50 patients with PD who are having treatment with CCH at a single centre using a new modified protocol. Patients with active disease, complete plaque calcification or ventral curvature were excluded. The angle of curvature assessment after an intra-cavernosal injection of PGE1, IIEF and Peyronie's disease questionnaire (PDQ) were performed at baseline and at week 12. The global assessment of PD questionnaire was performed at week 12. Under a penile block of 10ml of lignocaine 1%, a total of 3 intra-lesional injections of CCH (0.9mg) were given at 4 weekly intervals using a new modified injection technique. CCH was injected in the plaque along 3 lines separated by 2mm at the apex of the curvature with the penis in the flaccid state. Six patients requested an additional 3 injections to have a total of 6 injections. In between injections patients used a combination of home modelling, stretching and a vacuum device on a daily basis in order to mechanically stretch the plaque. Investigator modelling was not performed. RESULTS So far 46 patients have completed treatment; all had 3 injections. At baseline, the mean penile curvature was 53.8°(30°-90°). Overall, 44 patients (95.6%) had an improvement in curvature with a mean value of 17.08° (0°-40°) or 30.8% from baseline (0-57%) after 3 injections. The end mean curvature for all patients after 3 injections was 37° (12°- 75°; p≤ 0.001). There was a statistically significant improvement in each of the IIEF questionnaire domains, all 3 PDQ domains and the global assessment of PD questionnaire. The 6 patients who had 3 more injections continued to have additional curvature improvement, mean 19.8° (0°-40°). CCH was well tolerated by all patients with only mild and transient local side effects. The results of this study with only 3 CCH injections are comparable to those of the clinical trials using 8 CCH injections. With the new protocol, only 4 patient visits are needed including assessments versus 14 visits as per trial protocol. CONCLUSIONS The new shortened protocol for CCH in PD is safe, effective and cost efficient. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e756 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Amr Abdel Raheem More articles by this author Marco Capece More articles by this author Ayo Kaljaiye More articles by this author Amr Mobasher More articles by this author Giulio Garaffa More articles by this author Nim Christopher More articles by this author David Ralph More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

AB009. Xiaflex as a treatment for Peyronie’s disease

Peyronie disease can be physically and psychologically devastating for subjects and their partners. Collagenase Clostridium histolyticum (CCh), a purified mixture of AUX-I and II collagenases, is an intralesional, minimally invasive intervention with evidence of tolerability and efficacy in subjects with PD and is approved by the United States Food and Drug Administration for use in adults who have Peyronie Disease and Dupuytren contracture. The Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies (IMPRESS) I and II examined the clinical efficacy and safety of CCh intralesional injections in subjects with Peyronie disease. Primary outcomes in these identical phase 3 randomized, double blind, placebo controlled studies included the percent change in penile curvature and the change in the Peyronie disease questionnaire (PDQ) symptom bother score from baseline to 52 weeks. IMPRESS I and II examined CCh intralesional injections in 417 and 415 subjects, respectively, through a maximum of 4 treatment cycles, each separated by 6 weeks. Men received up to 8 injections of 0.58 mg CCh, comprising 2 injections per 6 week cycle separated by approximately 24 to 72 hours with subsequent penile plaque modeling within 24 to 72 hours. Men were stratified by baseline penile curvature (30 to 60 vs. 61 to 90 degrees) and randomized to CCh or placebo 2:1 in favour of the former. Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with CCh showed a mean 34% improvement in penile curvature, representing a mean ±SD −17.0±14.8 degree change per subject, compared with a mean 18.2% improvement in placebo treated men, representing a mean −9.3±13.6 degree change per subject (P<0.0001). The mean change in PDQ symptom bother score was significantly improved in treated men vs men on placebo (−2.8±3.8 vs. −1.8±3.5, P=0.0037). Three serious adverse events (corporeal rupture) were surgically repaired. IMPRESS I and II support the clinical efficacy and safety of CCh for the physical and psychological aspects of Peyronie disease.

Dupuytren Contracture Recurrence Following Treatment With Collagenase Clostridium Histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data

Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study was a 5-year noninterventional follow-up study to determine long-term efficacy and safety of collagenase clostridium histolyticum (CCH) treatment for Dupuytren contracture. Patients from previous CCH clinical studies were eligible. Enrolled patients were evaluated annually for contracture and safety at 2, 3, 4, and 5 years after their first injection (0.58 mg) of CCH. In successfully treated joints (≤ 5° contracture following CCH treatment), recurrence was defined as 20° or greater worsening (relative to day 30 after the last injection) with a palpable cord or any medical/surgical intervention to correct new/worsening contracture. A post hoc analysis was also conducted using a less stringent threshold (≥ 30° worsening) for comparison with criteria historically used to assess surgical treatment. Of 950 eligible patients, 644 enrolled (1,081 treated joints). At year 5, 47% (291 of 623) of successfully treated joints had recurrence (≥ 20° worsening)-39% (178 of 451) of metacarpophalangeal and 66% (113 of 172) of proximal interphalangeal joints. At year 5, 32% (198 of 623) of successfully treated joints had 30° or greater worsening (metacarpophalangeal 26% [119 of 451] and proximal interphalangeal 46% [79 of 172] joints). Of 105 secondary interventions performed in the successfully treated joints, 47% (49 of 105) received fasciectomy, 30% (32 of 105) received additional CCH, and 23% (24 of 105) received other interventions. One mild adverse event was attributed to CCH treatment (skin atrophy [decreased ring finger circumference from thinning of Dupuytren tissue]). Antibodies to clostridial type I and/or II collagenase were found in 93% of patients, but over the 5 years of follow-up, this did not correspond to any reported clinical adverse events. Five years after successful CCH treatment, the overall recurrence rate of 47% was comparable with published recurrence rates after surgical treatments, with one reported long-term treatment-related adverse event. Collagenase clostridium histolyticum injection proved to be an effective and safe treatment for Dupuytren contracture. For those receiving treatment during follow-up, both CCH and fasciectomy were elected options. Therapeutic II.

Efficacy and Safety of Collagenase Clostridium Histolyticum in the Treatment of Proximal Interphalangeal Joints in Dupuytren Contracture: Combined Analysis of 4 Phase 3 Clinical Trials

To examine the results of proximal interphalangeal (PIP) joint contractures from 4 phase 3 clinical trials of collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture. Patients enrolled in Collagenase Option for Reduction of Dupuytren I/II and JOINT I/II with one or more PIP joint contractures (20° to 80°) received CCH 0.58 mg/0.20 mL or placebo (Collagenase Option for Reduction of Dupuytren I/II only) injected directly into a palpable cord. The percentage of PIP joints achieving clinical success (0° to 5° of full extension), clinical improvement (50% or more reduction in baseline contracture), and range of motion improvement at 30 days after the first and last CCH injections was assessed. The PIP joint contractures were classified into low (40° or less) and high (more than 40°) baseline severity. Adverse events were recorded. A total of 506 adults (mean age, 63 ± 10 y; 80% male) received 1,165 CCH injections in 644 PIP joint cords (mean, 1.6 injections/cord). Most patients (60%) received 1 injection, with 24%, 16%, and 1% receiving 2, 3, and 4 injections, respectively. Clinical success and clinical improvement occurred in 27% and 49% of PIP joints after one injection and in 34% and 58% after the last injection. Patients with lower baseline severity showed greater improvement and response was comparable between fingers, as were improvements in range of motion. Adverse events occurring in more than 10% of patients were peripheral edema (58%), contusion (38%), injection site hemorrhage (23%), injection site pain (21%), injection site swelling (16%), and tenderness (13%). This incidence was consistent with data reported in phase 3 trials. Two tendon ruptures occurred. No further ruptures occurred after a modified injection technique was adopted. Collagenase clostridium histolyticum was effective and well tolerated in the short term in patients with Dupuytren PIP joint contractures. Therapeutic II.

Analysis of Efficacy and Safety of Treatment With Collagenase Clostridium histolyticum Among Subgroups of Patients With Dupuytren Contracture

Collagenase Clostridium histolyticum (CCH) injection is a nonoperative treatment of hand contractures from Dupuytren disease. This study assessed the efficacy and safety of CCH in several subgroups of patients with increased surgical risk.Data were pooled from 3 randomized, placebo-controlled, double-blind trials. This analysis included 271 patients with metacarpophalangeal (n = 167) or proximal interphalangeal (n = 104) joint contractures greater than or equal to 20 degrees treated with CCH (0.58 mg collagenase per injection). Subgroups included age, sex, and diabetes status. End points included rate of clinical success (reduction in contracture to 0-5 degrees of normal) and percentage of adverse events.There was no significant difference in clinical success by age, diabetes status, or sex with 63% reaching the end point. There was no difference in adverse events among the subgroups, with peripheral edema, contusion, and injection-site hemorrhage being most common.High-risk subgroups do not demonstrate differences in efficacy or safety with CCH treatment of Dupuytren-related contractures.