Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum.

INTRODUCTION: Penile curvature is the most common abnormality that is observed by men with Peyronie's disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients. AIM: To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH. METHODS: We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements. OUTCOMES: Degrees of the curvature changes between the baseline and after the cycles of CCH. RESULTS: A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7). CLINICAL IMPLICATIONS: We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment. STRENGTHS AND LIMITATIONS: This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled. CONCLUSION: Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees. Flores JM, Nascimento B, Punjani N, et al. Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum. J Sex Med 2022;19:1680-1686.

Predictors of Pursuing Intralesional Xiaflex in Peyronie's Disease Patients.

BACKGROUND: Intralesional collagenase such as Xiaflex (ILX) has become a standard treatment for Peyronie's disease (PD). Many robust studies have demonstrated its clear efficacy in the treatment algorithm. AIM: To examine predictors of the patient decision to pursue ILX in PD patients. METHODS: The study included PD patients (i) with stable disease (ii) who had doppler duplex ultrasonography (DUS) at least 6 months prior to analysis date and (iii) did not choose an operation. All patients received a standard discussion regarding treatment options, specifically, observation, ILX and penile reconstructive surgery (plication, plaque incision and grafting, implant surgery). Patients who opted to use ILX were compared to those who opted against it. Comorbidity, demographic and PD characteristics were recorded at the initial PD visit. All patients completed three validated questionnaires including the PD questionnaire (PDQ), Self-Esteem and Relationship (SEAR) questionnaire and a depression questionnaire (CES-D). Logistic regression was used to determine predictors of ILX use. OUTCOMES: Predictors of ILX utilization. RESULTS: Four hundred and fifty stable PD men had DUS completed 6 months before to allow sufficient time for treatment decision. Of these, 111 (24.7%) patients had ILX treatment and 339 (75.3%) did not. Mean age, relationship status and pain occurrence were similar between groups, but ILX patients had less bother defined as PDQ ≥ 9 (46.8% vs 53.7%, P = .02). ILX patients had more complex curves (79.3% vs 47.8%, P < .01) and more severe instability (32.4% vs 15.3%, P = .01). ILX patients also had higher PDQ domain scores (Psychological 11.5 ± 6.4 vs 7.5 ± 6.2, P < .01; Pain 6.2 ± 6.0 vs 4.3 ± 5.6, P = .02; and Bother 9.8 ± 4.7 vs 6.6 ± 4.8, P < .01). On univariable statistics, significant bother (OR 2.41, 95% CI 1.36-4.28, P<0.01), complex curvature (OR 4.18, 95%CI 2.52-6.93, P < .01), moderate and/or severe instability (OR 1.98, 95%CI 1.18-3.30, P < .01) and PDQ-Bother scores (OR 1.15, 95%CI 1.08-1.22 P < .01) predicted ILX use. On multivariable analysis, instability (OR 2.58, 95%CI 1.02-6.57, P = .05) and significant bother (OR 1.23, 95%CI 1.04-1.45, P = .01) predicted ILX use. CLINICAL IMPLICATIONS: Educates providers as to which patients are more likely to choose ILX. STRENGTHS & LIMITATIONS: Our study has a large sample size and all patients received the same standardized treatment discussion. Our study is limited by the absence of insurance data on all patients, and its retrospective single center design. CONCLUSION: ILX was chosen by the minority of stable PD patients. While moderate to severe instability and significant bother is predictive of ILX use, other demographic factors including relationship status, sexual orientation or pain were not. Punjani N, Nascimento B, Salter C, et al. Predictors of Pursuing Intralesional Xiaflex in Peyronie's Disease Patients. J Sex Med 2021;18:1258-1264.

Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men.

BACKGROUND: It is currently unclear if men with Peyronie's Disease (PD) who achieve minimal benefits with the first 2 series of Collagenase Clostridium Histolyticum (CCH) injections should continue with additional injections. AIM: To analyze curvature improvements from the final two series of CCH injections based on amount of improvement during the first 2 series. METHODS: A prospective registry was analyzed of all men undergoing CCH injections for PD at a single institution. Men were included if they had completed a full 4 series (8 injections) of CCH and had baseline, interval (after 2 series), and/or final (after 4 series) curvature assessments available. Men were stratified into cohorts using baseline-to-interval assessments of ≤10° (or ≤20%) and >10° (or >20%), and improvements were compared using interval-to-final assessments. OUTCOMES: The primary outcome was interval-to-final curvature improvements stratified by ≤10°/>10° or ≤20%/>20% improvements achieved during the baseline-to-interval period. Secondary outcomes included analyses of demographic and pathophysiologic variables to determine associations with significant improvements during the final 2 CCH series. RESULTS: A total of 296 PD men were identified as receiving at least one CCH injection, of whom 175 had baseline-to-interval, 84 interval-to-final, and 115 with baseline-to-final measurements. Mean age was 56.6, PD duration 28.6 months, baseline curvature 63.4°, hourglass deformity 36.2%, and calcification 20%. Mean overall curve improvement was -21.5° (33.1%). Among men who experienced ≤20% improvements after 2 series, the mean subsequent curvature change was -24.6% during the final two series (vs +4.3% of those with >20% initial improvement, P< .001), and they were 2.7x more likely to experience >20% subsequent curve improvements. Thirty-one percent of those who achieved >10° during the first 2 series experienced benefits during the final 2 series compared to 70% of men who had ≤10° improvement initially. No demographic or pathophysiological variables predicted likelihood for improvements during the final 2 series of injections. CLINICAL IMPLICATIONS: Men who fail to achieve significant benefits with 2 series of CCH injections may benefit from completing the final 2 series. STRENGTHS AND LIMITATIONS: Strengths including a relatively large, prospective series. Limitations include a single center, nonrandomization, nonblinded assessments, and restriction to men who completed eight injections. CONCLUSIONS: In the current series, approximately 2/3 of men who fail to achieve >10° or 20% curve improvements with an initial 2 series of CCH injections achieved >10° or 20% improvements with the subsequent 2 series. Alom M, Burgon H, Ziegelmann M, et al. Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men. J Sex Med 2021;18:1092-1098.

Lateral herniation during treatment with collagenase Clostridium histolyticum (Xiaflex) for Peyronie's disease.

BACKGROUND: Collagenase Clostridium histolyticum (CCH), also know as Xiaflex, with penile modeling is considered to be the gold standard non-surgical option for management of Peyronie's disease and is known to be safe and efficacious. Corporal rupture is a rare but known adverse event of CCH treatment, however there are limited studies describing corporal herniation without rupture. Here we present a patient who experienced a rare complication following CCH injections for Peyronie's disease: lateral herniation of the tunica albuginea in the setting of a dorsal penile plaque. CASE PRESENTATION: A 58-year-old male presented to our clinic seeking treatment for Peyronie's disease. On exam, he was found to have a palpable dorsal plaque and > 30 degrees leftward curvature of the penis. He was deemed an appropriate candidate for and patient decided to proceed with CCH and modeling. He received 2 cycles of CCH injections (4 total CCH injections) with in-office and at-home penile modeling, per manufacturer's protocol. Two weeks following in-office modeling during his second CCH cycle, the patient reported a painless, soft swelling involving the left side of his penile shaft only occurring with erection. Exam and history were suggestive of lateral herniation rather than corporal rupture. CCH was discontinued. Patient declined further evaluation with penile ultrasound. CONCLUSIONS: This is the first case report detailing lateral herniation with CCH injections. Symptoms and exam that should raise suspicion of corporal herniation are a soft, painless mass with erection.

Peyronie's Disease Intervention Studies: An Exploration of Modern-Era Challenges in Study Design and Evaluating Treatment Outcomes.

INTRODUCTION: Peyronie's disease (PD) is characterized by pain, deformity, sexual dysfunction, and psychological bother. Several treatments are available with varying levels of efficacy, and significant limitations exist with the currently available literature. AIM: To explore modern-era methodological challenges inherent to PD research as they pertain to intervention studies. METHODS: We performed a critical review of the PD intervention literature to identify common methodological challenges with emphasis on aspects of patient assessment and treatment outcomes, study design, and statistical analysis. The key objective was to provide an impetus on which to build future research protocols, rather than focus on weaknesses with any individual studies. MAIN OUTCOME MEASURE: Expert opinion was used to summarize limitations with commonly reported objective outcomes such as penile curvature, girth, and length along with imaging modalities and objective questionnaires. Appropriate study design and statistical analysis were also reviewed to discuss common pitfalls in the PD literature. RESULTS: There are multiple shortcomings inherent to studying objective PD outcomes such as penile curvature, girth, and length. These include lack of standardized protocols for preintervention and postintervention assessment, interobserver and intraobserver variability, and lack of consistent definitions for what defines an objective outcome as clinically "meaningful" for patients. Similarly, imaging studies including penile ultrasound are subject to marked variation, thereby limiting their utility to measure predefined primary or secondary study outcomes including cavernosal artery hemodynamics and penile plaque size. Objective and validated questionnaires such as the Peyronie's Disease Questionnaire and International Index of Erectile Function require that patients have recently engaged in sexual activity, which is challenging for many patients as a result of penile deformity with PD. Finally, careful study design and statistical analysis (including appropriate study power) are imperative to ensure reliable results. Current shortcomings in the majority of studies contribute to the low level of evidence available for most PD interventions. CLINICAL IMPLICATIONS: Future PD intervention studies should focus on optimizing study design and statistical analysis. Furthermore, authors must incorporate standardized protocols for assessing preintervention and postintervention outcomes. STRENGTH & LIMITATIONS: The current analysis and recommendations for future study are based on the expertise and opinion of the manuscript authors. CONCLUSION: Multiple areas of weakness in study design, statistical analysis, and patient outcomes assessment limit the reliability of data derived from PD intervention studies in the modern era. The global themes identified herein should serve as a basis upon which to build future research protocols. Ziegelmann MJ, Trost LW, Russo GI, et al. Peyronie's Disease Intervention Studies: An Exploration of Modern-Era Challenges in Study Design and Evaluating Treatment Outcomes. J Sex Med 2020;17:364-377.

Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes.

BACKGROUND: A subset of patients with Peyronie's disease (PD) treated with collagenase clostridium histolyticum (CCH) experience persistent bother and some require surgery. AIM: We characterize patients experiencing persistent bother after CCH treatment and identify associations and predictors of surgical intervention/outcomes. METHODS: We retrospectively identified patients with PD from October 2014 to October 2019 and identified those presenting with persistent bother after CCH treatment by other urologists. Intracavernosal injection and penile Doppler ultrasonography were performed, and subsequent interventions/outcomes were recorded. Baseline characteristics were compared with Student t-test and chi-square test. Predictors of surgical intervention and complications were assessed using multivariable logistic regression. OUTCOMES: The primary outcome was surgery after CCH treatment. Secondary outcomes included worsened erectile function, sensory deficits, and penile length change. RESULTS: Of 573, 67 (11.7%) patients with PD had undergone prior CCH treatment with median 6 injections (range 2-24). Mean post-CCH PD Questionnaire bother score was 10.1 (SD: 3.1), and total International Index of Erectile Function-5 was 15.3 (SD: 8.7). Mean PD duration was 27.8 (SD: 35.7) months, with a mean composite curvature (MCC) of 69.0° (SD: 33.8) measured after injection. Of 67, 44 (65.7%) patients had MCC >60°. Of 67, 52 (77.6%) patients had indent, narrowing, or hourglass and 26 (38.8%) had hinge effect (buckling of the erect penis with axial pressure) on examination. Calcification was identified in 26 of 67 (38.8%) patients, with grade 3 calcifications comprising 6 of 23 (26.1%) patients. Of 67, 33 (49.3%) patients underwent surgery, with 20 (60.1%) undergoing partial plaque excision and grafting with/without tunica albuginea plication, 6 (18.2%) undergoing tunica albuginea plication alone, and 7 (21.2%) undergoing penile prosthesis with plaque incision and grafting. Surgical patients had greater mean curvature (82.6 vs 55.4, P = .001) and were more likely to have hinge (54.5% vs 20.6%, P = .005). On multivariable analysis, MCC ≥60° predicted patient's decision for surgery (odds ratio: 2.99, P < .01, 95% confidence interval: 1.62-4.35). There were no associations between surgical complications and number of injections or CCH-associated adverse events. CLINICAL IMPLICATIONS: Patients presenting with persistent bother after CCH treatment often have narrowing and calcifications (despite calcifications being a contraindication to CCH treatment), and those who have hinge or severe curvature are more likely to undergo surgery with low rates of complications. STRENGTHS/LIMITATIONS: This study's generalizability is limited by selection bias, but useful data are provided for patient counseling. CONCLUSION: Patients with persistent bother after CCH treatment had high rates of indentation/narrowing, plaque calcifications, and MCC >60° at completion of CCH treatment. Surgical intervention is more common with hinge and is safe and feasible in these patients, with low rates of complications. These findings suggest possible negative prognostic factors for CCH treatment, which merit further investigation. Bajic P, Wiggins AB, Ziegelmann MJ, et al. Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes. J Sex Med 2020;17:1005-1011.

Characteristics predictive of response to collagenase clostridium histolyticum for Peyronie's disease: a review of the literature.

PURPOSE: To evaluate characteristics predictive of successful treatment outcomes of Peyronie's disease (PD) with collagenase clostridium histolyticum (CCH) METHODS: CCH is the only FDA-approved medication for treating PD. We reviewed the literature that addresses pre-treatment clinical characteristics that may predict favorable response to CCH therapy. RESULTS: Despite significant heterogeneity in reporting treatment success, we identified four well-studied characteristics that may be predictive of favorable response to CCH therapy: baseline penile curvature, baseline IIEF, duration of PD, and presence of calcification. CCH demonstrated a favorable response in those with pre-treatment curvature 30°-60°, longer duration of disease, mild to moderate baseline sexual function, and low calcification within plaques. Of all factors, calcification is emerging as the most significant factor likely because CCH is unable to degrade the calcified plaques. There is difficulty interpreting results because of differences in reporting outcomes. Some studies compared treatment groups to placebo, others reported changes in curvature, while others reported > 20% curvature correction as treatment success. Additionally, not all studies reported outcomes after completion of four cycles of CCH, and recent studies utilized a shortened, high dose, modified protocol. CONCLUSIONS: The ideal candidate for CCH therapy remains elusive. Based on the available literature, the man with PD who will have the greatest chance of curvature improvement will have curvature between 30° and 60°, longer duration of disease, an IIEF > 17, no calcification, and set to receive all four cycles. For a greater understanding of CCH treatment success in PD, prospectively collected registry reporting standardized outcomes are needed.

Managing complications of collagenase Clostridium histolyticum (CCH) injection.

PURPOSE: The introduction of collagenase Clostridium histolyticum (CCH) has revolutionized the treatment of Peyronie's disease. The efficacy of this therapy has been well demonstrated and the safety profile is favorable. However, post-injection complications are poorly characterized and management of these complications lacks standardization. METHODS: This review includes literature published in English and indexed in the PubMed®, Embase® or Google Scholar™ databases. What follows is a synopsis of relevant articles, including original research studies, in an attempt to better define CCH complications and their respective management strategies. RESULTS: Adverse effects of therapy are common but generally self-limiting. Penile pain and edema are expected events, and most patients experience hematologic sequelae (bleeding, hematoma, ecchymosis, etc.). The intervention rate for penile hematoma is low. Penile fracture is a morbid complication of therapy that is rare and may be challenging to diagnose given the frequency with which pronounced bruising and swelling are encountered. Imaging is a useful adjunct in situations of diagnostic uncertainty. Alternative injection protocols have been evaluated to limit the cost and morbidity of CCH therapy. Clinical efficacy of these protocols is promising, but prospective evaluation is lacking. CONCLUSIONS: No standardized protocols exist for management of post-injection complications of CCH therapy. The majority of these complications are managed conservatively, but suspected penile fracture should be carefully evaluated and imaging employed when needed. Future prospective studies of alternative injection protocols are warranted to decrease morbidity while maintaining efficacy.

Peyronie's disease: Contemporary evaluation and management.

Peyronie's disease is a common yet poorly understood condition characterized by penile pain, curvature, sexual dysfunction and psychological bother. Peyronie's disease represents a penile wound healing disorder, and is thought to arise from exuberant scarring in response to penile trauma in genetically predisposed men. In the absence of active treatment, the majority of men experience stable or worsening symptoms, with few reporting spontaneous resolution in penile curvature or other deformity. In contrast, penile pain improves or resolves in the majority of men. Treatment options vary based on symptom severity and stability. Several oral therapies are commonly prescribed, although to date there are no strong data to support any oral agents as monotherapy for Peyronie's disease. Other options including penile traction therapy and intralesional injections result in modest improvements for many patients, particularly when used early after symptom onset. Penile straightening through approaches, such as penile plication and plaque incision or partial excision and grafting, represent the most rapid and reliable approach to correct penile curvature once the symptoms have stabilized. Side-effects vary based on the type of surgery carried out, and include penile shortening, sensation changes and erectile dysfunction in the minority of men. In patients with drug refractory erectile dysfunction and Peyronie's disease, placement of a penile prosthesis will address both issues, and is associated with high levels of patient satisfaction. The current review provides a practical approach to the modern evaluation and management of patients presenting with Peyronie's disease.

Optimizing collagenase Clostridium histolyticum therapy for Peyronie's disease using a novel approach with percutaneous needle tunnelling.

OBJECTIVES: To compare the efficacy and safety of a combined treatment of percutaneous needle tunnelling (PNT) and a modified collagenase Clostridium histolyticum (CCH) protocol (PNT/CCH) vs the modified protocol alone (CCH) in the treatment of Peyronie's disease (PD). PATIENTS AND METHODS: A prospective registry of patients treated with a modified CCH protocol was maintained between June 2014 and February 2018. The last 50 patients received PNT as an adjuvant therapy (PNT/CCH), and their data were compared with those of the other 94 patients treated previously (CCH). PNT involves the creation of multiple holes made percutaneously in the plaque before each injection. The modified protocol consisted of two collagenase injections, at 1-week intervals, followed by penile modelling. Patients used penile traction therapy, tadalafil and pentoxifylline for the next 2 months and were followed up for 6 months. The main outcome was improvement of curvature. Secondary outcomes were improvements in erectile function, PD symptoms, stretched penile length and satisfaction. RESULTS: Improvement in curvature was greater in patients in the PNT/CCH group than in the CCH group (mean ± sd 19.2 ± 6.1° vs 12.7 ± 5.0°; P < 0.001 [36.2 ± 12.5% vs 28.1 ± 14.5%; P = 0.001]). Compared with baseline, both interventions were associated with significant improvement in secondary outcomes. The main complications were ecchymosis, bruising and penile pain, with no significant differences between groups. CONCLUSIONS: Treatment of PD with CCH using our modified protocol in combination with PNT is safe and more effective than the modified protocol alone, with the potential for improved cost-effectiveness.

The Effects of Collagenase Clostridium histolyticum on Plantar Fibromatosis: A Case Study.

Plantar fibromatosis, also known as Ledderhose's disease, is a rare disorder of benign fibroblast proliferation involving the plantar aponeurosis (i.e., plantar fascia). Traditionally, surgical intervention has been the most common treatment for plantar fibromatosis. However, numerous studies have reported high recurrence rates of plantar fibromatosis after surgical intervention, as well as wound healing difficulties and nerve injury. Plantar fibromatosis often coexists with other superficial fibrous diseases such as Dupuytren's contracture and Peyronie's disease; immunohistochemical and ultrastructural analyses suggest a relationship between Ledderhose's disease and Dupuytren's contracture. The US Food and Drug Administration approved collagenase Clostridium histolyticum for the treatment of Dupuytren's contracture in 2010 and Peyronie's disease in 2013. This case study presents the successful treatment of Ledderhose's disease almost 4 years (45.5 months) after off-label use of collagenase C. histolyticum injection in a 22-year-old white female who had recurrent plantar fibromatosis after surgical intervention.

Sildenafil 25 mg ODT + Collagenase Clostridium hystoliticum vs Collagenase Clostridium hystoliticum Alone for the Management of Peyronie's Disease: A Matched-Pair Comparison Analysis.

INTRODUCTION: The effectiveness of phosphodiesterase type 5 (PDE5) inhibitors over the conservative management of Peyronie's disease (PD) has been widely questioned. AIM: To determine the role of sildenafil 25 mg film formulation twice a day (S25 b.i.d.) in the improvement of curvature after treatment of collagenase of Clostridium hystoliticum (CCH) in penile curvature owing to PD. METHODS: From April 2017 to April 2018, 161 consecutive patients were treated with S25 b.i.d. + CCH or CCH alone. Adjustment variables consisted of age, penile curvature, and the 15-question International Index of Erectile Function (IIEF-15) questionnaire at baseline using 1:1 propensity-score matching. Overall, 50 patients were considered subdivided into the following: 25 patients who received S25 b.i.d. + CCH (group A) and 25 who received CCH alone (group B). Patients received CCH injection using a shortened protocol and vacuum device in both groups. MAIN OUTCOME MEASURE: The primary outcome of the study was the change in penile curvature after treatment, and secondary outcomes were the change in sexual function (IIEF-15) and in the Peyronie's Disease Questionnaire (PDQ) and its subscores, PDQ-PS (psychosexual symptoms), PDQ-PP (penile pain), and PDQ-SB (symptom bother). RESULTS: Overall, mean penile curvature was 47.0° (SD 21.88), the mean IIEF-EF (erectile function) was 23.56 (SD 4.10), and the mean PDQ was 27.06 (SD 13.55). After the treatment, we observed a mean change for penile curvature of 25.6 (SD 9.05) in group A and -25.6 (SD 9.7) in group B (P < .01), for IIEF-EF of 2.28 (SD 2.33) in group A and 1.36 (SD 1.77) in group B (P = .03), for PDQ-PS of -3.04 (SD 2.95) in group A and of -2.12 (SD 2.06) in group B (P = .11), for PDQ-PP of -1.0 (SD 4.48) in group A and of -0.88 (SD 2.04) in group B (P = .60), for PDQ-SB of -5.84 (SD 4.58) in group A and of -4.16 (SD 4.45) in group B (P = .60), and for Female Sexual Function Index of 3.8 (SD 2.45) in group A and of 2.72 (SD 2.28) in group B (P = .14). We found a rate of global satisfaction of 70.83% in group A and of 84.0% in group B (P = .27). CLINICAL IMPLICATIONS: Addition of S25 b.i.d. to CCH is superior to CCH alone for improving penile curvature and erectile function. STRENGTH & LIMITATIONS: This is the first study comparing sildenafil + CCH vs CCH alone for the treatment of PD. Lack of randomization and direct verification of appropriate use of penile modeling could be considered limitations. CONCLUSION: In this study, combination therapy was superior in terms of penile curvature and erectile dysfunction improvement. Cocci A, Cito G, Urzì D, et al. Sildenafil 25 mg ODT + collagenase Clostridium hystoliticum vs collagenase Clostridium hystoliticum alone for the management of Peyronie's disease: A matched-pair comparison analysis. J Sex Med 2018;15:1472-1477.

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

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

BACKGROUND: To determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules. METHODS: In 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. RESULTS: In 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. CONCLUSION: In 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 REGISTRATION: ClinicalTrials.gov identifier: NCT02193828 . Date of trial registration: July 2, 2014 to December 5, 2014.

Results of SMSNA Survey Regarding Complications Following Intralesional Injection Therapy With Collagenase Clostridium Histolyticum for Peyronie's Disease.

INTRODUCTION: Intralesional injection of collagenase clostridium histolyticum (CCH) for Peyronie's disease (PD) can result in serious adverse events such as hematoma formation and corporal rupture. AIM: To investigate the prevalence of complications from CCH and management trends among CCH prescribers. METHODS: A survey was sent to all 693 members of the Sexual Medicine Society of North America (SMSNA) with valid email addresses. Responders were asked to participate if they were prescribers of CCH. Data regarding prescriber experience with CCH, procedural preferences, and rates and management strategies of complications were collected. MAIN OUTCOME MEASURE: One hundred SMSNA members completed the survey, with 36%, 23%, and 41% of responders having performed ≤10, 10 to 20, and >20 CCH injections, respectively. RESULTS: Of the responders, 94% reported hematomas in <25% of patients, with 63% preferring to observe and 37% treated with a combination of observation, application of a compressive dressing, and/or drainage of the hematoma. Corporal ruptures were encountered by 34% of physicians at a median of 5 days (0.5 to 30 days) from the last CCH injection. Rupture was located over the treated plaque in 84% of cases, and surgical intervention was the preferred management option by 67% of members. A distal circumcising degloving incision was used in 76% of cases, and 62% of responders reported the quality of tissue to be worse than would be expected with a non-CCH penile fracture. There were no significant differences in erectile function, ability to have intercourse, change in penile curvature, and patient satisfaction among patients who underwent surveillance vs surgery. One observed patient developed a penile abscess. CONCLUSION: A wide variation exists among SMSNA members' strategies to prevent and manage complications of CCH. One in 3 prescribers reported encountering a corporal rupture during CCH therapy, and it is currently undetermined if there is a benefit of surgery vs conservative management.

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.

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

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

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

BACKGROUND: Peyronie'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. OBJECTIVE: To assess curvature improvement in calcified PD plaques treated with CCh. DESIGN, SETTING, AND PARTICIPANTS: We 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. INTERVENTION: Intralesional 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 ANALYSIS: Change 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 LIMITATIONS: Sixty 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. CONCLUSIONS: Men with calcified PD plaques improve with CCh treatment and show similar improvements regardless of calcification type. PATIENT SUMMARY: In 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.

Peyronie's Disease: An Outcomes-Based Guide to Non-Surgical and Novel Treatment Modalities.

The clinical landscape of Peyronie's disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie's disease, it can be challenging to gain a thorough understanding of this body of literature. In this clinical management review, the workup and current theories on the pathophysiology of Peyronie's disease are reviewed, and the most recent outcomes data on the currently available non-surgical treatment modalities are presented. With an accurate understanding of the current landscape of Peyronie's disease treatment, sexual health providers will be able to better evaluate and engage in evidence-based shared decision-making with their patients.

Collagenase Treatment for Dupuytren Contracture of the Metacarpophalangeal Joint After Arthrodesis of the Proximal Interphalangeal Joint.

Successful collagenase (Xiaflex) treatment of Dupuytren's contracture in the metacarpophalangeal joint is possible in the presence of previous arthrodesis of the proximal interphalangeal joint.