Outcomes and Early Recurrence Following Enzymatic (Collagenase) Treatment of Moderate and Severe Dupuytren Contractures.

PURPOSE: We offer collagenase Clostridium histolyticum (CCH) injections to all patients with a Dupuytren contracture and a palpable cord. We assessed whether more severe contractures respond less well or recur more frequently. METHODS: From a database of 502 CCH injections, 386 (77%) had a complete dataset with minimum 1-year face-to-face follow-up. Contracture severity was assessed using the Tubiana system: grade 1 (27%), grade 2 (49%), grade 3 (19%), and grade 4 (5%). Patients received a single intralesional injection of 0.58 mg CCH followed by manipulation. Finger position was measured at 6 to 12 weeks, 6 months, and 1 year. Failure to break the cord, skin tears, and any adverse events were noted. Recurrence was defined as a failure to maintain any prior correction to within 20°. RESULTS: There were 17 failures (4%) and 6 allergic reactions (1%). We found 31% corrected completely, with approximately half remaining corrected at 1 year. We achieved 43° (95% confidence interval, 40°-46°) correction of combined deformity, with 11° (95% confidence interval, 9°-13°) correction attrition over 1 year. Sixteen percent of treated digits experienced a recurrence with no difference between Tubiana grades, and one-third chose further treatment. Following treatment, Tubiana grade 1 contractures improved by 78% in comparison with higher grade contractures (55%-67% relative correction). By 1 year, all grades had a similar mean 46% relative correction. A complete correction was seen in 61% of grade 1 contractures, with more severe contractures less likely to correct completely (9%-24%). A 31% skin tear rate had no impact on outcome, recurrence, or long-term morbidity. CONCLUSIONS: CCH may treat any Dupuytren cord regardless of severity. Although contracture may recur, few patients pursue further treatment within 1 year. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

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.

Prospective observation of Clostridium histolyticum collagenase for the treatment of Dupuytren's disease in 788 patients: the Austrian register.

INTRODUCTION: Since March 2011, the microbial collagenase of Clostridium histolyticum (Xiapex®, Swedish Orphan Biovitrum AB, Stockholm, Sweden) has become available in the European Union for treatment of Dupuytren's disease. The purpose of this study was to evaluate potential safety risks of Xiapex® and to contribute to a better understanding for its use. METHODS: A prospective, non-interventional, observational study using Xiapex® for Dupuytren's disease named XIANIS was conducted between 1.10.2011 and 01.10.2017. Treatment was conducted in accordance to the manufacturer information. Patients were invited for follow-up after 1 week, 1 month, 3 months and 1 year. Demographic data, treatment data, pain levels, anaesthetic application during passive manipulation, subjective function improvement, subjective satisfaction and adverse events were recorded. RESULTS: 788 patients with 814 treatments were included who suffered from Dupuytren's contracture for a mean of 64 months. The metacarpophalangeal joint was affected in 57% of cases and the PIP joint in 40.8% with a mean contracture of 39° and 56°, respectively. A change in the contracture down to 0°-5° was reported in 66.5% of cases, while 25.5% achieved a partial improvement. The pain during the injection was rated 4.5 and 3.3 during passive manipulation. Adverse events were reported in the majority of treated patients with skin tears being one main common event (26%). Further adverse outcomes were bleeding/hematoma, joint swelling, injection-site swelling, pressure sensitivity, erythema, injection-site pain, peripheral edema, blood blisters, blisters, painless lymphadenopathy, painful lymphadenopathy, axillary pain, arthralgia and sensory abnormality. There were no reported tendon ruptures, anaphylactic reactions or ligament injuries. On 1-year follow-up, 29% showed an increased contracture of a mean of 24° with the need for surgical treatment in 2% of patients. 74% of patients were very satisfied and 72% showed a high functional improvement. CONCLUSION: The injectable collagenase Clostridium histolyticum (Xiapex®) proved to be effective and safe in patients with Dupuytren's disease. Minor adverse events disappeared within 30 days and the need for surgical treatment within 1 year was very low (2%). No major complications or rare side effects were seen in this prospective observational study.

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.

Range of motion, postoperative rehabilitation and patient satisfaction in MCP and PIP joints affected by Dupuytren Tubiana stage 1-3: collagenase enzymatic fasciotomy or limited fasciectomy? A clinical study in 52 patients.

INTRODUCTION: In Switzerland, collagenase Clostridium histolyticum therapy (CCH) for Dupuytren's disease was introduced in 2011. This study analyzes possible differences between CCH and limited fasciectomy (LF) in terms of range of motion, patient satisfaction and postoperative rehabilitation. MATERIALS AND METHODS: This retrospective study included 52 patients with Dupuytren's disease stage 1-3 according to Tubiana, treated with CCH or LF between January 2012 and December 2013. Complications were analyzed for each patient. The contracture of each treated joint measured on average at the 3 months and up to 2 years follow-up was compared with the preoperative values. The Michigan Hand score was evaluated at 2 years and the patients were asked to subjectively evaluate the outcome of the treatment and whether they would repeat it if necessary. Postoperative rehabilitation was also precisely quantified. RESULTS: 11 minor complications were reported for a complication rate of 29% in the CCH group. No major complications were reported in both groups. In the CCH group, mean MCP joint contracture was, respectively, 44° ± 20°, 9° ± 2° (gain of mobility compared to the preoperative situation 35°, P < 0.001), and 10° ± 3° (gain 34°, P < 0.001), respectively, before, at the 3 months' control and at the 2-year clinical control. In the LF group, mean MCP joint contracture was, respectively, 30° ± 21°, 2° ± 0.5° (gain 28°, P < 0.001), and 1° ± 0.5° (gain 29°, P < 0.001) for the same control periods. In the CCH group, mean PIP joint contracture was, respectively, 51° ± 21°, 18° ± 3° (gain of mobility compared to the preoperative situation 33°, P < 0.001), and 32° ± 4° (gain 19°, P < 0.001), respectively, before, at the 3 months' control and at the 2-year clinical control. In the LF group, mean PIP joint contracture was, respectively, 30° ± 20°, 2° ± 0.5° (gain of mobility compared to the preoperative situation 28°, P < 0.001), and 11° ± 4° (gain 19°, P < 0.001) for the same control periods. Outcomes were compared across the LF and CCH groups: surgery performed better than collagenase for PIP joint treatment at early (P < 0.001) and 2-year follow-up (P = 0.004) controls. However, patient satisfaction was higher in the CCH group: 92% were satisfied or very satisfied of the treatment compared to 71% in the LF group. All patients would reiterate the treatment in the CCH group if necessary compared to only 71% in the LF group. Rehabilitation was highly reduced in the CCH group compared to the LF group. CONCLUSION: In this study, surgery performed better than collagenase at early and 2-year follow-up in PIP joints and similar in MCP joints. While surgery seems to achieve better results, collagenase is considered in Switzerland as an off-the-shelf therapy that provides consistent results without scars, with shorter rehabilitation time, minor hand therapy, shorter splinting time, and applicability. LEVEL OF EVIDENCE AND STUDY TYPE: Level III.

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.

Long-term assessment of collagenase treatment for Dupuytren's contracture: A 10-year follow-up study.

BACKGROUND: Enzymatic fasciotomy with collagenase clostridium histolyticum (CCH) has revolutionized the treatment for Dupuytren's contracture (DC). Despite its benefits, the long-term outcomes remain unclear. This study presented a comprehensive 10-year follow-up assessment of the enduring effects of CCH on patients with DC. AIM: To compare the short-term (12 wk) and long-term (10 years) outcomes on CCH treatment in patients with DC. METHODS: A cohort of 45 patients was treated with CCH at the metacarpophalangeal (MCP) joint and the proximal interphalangeal (PIP) joint and underwent systematic re-evaluation. The study adhered to multicenter trial protocols, and assessments were conducted at 12 wk, 7 years, and 10 years post-surgery. RESULTS: Thirty-seven patients completed the 10-year follow-up. At 10 years, patients treated at the PIP joint exhibited a 100% recurrence. However, patients treated at the MCP joint only showed a 50% recurrence. Patient satisfaction varied, with a lower satisfaction reported in PIP joint cases. Recurrence exceeding 20 degrees on the total passive extension deficit was observed, indicating a challenge for sustained efficacy. Significant differences were noted between outcomes at the 7-year and 10-year intervals. CONCLUSION: CCH demonstrated sustained efficacy when applied to the MCP joint. However, caution is warranted for CCH treatment at the PIP joint due to a high level of recurrence and low patient satisfaction. Re-intervention is needed within a decade of treatment.

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

Objective: 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 and methods: 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).The primary outcome was reduction in curvature and the ability to have penetrating sex again. Secondary outcomes include pain scores during injections, changes in PDQ-NL, PROM and complications of CCH treatment. Results: Sixty-three patients were included, mean age was 56.0 years (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. Conclusions: 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.

Safety and Efficacy Study of Collagenase Clostridium Histolyticum Applied With an Intensive Protocol in the Treatment of Peyronie's Disease.

INTRODUCTION: Collagenase clostridium histolyticum (CCH) is a treatment for Peyronie's disease (PD) whose efficacy and safety has been demonstrated using a classic protocol and a shortened protocol. AIM: To evaluate the efficacy and safety of an even more intense protocol in which a CCH injection is applied for 3 separate cycles of 1 week. METHODS: Prospective, nonrandomized, clinical study of a cohort of 13 patients with PD and non-ventral curvatures, between 30 and 90 degrees and with stable disease were included. Under local anesthesia, 0.9 mg of CCH is infiltrated in 3 parallel and equidistant transverse bands across the plaque in 3 sessions separated by 1 week. Between sessions the patient is instructed to perform home modeling and penis stretching. MAIN OUTCOME MEASURES: The measurements collected were from girth, length of the penis and length of the plaque. Side and degree of curvature. Ultrasound evaluation of the plaque characteristics and assessing the interface between the tunica albuginea and Buck's fascia. Furthermore, questionnaires were collected: International Index of Erectile Function (IIEF) and 15-question and Peyronie's Disease Questionnaire (PDQ). All these parameters were evaluated before and after treatment. RESULTS: An improvement in curvature was obtained in 76.9% of patients, reaching an improvement in the angle of curvature after the treatment cycles by an average of 19 ° (range 0-35 °) from the beginning. There are also improvements in the results of the IIEF and PDQ questionnaires. Length, penis girth, and plate length measurements hardly changed after treatment. Reported adverse effects are mild and limited to the penis. CONCLUSIONS: We demonstrate the safety and efficacy of CCH in the treatment of PD using a more intense protocol than the previous ones. In addition, reducing the overall duration of allows for greater adherence and compliance of patients. Melgarejo-Segura MT, Funes-Padilla C, Morales-Martínez A, et al. Safety and Efficacy Study of Collagenase Clostridium Histolyticum Applied With an Intensive Protocol in the Treatment of Peyronie's Disease. Sex Med 2021;9:100375.

Efficacy and safety of collagenase Clostridium histolyticum in Peyronie's disease following a modified treatment protocol. / Eficacia y seguridad de la colagenasa de Clostridium histolyticum en la enfermedad de Peyronie según un protocolo de tratamiento modificado.

INTRODUCTION: Collagenase 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 METHODS: We included patients with PD in stable phase, with curvatures of 30-90degrees. 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-degree curve was decreased, was reevaluated every 4weeks. 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. RESULTS: Thirty-one patients were treated under the modified protocol. The mean initial curvature was of 49.84 (±15.83) degrees. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42) degrees and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25) degrees. Most patients required one (19.4%) or two (54.8%) injections. No patient presented TRAEs. CONCLUSIONS: The 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.

At what cost is collagenase clostridium histolyticum viable for treating Peyronie's disease in a public healthcare system?

BACKGROUND: Collagenase clostridium histolyticum is a recognized non-surgical management for Peyronie's disease, licenced for use in the UK for patients with a palpable plaque and a curvature deformity of at least 30°. However, it is not currently funded for use within the National Health Service. Collagenase clostridium histolyticum has also recently been withdrawn from the European and other markets worldwide, but there is potential for this to be produced off-patent in the future. OBJECTIVES: To determine whether collagenase clostridium histolyticum is cost-neutral when compared to surgical management within a public health care system, using the National Health Service as an example. MATERIALS AND METHODS: Two published protocols for the administration of collagenase in Peyronie's disease were identified-the 'IMPRESS protocol' and the 'London protocol'. Costs were taken from published NHS literature. Surgical intervention rates after collagenase clostridium histolyticum administration and primary penile plication were taken from published literature. The costs of the two published protocols were calculated with costs of any repeat surgical intervention were included within each protocol per patient cost. RESULTS: At the current cost per vial of collagenase to the National Health Service, the IMPRESS protocol per patient costs £3,832.77 (143.7%) more than primary surgery, whilst the London protocol costs £70.77 (2.7%) more than primary surgery. DISCUSSION: At a cost of £548.41 per vial, collagenase administered under the London protocol would be a management option for Peyronie's disease cost neutral to primary corrective surgery. CONCLUSION: Central funding of collagenase in a public healthcare system would enable the management of Peyronie's disease to be moved to the outpatient setting. For this to be done at no additional cost to the NHS, it would require a cost reduction per vial of collagenase of £23.59 (4.1%), to a cost of £548.41.

DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytren's contracture.

INTRODUCTION: Dupuytren's contracture (DC) is a chronic fibroproliferative disorder of the palmar fascia which leads to flexion contracture in one or more fingers. There is no definitive cure for DC, and treatment aims at relieving symptoms by releasing the contracture using percutaneous or operative techniques. METHODS AND ANALYSIS: We planned a prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of (1) collagenase clostridium histolyticum injection followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and (3) primary limited fasciectomy during short-term and long-term follow-up for Tubiana I-III stages DC. We will recruit participants from seven national centres in Finland. Primary outcome is the rate of success in the treatment arm at 5 years after recruitment. Success is a composite outcome comprising (1) at least 50% contracture release from the date of recruitment and (2) participants in a patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of contracture, (2) quick disabilities of the arm, a shoulder and hand outcome measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major adverse events, (6) patient's trust of the treatment, (7) global rating, (8) rate of PASS, (9) rate of minimal clinically important improvement, (10) expenses, (11) progression of disease, (12) progression-free survival, (13) favoured treatment modality, (14) patients achieving full contracture release and >50% improvement and (15) patient satisfaction with the treatment effect. Predictive factors for achieving the PASS will also be analysed. ETHICS AND DISSEMINATION: The protocol was approved by the Tampere University Hospital Institutional Review Board and Finnish Medicine Agency. The study will be performed according to the principles of good clinical practice. The results of the trial will be disseminated as published articles in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03192020; Pre-results.

Collagenase clostridium histolyticum for the treatment of Peyronie's disease: a prospective Italian multicentric study.

Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4-weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0-40)° or 42.9 (0-67)% from baseline (p < 0.001). There was also a statistically significant improvement in all IIEF and PDQ questionnaires subdomains (p < 0.001 in all subdomains). This prospective multicentric study confirms that the three-injection protocol is effective enough to achieve a good result and to minimize the cost of the treatment.

Collagenase Clostridium histolyticum in the Treatment of Peyronie's Disease-A Review of the Literature and a New Modified Protocol.

INTRODUCTION: Peyronie's disease (PD) is a common condition that results in penile deformity, which makes sexual intercourse difficult or impossible, and causes psychological, emotional, and relationship difficulties for the man affected and his partner. Collagenase Clostridium histolyticum (CCH; Xiapex, Xiaflex) is the first licensed non-surgical treatment option for PD. The safety and efficacy have been demonstrated in two large phase III randomized controlled trials (IMPRESS I and IMPRESS II). AIM: To review the safety and efficacy of CCH and to introduce a new shortened modified protocol for CCH that was developed by the authors to decrease the cost and duration of treatment. METHODS: A review of the medical literature on CCH for inclusion in this review was obtained by searching the PubMed (from 1946) and Medline (from 1946) medical databases and from the screening of relevant bibliographies. The search terms Xiapex, Xiaflex, collagenase Clostridial histolyticum, and Peyronie's disease were used. Clinical trials in men with PD and scientific articles relating to pharmacologic data were included in the review. When possible, large, randomized, and well-designed trials were selected. MAIN OUTCOME MEASURES: Changes in the angle of penile curvature and in the Peyronie's Disease Questionnaire domains. RESULTS: The clinical trials demonstrate the safety and efficacy of CCH in the treatment of PD. The new modified protocol developed by the authors is as safe and effective as the protocol used in the clinical trials. CONCLUSION: CCH is the first licensed non-surgical treatment for PD. Its safety and efficacy have been demonstrated in large well-designed clinical trials. The new shortened modified protocol decreases the cost and duration of the treatment without compromising the safety and efficacy of the drug. This alteration will allow more patients to benefit from CCH. Abdel Raheem A, Johnson M, Abdel-Raheem T, et al. Collagenase Clostridium histolyticum in the Treatment of Peyronie's Disease-A Review of the Literature and a New Modified Protocol. Sex Med Rev 2017;5:529-535.

Collagenase Clostridium histolyticum: emerging practice patterns and treatment advances.

OBJECTIVE: This study aims to provide a comprehensive review of the role of Collagenase Clostridium histolyticum (CCH). METHODS: This review is based on a literature review and practical experience. RESULTS: This review provides practical management strategies for using collagenase by sharing clinical experiences over the past few years; logistical aspects of in-clinic treatment, lessons learned, and novel approaches to correct traditionally hard-to-treat contractures are discussed. In addition a brief, yet comprehensive overview is provided on the pathophysiology of the disease, the mechanism of collagenase action and results of clinical studies. CONCLUSION: CCH has an evolving role as one of the tools available for treating Dupuytren's disease.

[Collagenase injection in Dupuytren's disease, evaluation of the ultrasound assisted technique]. / Traitement de la maladie de Dupuytren par collagénase injectable, évaluation de l'échographie assistée.

Since October 2011, the enzymatic lysis of Dupuytren's cord was introduced in Switzerland (Xiapex(®), Auxilium Pharmaceuticals, Pfizer). Here we present our first university experience and underline the major role of ultrasound during the injection. Between December 2011 and February 2013, 52 injections were performed to eliminate 43 Dupuytren's cords in 33 patients. The mean age of the patients was 64.4 ± 8.5 years. Complications were documented for each patient. Before, directly after and after a minimum of 6 months post-injection, the contracture of the treated joint was measured with use of a goniometer. The DASH score was evaluated after a minimum of 6 months and the patients were asked to subjectively evaluate the outcome of the treatment (very good, good, mild, poor) and whether they would reiterate it if necessary. Four skin defects, one lymphangitis, and one CRPS were responsible for a complication rate of 18%. There was no infection and no tendon rupture in the series. The mean MCP joint contracture was respectively 36.8 ± 27.4°, 3.5 ± 7.8° (gain of mobility compared to the preoperative situation 33.3°, P<0.001), and 8.4 ± 13.9° (gain 28.4°, P<0.001) respectively before, just after and at the long-term clinical control. The mean PIP joint contracture was respectively 36.5 ± 29.1°, 5.9 ± 6.7° (gain 30.6°, P<0.001), and 15.1 ± 13.8° (gain 21.4°, P<0.001) respectively before injection, just after and at the long-term clinical control. The DASH score decreased from 24 ± 14 to 7 ± 9 (P<0.001). Eighty-one per cent of the patients were satisfied or very satisfied of the treatment. All but two would reiterate the treatment if necessary. Ultrasound is able to target the injection of collagenase in order to reduce complications. The short-term results of this non-invasive therapy are very promising however comparison with conventional procedures is difficult as the long-term results are lacking.

What is the better treatment for single digit dupuytren's contracture: surgical release or collagenase clostridium histolyticum (Xiapex) injection?

UNLABELLED: The purpose of this study was to compare the initial and final outcome range of motion in the MCP-J and PIP-J of single digit Dupuytren's Contracture treated with either open surgical excision or manipulation after collagenase clostridium histolyticum (CCH; Xiapex) injection. MATERIAL: Ten patients in either group. The range of motion measurements were statistically compared using the student t-test with a p-value of 0.05. There was no statistical difference in the pre-treatment status of the total active range of movement (TAM) between the two groups. RESULTS: Open surgical release achieved a statistically better initial outcome in combined total passive range of movement than the xiapex group (p = 0.0047), but at the final outcome the better TAM measurement at the MCP-J after surgery was not statistically significant. However, the total active range of movement was statistically better at the PIP-J level in the xiapex group (p = 0.01) and the MCP-J and PIP-J combined total active range of movement was statistically better in the xiapex group (p = 0.0258). CONCLUSION: Surgery achieved better initial outcome at both MCP-J and PIP-J levels, and at discharge, only extension in the MCP-J level was statistically better after open excision. However the final outcome was statistically better at the PIP-J level in extension (p = 0.006) and total active movement (TAM) (p = 0.008) after treatment with collagenase clostridium histolyticum. Further studies are required to assess the long-term differences between the two groups and to investigate the outcomes for patients with multi-digit involvement.

Eficacia y seguridad de la colagenasa de Clostridium histolyticum en la enfermedad de Peyronie según un protocolo de tratamiento modificado / Efficacy and safety of collagenase Clostridium histolyticum in Peyronie's disease following a modified treatment protocol

Introducción: La colagenasa de Clostridium histolyticum (CCH) es el único medicamento con licencia para el tratamiento conservador en la enfermedad de Peyronie (EP) que ha demostrado eficacia y seguridad en ensayos clínicos. Sin embargo, el protocolo de tratamiento estándar consume tiempo y recursos, por lo que presentamos un nuevo protocolo de tratamiento con CCH con un perfil más rentable. Nuestro objetivo es evaluar su eficacia y su seguridad.Materiales y métodosSe incluyeron pacientes con EP en fase estable, con curvaturas de 30-90°. Se excluyeron curvas ventrales y deformidades complejas. El protocolo de tratamiento consiste en una dosis completa de CCH inyectada a lo largo de la placa de EP formando 2 líneas de 4 inyecciones. Se educó a los pacientes en los ejercicios diarios de modelado del pene. La necesidad de un nuevo ciclo de tratamiento fue reevaluada cada 4semanas hasta un máximo de 8 ciclos o hasta la disminución de la curva de 30°. Para evaluar la eficacia se registraron los cambios en la curvatura y el número de ciclos. Para evaluar la seguridad se registraron los eventos adversos graves relacionados con el tratamiento, incluyendo la rotura de cuerpos cavernosos, hematoma peneano, hematuria e infección local.ResultadosUn total de 31 pacientes fueron tratados bajo el protocolo modificado. La curvatura inicial media fue de 49,84 (±15,83) grados. Se registró mejora en la curvatura en 25 pacientes (80,6%), con una disminución media absoluta de 20,65 (±15,42) grados y relativa del 44%. La curvatura media posterior al tratamiento fue de 30,67 (±17,25) grados. La mayoría de los pacientes requirieron una (19,4%) o dos (54,8%) inyecciones. Ningún paciente presentó eventos adversos graves relacionados con el tratamiento.ConclusionesLos resultados sugieren que el protocolo de tratamiento modificado con CCH es eficaz y seguro, pero se deben realizar más estudios que ayuden a optimizar el protocolo estándar actual. (AU)

Introduction: Collagenase 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 30-90degrees. 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-degree curve was decreased, was reevaluated every 4weeks. 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) degrees. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42) degrees and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25) degrees. 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. (AU)