Martin K. Gelbard

The natural history of peyronie's disease

The natural history of Peyronies disease was evaluated in 97 men by means of a questionnaire. Disease duration ranged from 3 months to 8 years. Questions addressed pain, bending, ability for intercourse, over-all effect of the disease, psychological effects, treatments received and degree of disease progression. Approximately 40% of the patients found pain, bending, ability for intercourse and over-all effects to be unchanged during the course of the disease. Bending and ability for relations worsened in 40% of the patients during the same interval, while only 6% had worsening of pain. Of the patients 77% reported psychological effects due to Peyronies disease, which improved in 28%, did not change in 36% and worsened in 36%. Over-all, 13% of the patients believed the disease to be one of gradual resolution, 47% believed there had been little or no change and 40% believed that the disease pattern was one of gradual progression. We found no statistically significant association between disease duration and spontaneous improvement in penile bending. A similar lack of statistical significance was found when improvement in a variety of categories was compared in patients who received no therapy versus those who received a variety of conventional medical therapies.

Collagenase Versus Placebo in the Treatment of Peyronie’s Disease: A Double-blind Study

We investigated 49 men with Peyronies disease in a prospectively randomized placebo controlled double-blind study, comparing the effects on plaque size and penile deformity of intralesional purified clostridial collagenase and saline placebo. For the group as a whole, treatment out-performed placebo (p < 0.007). When patients were analyzed with respect to disease severity, those with lesser deformity responded more favorably to treatment. The absolute angular change in patients responding to treatment was small. No significant side effects were noted within a 3-month followup.

Clinical Efficacy, Safety and Tolerability of Collagenase Clostridium Histolyticum for the Treatment of Peyronie Disease in 2 Large Double-Blind, Randomized, Placebo Controlled Phase 3 Studies

PURPOSE IMPRESS (Investigation for Maximal Peyronies Reduction Efficacy and Safety Studies) I and II examined the clinical efficacy and safety of collagenase Clostridium histolyticum intralesional injections in subjects with Peyronie disease. Co-primary outcomes in these identical phase 3 randomized, double-blind, placebo controlled studies included the percent change in the penile curvature abnormality and the change in the Peyronie disease questionnaire symptom bother score from baseline to 52 weeks. MATERIALS AND METHODS IMPRESS I and II examined collagenase C. histolyticum 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 collagenase C. histolyticum, that is 2 injections per cycle separated by approximately 24 to 72 hours with the second injection of each followed 24 to 72 hours later by penile plaque modeling. Men were stratified by baseline penile curvature (30 to 60 vs 61 to 90 degrees) and randomized to collagenase C. histolyticum or placebo 2:1 in favor of the former. RESULTS Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with collagenase C. histolyticum 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 Peyronie disease 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. CONCLUSIONS IMPRESS I and II support the clinical efficacy and safety of collagenase C. histolyticum for the physical and psychological aspects of Peyronie disease.

Expanding contractures of the tunica albuginea due to Peyronie's disease with temporalis fascia free grafts.

We describe a procedure to expand contractures of the tunica albuginea by multiple full thickness relaxing incisions followed by inlay of tailored temporalis fascia free grafts. This technique is performed without resection of the tunica albuginea, although in the case of calcified plaques the calcifications themselves are removed, preserving the overlying tunica. Between September 1988 and February 1990, 12 patients have undergone this procedure, all of whom have greater than 3 months of followup and have experienced spontaneous erections within the first week postoperatively. Of the patients 11 resumed intercourse within 8 weeks of surgery and 1 required 12 weeks. No patient had sensory loss postoperatively and there has been no donor site morbidity. Correction of curvature was accomplished in all patients and there have been no recurrences within a maximal followup of 22 months. Within the limitations of such a small study we believe that there is evidence supporting this approach in potent patients with severe acquired penile curvature.

The use of collagenase in the treatment of Peyronie's disease

Purified clostridial collagenase was administered intralesionally in 31 men with Peyronies disease. Within 4 weeks of treatment 20 patients showed an objective improvement. Pain was eliminated in 13 of 14 patients with this complaint at presentation within the same 4-week period. The ability to have intercourse was restored in 3 of 4 patients with this problem. Except for a small corporeal rupture at the site of injection in 1 patient, no significant untoward effects were noted. During the mean 9.8-month followup 1 recurrence of bending was noted.

Collagenase for Peyronie's disease experimental studies.

SummaryThis pilot study was designed to test the feasibility of using purified clostridial collagenase in the clinical management of Peyronies disease. The basic properties of this agent are discussed. We studied its effect on Peyronies plaque tissue by a quantitative in vitro assay utilising the liberation of free α-amino groups as an index of enzymatic collagenolysis. Tissue from three patients with Peyronies disease was used. Tunica albuginea from a second group of three normal patients was studied in the same manner, and no selectivity for the collagen of Peyronies plaques was identified. Utilising human pericardium as a uniform collagenous substrate, a simple dose-effect relationship was established, and the distribution characteristics of injected collagenase observed. Its effects on blood vessels and nerves in vivo was determined as well as the effects of collagenase on the histology of normal and diseased human tissue in vitro. A tentative dose for use in Peyronies disease was established, which is discussed in light of existing toxicological data. The study was designed to test the eeasibility of purified collagenase in the clinical management of Peyronies disease. Data included detail plaque digestion and dose-effect relationships in vitro, as well as the histological effects on plaques, blood vessels, and nerves in vivo and in vitro. It is concluded that collagenase may warrant further clinical testing in the treatment of Peyronies disease.

Phase 2b Study of the Clinical Efficacy and Safety of Collagenase Clostridium Histolyticum in Patients With Peyronie Disease

PURPOSE Collagenase Clostridium histolyticum is an investigational nonsurgical treatment for Peyronie disease. In this phase 2b, double-blind, randomized, placebo controlled study we determined the safety and efficacy of collagenase C. histolyticum and assessed a patient reported outcome questionnaire. MATERIALS AND METHODS A total of 147 subjects were randomized into 4 groups to receive collagenase C. histolyticum or placebo (3:1) with or without penile plaque modeling (1:1). Per treatment cycle 2 injections of collagenase C. histolyticum (0.58 mg) were given 24 to 72 hours apart. Subjects received up to 3 cycles at 6-week intervals. When designated, investigator modeling was done 24 to 72 hours after the second injection of each cycle. We evaluated penile curvature by goniometer measurement, patient reported outcomes and adverse event profiles. RESULTS After collagenase C. histolyticum treatment significant improvements in penile curvature (29.7% vs 11.0%, p=0.001) and patient reported outcome symptom bother scores (p=0.05) were observed compared to placebo. In modeled subjects 32.4% improvement in penile curvature was observed in those on collagenase C. histolyticum compared to 2.5% worsening of curvature in those on placebo (p<0.001). Those treated with collagenase C. histolyticum who underwent modeling also showed improved Peyronie disease symptom bother scores (p=0.004). In subjects without modeling there were minimal differences between the active and placebo cohorts. Most adverse events in the collagenase C. histolyticum group occurred at the injection site and were mild or moderate in severity. No treatment related serious adverse events were reported. CONCLUSIONS Collagenase C. histolyticum treatment was well tolerated. We noted significant improvement in penile curvature and patient reported outcome symptom bother scores, suggesting that this may be a safe, nonsurgical alternative for Peyronie disease.

Relaxing Incisions in Correction of Penile Deformity Due to Peyronie's Disease

PURPOSE The use of tunica albuginea relaxing incisions, a common component of several operative techniques for correction of penile deformity due to Peyronies disease, is reviewed. MATERIALS AND METHODS Of 93 operations performed for penile straightening 24 involved relaxing incisions with penile prosthesis implantation but no grafts and 69 involved autologous free grafts into relaxing incisions without use of an implant. RESULTS Relaxing incisions were uniformly effective in correcting penile curvature when used in conjunction with a prosthesis. When autologous grafts were used without an implant, more than 80% of the patients with dorsal or ventral bending had a good result, compared to only 17% with lateral bending. CONCLUSIONS Relaxing incisions are an effective technique for changing the shape of the erect penis by altering the configuration of the tunica albuginea at maximal extension.

Clinical Safety and Effectiveness of Collagenase Clostridium Histolyticum Injection in Patients with Peyronie's Disease: A Phase 3 Open‐Label Study

INTRODUCTION Collagenase clostridium histolyticum (CCH; Xiaflex, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration-approved, intralesional treatment for Peyronies disease (PD). AIM The aim of this study was to assess the safety and effectiveness of CCH in the treatment of PD. METHODS This phase 3, open-label study enrolled subjects who were CCH-naïve, were enrolled in a previous pharmacokinetic study, or had received placebo in an earlier phase 2 CCH study. Each treatment cycle included two intralesional injections of CCH 0.58 mg, approximately 24-72 hours apart, and plaque modeling 24-72 hours after the second injection of each cycle. The treatment cycle was repeated after 6 weeks for ≤4 treatment cycles. MAIN OUTCOME MEASURES The co-primary end points were the mean percent change in penile curvature deformity and the mean improvement in PD bother score (range 0-16) from baseline to week 36. RESULTS Of the 347 subjects treated with ≥1 injection, 238 had both a penile curvature measurement and a Peyronies Disease Questionnaire response at baseline and ≥1 subsequent time point. Mean baseline penile curvature deformity was 53.0° and mean PD symptom bother was 7.3. Statistically significant mean improvements from baseline to week 36 were observed in both penile curvature deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or moderate in severity and local to the penis. There were three serious treatment-related AEs, two penile hematomas and one corporal rupture; all resolved with treatment. CONCLUSIONS Potentially clinically meaningful and statistically significant improvements in penile curvature deformity and PD symptom bother scores were observed with intralesional injection of CCH compared with baseline in men with PD. CCH was generally well tolerated, with AEs primarily transient and local to injection site. In conjunction with previous studies, the results of this open-label study support the use of CCH in the treatment of PD.

A Technique for Immediate Realignment and Catheterization of the Disrupted Prostatomembranous Urethra

A technique is described that has successfully permitted prompt atraumatic urethral realignment and stenting after prostatomembranous urethral disruption in 7 patients.