ESSM Newsletter # 39

12 ESSM Today Can collagenase make it right? by Borja García Gómez and Javier Romero Otero About Peyronie’s disease Peyronie´s disease (PD) is condition that results from fibrotic plaque formation of the tunica al- buginea, and it can result in a number of pe- nile deformities such as cuvature, shortening, narrowing, hour-glass deformity and/or hinge deffect. PD usually affects men in their 50s and the estimated incidence varies from 3% to 9% [1]. The etilogy of PD remains unknown, but the most accepted hyphotesis is that vascular mi- crotrauma during sexual intercourse releases an uncontrolled inflammatory reaction in genetically susceptible men (2). The most common presentation of PD is in two well divided phases: acute and chronic. During the acute inflammatory phase the plaque begins to form and the deformities become apparent. Men tipically present pain during this phase. In the chronic phase the pain usually disappears and the curvature stabilizes. The plaque begins to harden and, although described, the curvature rarely resolves spontaneously [3]. Depending on the severity of the curvature, men with PD may find penetrative sexual intercourse difficult or impossible, causing psychological, emotional and relation problems [4]. Although surgical correction of the curvature remains the gold-standard treatment for PD, many conservative treatments have been pos- tulated, including extracorporeal shockwave therapy, iontophoresis and intralesional, topical and oral agents. None of this treatments have demonstrated its efficacy and safety in large, well designed clinical trials [5]. Surgical correction is indicated in men with estable disease unable to have penetrative sexual intercourse. Although the results of surgery in centers with experience correcting the curvature or penile deformity is usually excellent, the different procedures have collateral effects that may be undesirable (penile shortening, erectile dysfunction) [6]. The development of the collagenase of the Clostridium Histolyticum Collagenase of the Clostridium histolyticum (CCH; Xiapex ® , Swedish Orphan Biovitrum AB, Stockhom, Sweden; Xiaflex ® , Endo Pharmaceu- ticals, Malvern, PA, USA) is the first treatment approved by the US Food and Drug Administra- tion and the European Medicines Agency for the non-surgical management of PD. Collegenases are protease enzymes that under normal physi- ologic conditions hydrolyze collagen fibers. CCH contains a misture of class I and II collagenases in a defined ratio. Both classes act on different parts of the collagen molecule, allowing them to work synergistically. CCH has been found to work selectively on collagen types I and III, which are the predominant forms in PD, and spares collagen type IV, the main one found in arteries, veins and nerves. This selective nature of CCH lessens the chance of adjacent structures being affected [7]. The first in vitro experience about using CCH to treat PD was published in 1982, using Peyronie’s plaques of three men in addition to pericardial and corporal tissue. Histologic examination of the tissues found that CCH reduced the plaques and spared the arteries, nerves and elastic tissues, although there was some disruption to the collagen found in small venules [8]. Some years later, in 1985, Gelbard et al. con- ducted the first pilot study of intralesional CCH in 31 men with PD, who received an increasing dose of CCH due to the lack of adverse effects noted with the first and lower doses. They found an objective improvement in penile curvature in 20 men after completion of treatment. Of those men whose primary complaint was pain, 13 of 14 described resolution of that symptom after injection with CCH. A small corporal rupture man- aged conservatively was noted in one patient, but no other adverse effects were reported [9]. Gelbard et al. also conducted a further phase I prospective, randomized, placebo-controlled clinical trial published in 1993. They rand- omized 49 men to the treatment (CCH) and control (saline injection) groups. They stratified the participants in three categories according to the severity of the disease: category 1, with patients with a curvature ≤ 30º and/or palpable plaque less than 2 cm; category 2, with patients dispalying a curvature 30º to 60º and/or plaque size of 2 to 4 cm; and category 3, with patients >60º and/or plaque greater than 4 cm. The protocol consisted in one injection of a variable quantity of CCH or saline solution depending on the severity of the disease. A significant improvement in the angle of penile curvature and a reduction of the plaque size was found in the treatment group, with no adverse effects noted after 3-month follow-up [10]. Further evaluation of the safety and efficacy of CCH was investigated in a phase IIb double- blinded, randomized, controlled trial with 147 participants. They were randomized into four groups to receive CCH or saline placebo (3:1) with or without investigator penile modeling (1:1). Each cycle of treatment consisted of two injections (CCH or placebo) 24 to 72 hours apart, with each patient receiving three cycles separated by 6 weeks. Investigator modeling was performed 24 to 72 hours after the second injection of each treatment cycle. The mean decrease in curvature with CCH was 29% com- pared to 11% with placebo (p=0.001). A further decrease (32.4%) in curvature was found in men who underwent modeling after CCH injec- tion compared with worsening of 2.5% in the control group (p<0.001). No serious adverse events were noted [11]. Borja García Gómez Andrology and Reconstructive Urology Unit, Department of Urology Hospital Universitario 12 de Octubre Madrid, Spain borjagarciagomez@gmail.com Javier Romero Otero Andrology and Reconstructive Urology Unit, Department of Urology Hospital Universitario 12 de Octubre Madrid, Spain jromerootero@hotmail.com