Collagenase Clostridium Histolyticum in the Treatment of Peyronie’s Disease: Review of a Minimally Invasive Treatment Option: Beyond the Abstract

In several well-designed clinical trials and post-approval studies, Collagenase clostridium histolyticum [(CCH), Xiaflex® Malvern, PA], has demonstrated both safety and efficacy in the management of Peyronie’s disease (PD) [1-3].  Intralesional injection of CCH using the protocol outlined in the phase III IMPRESS trials yielded, on average, a 34% reduction of penile curvature as well as improvements in the Peyronie’s Disease Questionnaire (PDQ) bother domains, which was superior to placebo [2].  In this review, our group highlights several important developments in the use of CCH in PD: 1) the potential of a new shortened modified treatment protocol, and 2) use of CCH in the treatment of atypical and acute phase disease.

In the standard protocol outlined by the IMPRESS (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) trials, each patient receives a total of eight injections, split into four cycles of two injections (0.58 mg), given 24-72 hours apart at six week intervals [2].  During the 24-72 hour post-injection period, either the patient or the physician performs penile modeling to enhance plaque disruption.  While this protocol has demonstrated clinical efficacy, there are several drawbacks. First, the standard protocol utilizes small concentrations of CCH, making it difficult to adequately distribute the drug over a wide area of the curvature apex. Second, intralesional injection of CCH causes a local inflammatory reaction that can make it difficult to palpate the plaque for the second injection after 24-72 hours. Furthermore, 24-72 hours may not be enough time for the inflammation at the injection site to subside before the next injection, potentially contributing to penile bruising and pain. Third, the standard protocol requires 14 patient visits over a 24-week period, which can be a significant burden on patients from a cost and time perspective.

A new shortened modified protocol was introduced and tested by Raheem et al. in 53 patients with PD, and the study represents a potential shift in the administration of this minimally invasive treatment option [4].  In this shortened protocol, each cycle consisted of only one injection with a larger dose of CCH (0.9 mg; whole vial). This method allows higher concentrations of CCH to be delivered to the plaque while limiting the inflammatory changes that occur with additional injections. Limiting the frequency of injections in the modified protocol and having patients complete the modeling themselves at home also allows patients to complete treatment with only four patient visits over a 12-week period. This undoubtedly improves compliance and reduces costs associated with CCH treatment. More importantly however, this shortened modified protocol demonstrated a mean curvature reduction of −17.4° (−31.4%) from baseline, which is comparable to the results obtained in the IMPRESS trials [2, 4]. Moreover, there was an improvement in each of the International Index of Erectile Function (IIEF) questionnaire domains, all 3 PDQ domains, and the global assessment of the PDQ.

CCH continues to be a gold standard minimally invasive treatment for PD; however due to its cost and adherence to completing all four cycles, it can be logistically difficult for some patients.  The new shortened modified protocol addresses these issues without sacrificing clinical efficacy by reducing curvature and improving PDQ bother domains.

In addition to new developments in the administration protocol, studies are starting to increasingly broaden inclusion criteria to include patients with acute phase disease and atypical plaques.  In a recent study published by our group, we found that the use of CCH in the acute phase of PD had similar safety and efficacy outcomes compared to those treated in the stable phase of the disease [5].  Additionally, studies are starting to utilize CCH to treat atypical presentations of PD, including ventral plaques, hourglass deformities, and multiplanar plaques.  Roughly 10% of patients present with atypical PD and suffer greater burden of disease than typical PD counterparts.  Milam et al. administered four cycles of CCH to two patients with ventral plaques and saw significant improvement in penile curvature without serious adverse events [6].  These studies show promise that CCH can be safely given to patients that do not meet the inclusion criteria outlined in the IMPRESS trials.

Further randomized-controlled studies assessing the durability of the shortened modified protocol and the use of CCH in acute phase and atypical PD are warranted.

References:

  1. Gelbard M, Lipshultz L, Tursi J, Smith T, Kaufman G, Levine L. Phase 2b study of the clinical efficacy and safety of collagenase clostridium histolyticum in patients with Peyronie disease. J Urol 2012; 187:2268–2274.
  2. Gelbard M, Goldstein I, Hellstrom W, McMahon C, Smith T, Tursi J, Jones N, Kaufman G, Culley C. 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. J Urol 2013;190: 199–207.
  3. Levine LA, Cuzin B, Mark S, Gelbard MK, Jones NA, Liu G, Kaufman GJ, Tursi JP, Ralph DJ. Clinical safety and effectiveness of collagenase Clostridium histolyticum injection in patients with Peyronie’s disease: a phase 3 open-label study. J Sex Med. 2015;12(1):248–258.
  4. Abdel Raheem A, Capece M, Kalejaiye O, Abdel-Raheem T, Falcone M, Johnson M. Safety and effectiveness of collagenase clostridium histolyticum in the treatment of Peyronie’s disease using a new modified shortened protocol. BJU Int 2017. doi: 10.1111/bju.13932.
  5. Nguyen T, Anaissie J, DeLay K, Yafi F, Sikka S, Hellstrom WJG.  Safety and Efficacy of Collegase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease.  Journal of Sexual Medicine 2017. doi: 10.1016/j.jsxm.2017.08.008.
  6. Milam D. 116. Positive results with collagenase clostridium histolyticum treatment in two patients with ventral penile curvature due to Peyronie’s disease. J Sex Med 2016;13:S55.

Written by: Andrew T. Gabrielson, Laith M. Alzweri, Wayne J.G. Hellstrom, Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA

Corresponding Author: Wayne J.G. Hellstrom, MD, FACS, Tulane University School of Medicine, Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA

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