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Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future Impact: Beyond the Abstract

Intralesional injection of collagenase clostridium histolyticum (CCH) has become the gold standard for minimally invasive treatment of stable phase Peyronie’s disease (PD).  Through years of well-designed clinical trials and post-approval studies involving over 1,500 patients, CCH continues to demonstrate clinical efficacy by decreasing penile curvature and plaque consistency, as well as improving sexual function and quality of life in patients with PD [1-5].

The study protocol for the IMPRESS trials required >1 year of stable disease prior to initiation of intralesional CCH injections, and the American Urological Association (AUA) guidelines currently recommend that clinicians start therapy during the stable phase of PD, when pain has subsided and there is no progression of curvature [6].  However, the ideal time to initiate intralesional CCH therapy remains unknown, and whether treatment can be initiated during the acute phase of PD is often a topic of debate. There is a lack of well-designed clinical trials that document outcomes of patients treated during the acute phase; however studies are beginning to incorporate patients who meet the acute phase criteria.  Recently published data substantiates that the use of intralesional CCH in the acute phase of PD is both safe and effective in modifying disease progression [7-8].  These studies involved small sample sizes; however their results provide a framework for future investigations.

The IMPRESS trials also excluded patients with ventral Peyronie’s plaques due to potential risk of urethral injury during penile modeling.  One recent study reported outcomes of two patients being treated with CCH for ventral plaques.  Both patients demonstrated marked improvement of symptoms with minimal adverse events [9].  

CCH is also being investigated as a potential treatment of urethral stricture disease (USD), a fibroproliferative disease that shares many pathophysiologic similarities with PD.  Urethral injection of CCH has demonstrated dose-dependent decreases in collagen expression and urethral obstruction in a rat model of urethral fibrosis [10].  Of note, urethral injection of CCH in these rats demonstrated excellent tolerability with no severe adverse events specific to the urethra. Given the tolerability of urethral injection of CCH, the current contraindication of using CCH in patients with complex ventral Peyronie’s plaques may also be worth revisiting.

CCH continues to be the mainstay for non-surgical management of stable phase PD.  However, its utility in the management of acute phase PD, PD with ventral plaques, and other urologic conditions—such as USD—is still evolving.

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

*Corresponding Author

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References:
  1. Gelbard M, James K, Riach P, Dorey F. Collagenase versus placebo in the treatment of Peyronie’s disease: a double-blind study. J Urol 1993; 149:56–58.
  2. Jordan G. The use of intralesional clostridial collagenase injection therapy for Peyronie’s disease: a prospective, single-center, non-placebo-controlled study. J Sex Med 2008; 5:180–187.
  3. 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.
  4. 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.
  5. 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.
  6. Nehra A, Alterowitz R, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh JJ, Khera M, Kirkby E, McVary KT, Miner MM, Nelson CJ, Sadeghi-Nejad H, Seftel AD, Shindel AW, Burnett AL; American Urological Association Education and Research, Inc. Peyronie’s Disease: AUA Guideline. J Urol. 2015;194:745–53.
  7. Yang KK, Bennett N. Peyronie's Disease and Injectable Collagenase Clostridium histolyticum: Safety, Efficacy, and Improvements in Subjective Symptoms. Urology 2016;94:143-7.
  8. Anaissie J, Yafi F, DeLay KJ, Traore EJ, Sikka SC, Hellstrom WJG. Impact of Number of Cycles of Collagenase Clostridium Histolyticum on Outcomes in Patients With Peyronie's Disease. J Urol 2017; 100:125-130.
  9. Milam D.  Positive Results with Collagenase Clostridium histolyticum Treatment in Two Patients with Ventral Penile Curvature Due to Peyronie’s Disease. 21st Annual Fall Meeting of Sexual Medicine Society of North American. 2015, abstract 116.
  10. Sangkum P, Yafi FA, Kim H, Bouljihad M, Ranjan M, Datta A, Mandava SH, Sikka SC, Abdel-Mageed AB, Moparty K, Hellstrom WJ. Collagenase Clostridium histolyticum (Xiaflex) for the Treatment of Urethral Stricture Disease in a Rat Model of Urethral Fibrosis. Urology. 2015;86(3):647.e1-647.e6