{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:02Z","timestamp":1753891562644,"version":"3.41.2"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Peyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial, which propelled us to conduct the first evidence-based research on this topic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched the Web of Science, PubMed, Embase, and <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link> for related randomized controlled trials (RCTs). A systematic review and meta-analysis were performed to compare the penile curvature deformity (PCD), Peyronie's Disease Questionnaire peyronie's disease symptom bother (PDSB), penile pain score, total treatment-related adverse events (TAEs), and specific adverse events, including penile pain, penile edema, injection site pain, and contusion. Cochrane Collaboration's tool and Review Manager 5.3.0 version were applied, respectively, to evaluate the study quality and heterogeneity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four articles (five RCTs) with 1,227 patients were finally included in the meta-analysis. The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: \u2212318.77, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and PDSB (WMD: \u22121.20, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) compared to the placebo group, but there was no difference in the penile pain score (WMD: \u22120.64, <jats:italic>P<\/jats:italic> = 0.39) between the two groups. Furthermore, the incidence of TAEs in the CCH group was higher [odds ratio (OR): 12.86, <jats:italic>p<\/jats:italic> &amp;lt; 0.001].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current evidence suggests that CCH has a significant effect on treating PD. Considering that all these adverse events are acceptable and curable, CCH could slow the disease progression in the acute phase or act as a substitute for patients unable or unwilling to undergo surgery. However, the conclusion could not be certainly drawn until RCTs with a larger scale proved it.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.780956","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T05:38:20Z","timestamp":1645162700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Safety of Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease: An Evidence-Based Analysis"],"prefix":"10.3389","volume":"9","author":[{"given":"Dehong","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinze","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinzhi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangren","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/andr.12058","article-title":"Therapeutic advances in the treatment of Peyronie's disease","volume":"3","author":"Yafi","year":"2015","journal-title":"Andrology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s11934-020-01025-7","article-title":"The management of penile fracture: a review of the literature with special consideration for patients undergoing collagenase clostridium histolyticum injection therapy","volume":"22","author":"Hughes","year":"2021","journal-title":"Curr Urol Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1046\/j.1464-4096.2001.02436.x","article-title":"The prevalence of Peyronie's disease: results of a large survey","volume":"88","author":"Schwarzer","year":"2001","journal-title":"BJU Int."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1097\/01.ju.0000127744.18878.f1","article-title":"Subjective and objective analysis of the prevalence of Peyronie's disease in a population of men presenting for prostate cancer screening","volume":"171","author":"Mulhall","year":"2004","journal-title":"J Urol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"282503","DOI":"10.1155\/2011\/282503","article-title":"A population-based study of Peyronie's disease: prevalence and treatment patterns in the United States","volume":"2011","author":"Dibenedetti","year":"2011","journal-title":"Adv Urol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.jsxm.2016.04.062","article-title":"Evidence-based management guidelines on Peyronie's disease","volume":"13","author":"Chung","year":"2016","journal-title":"J Sex Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11934-018-0800-5","article-title":"Contemporary review of Peyronie's disease treatment","volume":"19","author":"Capoccia","year":"2018","journal-title":"Curr Urol Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.eururo.2018.07.005","article-title":"Clinical efficacy of injection and mechanical therapy for Peyronie's disease: a systematic review of the literature","volume":"74","author":"Russo","year":"2018","journal-title":"Eur Urol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/s41585-018-0117-7","article-title":"Nonsurgical management of Peyronie's disease","volume":"16","author":"Tsambarlis","year":"2018","journal-title":"Nat Rev Urol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s11934-014-0459-5","article-title":"2013-2014 updates in Peyronie's disease management","volume":"15","author":"Sherer","year":"2014","journal-title":"Curr Urol Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.aju.2013.03.008","article-title":"Peyronie's disease: a contemporary review of non-surgical treatment","volume":"11","author":"Levine","year":"2013","journal-title":"Arab J Urol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1756287218823671","DOI":"10.1177\/1756287218823671","article-title":"Non-invasive treatment in the management of Peyronie's disease","volume":"11","author":"Randhawa","year":"2019","journal-title":"Ther Adv Urol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"380","DOI":"10.23736\/S0393-2249.18.03118-1","article-title":"Collagenase clostridium histolyticum: a novel medical treatment for Peyronie's disease","volume":"70","author":"Abdel Raheem","year":"2018","journal-title":"Minerva Urol Nefrol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1177\/1756287214537331","article-title":"Experience in the use of collagenase clostridium histolyticum in the management of Peyronie's disease: current data and future prospects","volume":"6","author":"Egui Rojo","year":"2014","journal-title":"Ther Adv Urol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1111\/bju.13120","article-title":"Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD)","volume":"116","author":"Carson","year":"2015","journal-title":"BJU Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1111\/bju.14410","article-title":"Predictors of treatment success after collagenase Clostridium histolyticum injection for Peyronie's disease: development of a nomogram from a multicentre single-arm, non-placebo controlled clinical study","volume":"122","author":"Cocci","year":"2018","journal-title":"BJU Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Bmj."},{"key":"B18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S0022-5347(17)35998-0","article-title":"Collagenase versus placebo in the treatment of Peyronie's disease: a double-blind study","volume":"149","author":"Gelbard","year":"1993","journal-title":"J Urol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2268","DOI":"10.1016\/j.juro.2012.01.032","article-title":"Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease","volume":"187","author":"Gelbard","year":"2012","journal-title":"J Urol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.juro.2013.01.087","article-title":"3rd: 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","volume":"190","author":"Gelbard","year":"2013","journal-title":"J Urol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/bju.13096","article-title":"Clinical efficacy of collagenase Clostridium histolyticum in the treatment of Peyronie's disease by subgroup: results from two large, double-blind, randomized, placebo-controlled, phase III studies","volume":"116","author":"Lipshultz","year":"2015","journal-title":"BJU Int."},{"key":"B22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.sxmr.2015.10.002","article-title":"The genetic basis of peyronie disease: a review","volume":"4","author":"Herati","year":"2016","journal-title":"Sex Med Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.juro.2015.10.065","article-title":"Restoration of penile function and patient satisfaction with intralesional collagenase clostridium histolyticum injection for Peyronie's disease","volume":"195","author":"Ziegelmann","year":"2016","journal-title":"J Urol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.juro.2014.02.1853","article-title":"Pd22-02 meaningful change in peyronie's disease following treatment with collagenase clostridium histolyticum: results from two large double-blind, randomized, placebo-controlled phase 3 studies","volume":"12","author":"Hellstrom","year":"2014","journal-title":"J Urol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.urology.2015.04.047","article-title":"Self-report and clinical response to peyronie's disease treatment: Peyronie's disease questionnaire results from 2 large double-blind, randomized, placebo-controlled phase 3 studies","volume":"86","author":"Hellstrom","year":"2015","journal-title":"Urology."},{"key":"B26","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s00345-019-02850-3","article-title":"Characteristics predictive of response to collagenase clostridium histolyticum for Peyronie's disease: a review of the literature","volume":"38","author":"Masterson","year":"2020","journal-title":"World J Urol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.urology.2017.05.029","article-title":"Factors associated with erectile dysfunction and the Peyronie's disease questionnaire in patients with peyronie disease","volume":"107","author":"Serefoglu","year":"2017","journal-title":"Urology."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1001\/jama.2020.14819","article-title":"Peyronie disease","volume":"324","author":"Gaffney","year":"2020","journal-title":"Jama."},{"key":"B29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41443-018-0063-1","article-title":"Limited success with clostridium collagenase histolyticum following FDA approval for the treatment of Peyronie's disease","volume":"31","author":"Tsambarlis","year":"2019","journal-title":"Int J Impot Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.jsxm.2016.02.105","article-title":"Results of SMSNA survey regarding complications following intralesional injection therapy with collagenase clostridium histolyticum for Peyronie's disease","volume":"13","author":"Yafi","year":"2016","journal-title":"J Sex Med."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.780956\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T05:38:22Z","timestamp":1645162702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.780956\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":30,"alternative-id":["10.3389\/fmed.2022.780956"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.780956","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"article-number":"780956"}}