Introduction: Medical treatment of Peyronie's disease (PD) in terms of intralesional therapy is still a matter of debate. Aim: To compare the efficacy of different classes of intralesional therapy with a network meta-analysis (NMA) method. Methods: The search was conducted using documents published in PubMed, Scopus, and Web of Science databases until September 30, 2017. We included randomized controlled trials comparing at least 1 intralesional therapy with a placebo therapy or with another drug for the treatment of PD. All intralesional therapies have been considered: collagenase Clostridium histolyticum (CCH), hyaluronic acid, verapamil, and interferon α-2b. Main Outcome Measure: Outcomes of the study are the mean change in penile curvature (PC) and in erectile function (EF) assessed with the International Index of Erectile Function questionnaire. Results: In total, 8 comparisons matched with the inclusion criteria, which includes 1,050 patients. With regard to PC (degree) improvement, hyaluronic acid and verapamil showed worse outcomes when compared with CCH (−6.66 and −2.30) and interferon α-2b (−6.75 and −2.38). When considering improvement in EF, hyaluronic acid, verapamil and interferon α-2b showed a slight increase in mean change when compared with CCH (+2.39, +1.77, and +0.65). Moreover, verapamil and interferon α-2b showed slightly worse mean change in comparison to hyaluronic acid (+0.62 and +1.74), whereas interferon α-2b was worse than verapamil (−1.12). Clinical Implications: Based on this NMA, empirical therapy for PD should be avoided to offer the patients the best treatment in terms of level of evidence. Strengths & Limitations: In this NMA, we have provided, for the first time, evidence of the efficacy between different intralesional therapies for the treatment of PD. We were not able to compare all specific outcomes (ie, pain, plaque size, patient satisfaction) of PD, because of the lack of homogeneity across relevant studies. Moreover, because of the few included studies, a meta-regression analysis of predictive factors of treatment response was not calculated. Conclusion: This is the first meta-analysis comparing all available intralesional treatments for PD. CCH and interferon α-2b showed the best outcome in terms of PC, whereas hyaluronic acid was most efficient in relation to EF. Russo GI, Cacciamani G, Cocci A, et al. Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis. J Sex Med 2019;16:289–299.
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