Comparative Effectiveness of Intralesional Therapy for Peyronie’s Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis

Giorgio Ivan Russo, MD, PhD; Giovanni Cacciamani, MD; Andrea Cocci, MD; Thomas M. Kessler, MD; Giuseppe Morgia, MD; Ege Can Serefoglu, MD, FECSM; Maarten Albersen, MD, PhD; Paolo Verze, MD, PhD, on behalf of EAU-YAU Men’s Health Working Group

FIRST PUBLISHED: January 25, 2019 – The Journal of Sexual Medicine

DOI: https://doi.org/10.1016/j.jsxm.2018.12.011

Introduction

Intralesional injection therapy with collagenase Clostridium histolyticum (CCH) is approved by the U.S. Food and Drug Administration and the European Medicines Agency for the non-surgical treatment of Peyronie’s disease. However, few studies have used standardized methods to compare CCH to placebo or other intralesional drug regimens.

This study is a network meta-analysis (NMA) that aims to compare the clinical efficacy of intralesional therapies for Peyronie’s disease. Randomized controlled trials were analyzed based on improvement of penile curvature (PC) and erectile function.

Methods

Relevant studies published until September 30, 2017 were identified through a search of the Medline, Scopus, and Web of Science databases. Four intralesional therapies were considered: CCH, hyaluronic acid, verapamil, and interferon α-2b.

The primary efficacy outcome was the change in PC from baseline to final follow up. The secondary outcome was the change in the erectile function domain score of the International Index of Erectile Function (IIEF) from baseline to study end.

Risk analysis was used to assess quality of evidence as high, moderate, low, and very low. Quality of evidence was based on 5 domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias.

Results

Eight studies including 1,050 patients overall were reviewed.

The participants’ ages ranged from 52.0 to 58.2 years. Mean follow-up ranged from 3 – 13 months.

The following results were reported:

• Penile curvature (degree). 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).
• Improvement in erectile function. 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).

Discussion

This is the first meta-analysis to compare all 4 intralesional drugs.

If a patient’s priority is improving penile curvature, then CCH and interferon α-2b appear to be the most effective treatment choices. In contrast, men who prioritize erectile function may do better with hyaluronic acid treatment.

Because of a lack of homogeneity across the studies, further information on other outcomes (i.e., pain, plaque size, and patient satisfaction) is unknown. Also, a meta-regression analysis of predictive factors of treatment response was not determined because of the low number of included studies. Adverse effects were not reported.

Implications for the Future

“On the basis of this NMA, empirical therapy for [Peyronie’s disease] should be avoided to offer the patients the best treatment in terms of level of evidence,” the authors wrote.

They added, “Urologists should discuss medical therapy with patients before surgical correction, as well as the target of improvement that they expect to obtain.”

Further research and placebo-controlled prospective clinical trials were recommended.