(031) Placebo Effect in Intralesional Injection Therapy for Peyronie’s Disease: A Systematic Review and Meta-Analysis of Published Prospective Clinical Trials

Introduction Intralesional injection therapy represents a cornerstone of the conservative management for Peyronie’s disease (PD), aiming to reduce penile curvature and plaque-related deformities through the localized administration of various pharmacological agents. Although multiple clinical trials have demonstrated curvature improvements following these interventions, the actual magnitude of curvature change attributable to the placebo effect-potentially mediated by the mechanical action of the needle-remains unclear. Objective This systematic review and meta-analysis aimed to quantify the curvature variation observed in the placebo arms of randomized controlled trials evaluating intralesional therapies for PD. Methods A systematic literature search was performed on PubMed and Scopus using the terms “Peyronie’s disease”, “induratio penis plastica”, “injection”, and “placebo” (PROSPERO ID n.159277). The search retrieved 1188 and 183 PubMed records, and 780 and 225 Scopus records for injection and placebo terms, respectively. Random-effects meta-analysis (REML-Hartung–Knapp adjustment) was conducted to estimate the standardized mean difference (SMD) in curvature change between baseline and end of therapy in placebo arms. A meta-regression model evaluated the influence of mean age, penile modeling and number of injections on curvature change. Risk of bias was assessed using the RoB 2 tool. Results After screening, 6 RCTs and 1 non-randomized controlled trial comparing active drug versus placebo were included with a total of 382 patients in placebo arms. The mean baseline curvature ranged from 33.5° to 50.9°, with follow-up durations between 4 and 52 weeks. The mean number of injection was 13.4. Across the seven included studies, placebo-treated patients experienced a modest but statistically significant reduction in penile curvature. The pooled mean difference was –5.1° (95%CI –8.0° to –2.3°; p=0.003), corresponding to an SMD of –0.38 (95%CI –0.55 to –0.20). No significant associations were observed between curvature change and mean age, number of injections, or penile modeling in meta-regression analyses. Risk of bias was overall moderate, mainly due to limited blinding and suboptimal randomization. Data on plaque size and pain were insufficient for pooled analysis. Conclusions This meta-analysis demonstrates that intralesional placebo injections alone are associated with an average curvature improvement of approximately 5 degrees. This effect size should be considered when designing and interpreting clinical trials investigating novel intralesional therapies for PD. Disclosure No