Long-Term Safety and Curvature Deformity Characterization in Patients Previously Treated with Collagenase clostridium Histolyticum for Peyronie's Disease

Abstract

Purpose: We assessed the long-term safety and immunogenicity profile of collagenase clostridium histolyticum and characterized penile curvature deformity over time in patients previously treated for Peyronie's disease.

Materials and methods: This phase 4 study included men who received collagenase clostridium histolyticum in either 12-month, double-blind, placebo controlled clinical trials (IMPRESS I/II), or one of two 9-month open label studies. Eligible patients received no additional collagenase clostridium histolyticum treatment and were followed once yearly for up to 5 years to assess Peyronie's disease clinical symptoms, patient reported outcomes and safety.

Results: Of 280 patients enrolled 204 (73%) completed the study. At baseline 247 patients had already experienced a mean±SD penile curvature decrease from 51.8±15.0 to 31.0±16.1 degrees (improvement of 20.9±16.2 degrees or 39.5%). At year 5 in 180 patients, despite no additional treatment, there was an additional 9.1% improvement in mean penile curvature compared with reference data (4.3±13.4 degrees, 95% CI 2.3-6.2, p <0.02). At baseline 183 patients experienced mean Peyronie's Disease Questionnaire bother domain score improvement from 6.5±3.5 to 3.4±3.3. At year 5 there was additional score improvement to 2.4±2.9 (p=0.0003). Adverse events were reported in 17.5% (49) of patients but no adverse events were considered treatment related. No long-term safety issues were identified up to 5 years after treatment. Long-term immunogenicity profiling showed a decreasing trend in the number of anti-AUX-I and anti-AUX-II seropositive cases at years 4 and 5 after collagenase clostridium histolyticum treatment.

Conclusions: Most patients treated with collagenase clostridium histolyticum continued to have penile curvature and Peyronie's Disease Questionnaire domain score improvements through year 5 without additional collagenase clostridium histolyticum treatment, and no additional safety signals were identified.

Keywords: microbial collagenase; penile induration; safety; treatment outcome.