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Article of the Week: CCH in the Treatment of Peyronie’s disease

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Clinical Efficacy of Collagenase Clostridium Histolyticum in the Treatment of Peyronie’s Disease by Subgroups: Results From Two Large, Double-Blind, Randomized, Placebo-Controlled, Phase 3 Studies

Larry I. Lipshultz, Irwin Goldstein*, Allen D. Seftel, Gregory J. Kaufman, Ted M. Smith‡, James P. Tursi‡ and Arthur L. Burnett§

 

Scott Department of Urology, Baylor College of Medicine, Houston, TX, *San Diego Sexual Medicine, Alvarado Hospital, San Diego, CA,Cooper University Hospital, Camden, NJ, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, and §Johns Hopkins Medicine, Baltimore, MD, USA

 

OBJECTIVE

To examine the efficacy of intralesional collagenase Clostridium histolyticum (CCH) in defined subgroups of patients with Peyronie’s disease (PD).

PATIENTS AND METHODS

The efficacy of CCH compared with placebo, assessed from baseline to week 52, was examined in subgroups of participants from the Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies (IMPRESS) I and II. The subgroups were defined according to: severity of penile curvature deformity at baseline (30–60° [n = 492] and 61–90° [n = 120]); PD duration (1 to ≤2 [n = 201], >2 to ≤4 [n = 212] and >4 years [n = 199]); degree of plaque calcification (no calcification [n = 447], non-contiguous stippling [n = 103] and contiguous calcification that did not interfere with injection of CCH [n = 62]); and baseline erectile function (International Index of Erectile Function [IIEF] scores 1–5 [n= 22], 6–16 [n = 106] and ≥17 [n = 480]).

RESULTS

Reductions in penile curvature deformity and PD symptom bother were observed in all subgroups. Penile curvature deformity reductions were significantly greater with CCH than with placebo for the following subgroups: baseline penile curvature 30–60° and 61–90°; disease duration >2 to ≤4 years and >4 years; no calcification; and IIEF score ≥17 (high IIEF-erectile function score; P < 0.05 for all). PD symptom bother reductions were significantly greater in the CCH group for: penile curvature 30–60°; disease duration >4 years; no calcification; and IIEF score 1–5 (no sexual activity) and ≥17 (P < 0.05 for all).

CONCLUSIONS

In this analysis, clinical efficacy of CCH treatment for reducing penile curvature deformity and PD symptom bother was found across subgroups. In the IMPRESS I and II overall, adverse events (AEs) were typically mild or moderate, although treatment-related serious AEs, including corporal rupture or penile haematoma, occurred. Future studies could be considered to directly assess the efficacy and safety of CCH treatment in defined subgroups of PD patients, with the goal of identifying predictors of optimum treatment success.

Editorial: Intralesional Collagenase injections in PD patients : do they IMPRESS and can we afford them?

The study by Lipshultz et al. [1] is a post hoc reworking of the results of the Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies (IMPRESS) I and II phase 3 trials (each included 418 randomised patients) of intralesional injections of collagenase clostridium histolyticum (CCH) in patients with Peyronie’s disease (PD). The intention being to identify specifically, which subgroups of patients with PD might do best with CCH treatment compared with their matched placebo controls, as determined by reductions in penile curvature deformity and Peyronie’s Disease Questionnaire (PDQ) PD Symptom Bother score at study week 52 compared with baseline.

In both IMPRESS studies, CCH-treated patients showed statistically greater mean improvements vs placebo for reduction of penile curvature and PDQ PD Symptom Bother score. The current authors [1] have reassessed these previous results using four patient cohort variables, namely, baseline penile curvature, duration of PD, degree of penile calcification, and baseline erectile function severity, which were then further divided using various descriptors.

The results show that intralesional CCH significantly reduced baseline penile curvature in both the 30–60 and 61–90° curvature cohorts (P < 0.001 and P <0.008, respectively). Additionally, significant penile curvature improvements occurred with intralesional CCH when PD duration was >2 to <4 years and >4 years (P < 0.001).

CCH treatment in patients with PD with no penile calcification show statistically significant improvements in reducing baseline penile curvature and PDQ PD Symptom Bother score but this was not seen for either the noncontiguous stippling or contiguous calcification patient subgroups. Significant improvements in penile curvature occurred with intralesional CCH in patients with PD with a baseline International Index of Erectile Function (IIEF) score of >17 (P < 0.001) and the PDQ PD Symptom Bother score was also significantly reduced in these patients. Although these results are statistically meaningful, the clinical benefits are less readily discernible considering 12.5° was the largest difference in the reduction of mean penile curvature in all subgroups when comparing intralesional CCH to placebo at week 52. Similarly, although statistically significant changes in the PDQ PD Symptom Bother score were reported for intralesional CCH for the subgroups with duration of disease of >4 years, no penile calcification, and IIEF of >17, it is unclear what clinical benefit would accrue with a maximal change of 1.4 in any of the randomised subgroups.

Importantly, the IMPRESS I and II studies were not designed for subgroup analysis and despite combining these studies some of the specified PD subgroups contained in the present paper contain too few subjects to allow a valid statistical analysis of CCH efficacy. This has prompted the authors to conclude that further adequately powered prospective, randomised studies should be conducted to further clarify which PD characteristics offer optimal patient benefit with CCH treatment. The outcomes of these future studies might then optimise healthcare expenditure for a non-surgical treatment (consisting of eight penile injections and modelling), which shows therapeutic promise for patients with PD but potentially has significant consumer cost issues, which may be prohibitive unless some clinician guidelines exist for the use of CCH treatment. This has relevance as the USA Food and Drug Administration has already approved the use of intralesional CCH for the treatment of adult men with PD, who at the start of therapy have a palpable plaque and a curvature deformity of ≥30° [2].

Importantly, the outcomes of the patients with PD in the IMPRESS studies were only reported to week 52 of the study, which begs the questions as to how long any clinical benefit might last in patients who initially respond to intralesional CCH and whether these patients once having relapsed might respond to adjuvant injections.

 

Tim Terry
Department Urology, Leicester General Hospital, Leicester

 

References
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