Peyronie’s Disease: Should Nonresponders Receive Entire CCH Injection Protocol?

Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie’s Disease Men

Manaf Alom MBBS; Holli Burgon BS; Matthew Ziegelmann MD; Tobias Köhler MD; Sevann Helo MD; Landon Trost MD

FIRST PUBLISHED: May 18, 2021 – The Journal of Sexual Medicine

DOI: https://doi.org/10.1016/j.jsxm.2021.03.075

Introduction

Injections of collagenase Clostridium histolyticum (CCH) are an effective way to treat Peyronie’s disease. Typically, 8 injections are administered over a period of several months. The protocol includes up to 4 series consisting of 2 injections each.

However, results can vary, and some patients do not have significant improvements after the first series of injections. It is unclear whether men who do not respond well at first should continue with the entire course of treatment.

The current study examined the results of men receiving 4 series of CCH injections to determine whether continuing treatment is worthwhile for initial nonresponders.

Materials and Methods 

The study period ran from January 2014 to February 2019. Injections were administered at the point of maximum curvature.

In total, men received 8 injections, administered in 4 series spaced at least six weeks apart. Each series consisted of 2 injections, which were spaced 24 to 72 hours apart.

During each 6-week interval, men were instructed to do penile modeling and traction therapy at home. This protocol changed over time. In late 2018, men took sildenafil daily during their CCH injections.

Patients were advised not to have penetrative intercourse for 4 weeks after each series of injections.

Assessments were conducted at baseline, immediately before the third series (interval assessment) and 6 weeks after the fourth series (final assessment).

Men were also categorized based on degrees of improvement:

• ≤ 10 degrees or > 10 degrees
• ≤ 20% or > 20%

Results 

Data was collected for 296 men treated with CCH. The participants’ mean age was 56.6 years, and they had had Peyronie’s disease for an average of 28.6 months. Their mean baseline curvature was 63.4 degrees.

The overall curvature improvement was -21.5 degrees. About 64% of the men had a curvature improvement greater than 25%, and a quarter of the men experienced a curvature improvement greater than 50%.

For comparisons of the first and second series with the third and fourth series, the following results were reported:

• “The extent of response to the first 2 series of injections was strongly correlated with subsequent outcomes from the final 2 series of injections.
• “Results demonstrate that among men who achieved ≤10° improvements during the first 2 series, the mean subsequent improvement was 15.2° (22.2%), while those who had >10° improvements initially, on average, experienced no additional improvements with the subsequent two series.
• “Similarly, those who ultimately achieved >10° or >20% during the final 2 series of injections were those who had minimal improvements during the initial 2 series (mean improvement of 1.4° and 7.7°, respectively).
• “In contrast, those who experienced <10° or ≤20% improvements during the final 2 series had already experienced significant improvements during the first 2 series (mean 24° and 22.5°, respectively).
• “However, when evaluating the subgroup of men who achieved >10° during the first 2 series, 31% went on to experience further absolute improvements during the final 2 series, 22% improved by ≥10°, and 24% improved by ≥20%.
• “In contrast, among those who achieved ≤10° during the first 2 series, 70% achieved further absolute improvements, 64% improved by ≥10°, and 64% improved by ≥20%.
• “Overall, men who had ≤20% improvements during the initial 2 series were 2.7x more likely to subsequently experience >20% improvements during the final 2 series compared to those who initially achieved >20% curve improvement after 2 series.”

Discussion 

Many men who do not respond well after the first and second CCH injection series do have improvements with the third and fourth series.

In contrast, men who do respond well after the first and second CCH injection series may not have significant improvements after the third and fourth series. However, in this study, about a third of men who responded well at first went on to have further significant improvements.

The results might be explained by several possible factors:

• Men with extensive fibrosis may need more medication before a response is evident.
• Men may need more time to learn penile modeling techniques.
• Drug administration factors, such as depth of injection, might play a role.

Several limitations were acknowledged. For example, the study included only men who had received all eight CCH injections. Men who stopped their treatment early may have had different results. In addition, results pertain to just one institution and may not necessarily apply to men treated in other locations and with other protocols.

Conclusion

“These data are clinically important, as they may help to guide practicing clinicians on the important question as to whether or not to continue administering CCH injections to men who are initially non-responders.”