Page 96 - Remedial Andrology

shortened protocol, longer PD duration, greater baseline PC and basal and dorsal plaque location were
identified as clinically significant predictors of treatment success [1049]. Accordingly, a nomogram developed
to predict treatment success after CCH for PD showed that patients with longer PD duration, greater baseline
penile curvature and basal plaque location had a greater chance of treatment success [1049]; however, these
findings need to be externally validated.

Regarding safety concerns, most PD patients treated with CCH experienced at least one mild or moderate
adverse reaction localised to the penis (penile haematoma (50.2%), penile pain (33.5%), penile swelling (28.9%)
and injection site pain (24.1%), which resolved spontaneously within 14 days of injection [1050]. The adverse
reaction profile was similar after each injection, regardless of the number of injections administered. Serious
treatment-emergent adverse events (TEAEs) (0.9%) include penile haematoma and corporeal rupture that require
surgical treatment. According to IMPRESS data and the shortened protocol, to prevent serious TEAEs men
should be advised to avoid sexual intercourse in the 4 weeks following injection. Recent preliminary data suggest
that treatment in the acute phase of the disease can be effective and safe [1010, 1044, 1045, 1051-1053].

In conclusion, CCH is a safe and established treatment for stable-phase disease. More recent evidence
suggests that CCH also has a role in affecting the progression of active-phase disease, thus supporting the
idea that the indications for CCH use could be expanded, although there is the possibility of a high placebo
effect. It should also be noted that there is a large effect of traction or modelling in controlled studies, while
studies reporting on modified protocols have small numbers of patients and are largely uncontrolled. Therefore,
patients should be counselled fully on the efficacy of collagenase and the high cost of treatment.

It has been suggested that those patients with severe curvature may also benefit from CCH injections because
of a potential downgrading of the penile curvature: a decrease in curvature may allow for a penile plication
procedure instead of a plaque incision and grafting procedure, therefore avoiding the more negative impact on
erectile function. However, further investigation is needed to validate these initial findings [1010, 1045].

The Panel has agreed to keep the whole set of information and recommendations regarding the use of CCH in
men with PD despite the recent official withdrawal of the product from the European market by the company.

Interferon α-2b
Interferon α-2b (IFN-α2b) has been shown to decrease fibroblast proliferation, extracellular matrix production
and collagen production by fibroblasts and improve the wound healing process from PD plaques in vitro [1054].
Intralesional injections (5x10^6 units of IFN-α2b in 10 mL saline every 2 weeks over 12 weeks for a total of six
injections) significantly improved penile curvature, plaque size and density, and pain compared to placebo.
Additionally, penile blood flow parameters are benefited by IFN-α2b [1040, 1055, 1056]. Regardless of plaque
location, IFN-α2b is an effective treatment option. Treatment with IFN-α2b provides a > 20% reduction in
curvature in most men with PD, independent of plaque location [1057]. Given the mild adverse effects, which
include sinusitis and flu-like symptoms, which can be effectively treated with NSAIDs before IFN-α2b injection,
and the moderate strength of data available, IFN-α2b is currently recommended for treatment of stable-phase
PD.

Steroids, hyaluronic acid and botulinum toxin (botox)
In the only single-blind, placebo-controlled study with intralesional administration of betamethasone, no
statistically significant changes in penile deformity, penile plaque size, and penile pain during erection
were reported [1058]. Adverse effects include tissue atrophy, thinning of the skin and immunosuppression
[1059]. Only a case-controlled single site study and a prospective non-controlled study supported the use of
hyaluronic acid injections in PD, with conflicting results related to penile curvature or penile pain [1060, 1061].
As only a single study evaluated intralesional botox injections in men with PD, the Panel conclude that there is
no robust evidence to support these treatments [1062].

8.2.3.1.3 Topical treatments
Topical verapamil and H-100 Gel
There is no sufficient and unequivocal evidence that topical treatments (verapamil, H-100 Gel [a compound
with nicardipine, superoxide dismutase and emu oil] or steroids) applied to the penile shaft, with or without the
use of iontophoresis (now known as transdermal electromotive drug administration), result in adequate levels of
the active compound within the tunica albuginea [1063-1066]. Therefore, the Panel does not support the use of
topical treatments for PD applied to the penile shaft.

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