size reduction and improvement of curvature in patients

treated with vitamin E who had plaques

500 mm

Signi

cant bene

ts of vitamin E on plaque size reduction

were not observed in patients with plaques

≤

500 mm

although the authors hypothesize that this may have been

attributable to low sample size and statistical power [21].

In a prospective, randomized, double-blind, placebo-

controlled study of CCH in 49 men with PD, signi

cant

improvements in plaque size and penile deformity were

observed overall with CCH treatment compared with placebo

[18]. The men were divided into three groups for analysis: (i)

those with a penile bend of

≤

and/or palpable plaque

2cm(

7); (ii) those with a penile bend of 30

–

and/or

–

4 cm of palpable plaque (

24); and (iii) those with a

penile bend of

and/or

4 cm of palpable plaque (

18)

[18]. Signi

cant differences between CCH and placebo were

observed in the second two groups but not the

rst, although

this may have been attributable to the small number of men

in that group.

In addition to a lack of studies that examine the potential for

differential ef

cacy in patients with PD based on their clinical

characteristics, there has been a paucity of well controlled studies

supporting effective treatments for PD in general [9,14].

Minimally invasive treatments that have been used for PD

include topical agents, oral systemic agents, mechanical

stretching, extracorporeal shock wave therapy, electromotive

drug administration/iontophoresis and intralesional injection [9].

Generalization of the results of the present study is limited by

the

post hoc

nature of the analyses, as well as the small

sample sizes in some of the subgroups, as these studies were

not powered for this purpose. In addition, the limitations of

the original IMPRESS in providing clinical guidance extend to

the present analysis in terms of the types of patients who

were allowed to participate in the study and the duration of

the study; however, the present analysis was performed on

data from IMPRESS I and II, which could be considered the

most rigorous CCH treatment trials to date [20]. The rigour

of the studies and the large combined sample size support the

ndings of the subanalyses reported in the present paper.

Because the subgroups in the present study were drawn from

a pre-existing study population, there was large variation in

the sizes of the subgroups, with a range from 22 patients

(IIEF scores 1

–

5 [no sexual activity]) to 492 patients (baseline

penile curvature deformity of 30

–

) in one group. In the

present analysis, clinical ef

cacy of CCH treatment for

reducing penile curvature deformity and PD symptom bother

was found across subgroups, and statistically signi

cant

ndings were observed consistently in the three largest

subgroups, with less consistent

ndings in the smaller

subgroups. These

post hoc

analyses therefore provide

additional support for the overall

ndings of IMPRESS I and

II, and also indicate that further studies with adequate

statistical power to examine each of these individual groups

should be considered, with the goal of determining whether

there are patient variables that can be used to guide treatment

decisions.

In conclusion, CCH is a novel, non-surgical, minimally

invasive treatment for PD. Intralesional injection therapy with

CCH has been approved by the US Food and Drug

Administration for the treatment of adult men with PD with

a palpable plaque and curvature deformity of at least 30

the start of therapy [16]. In IMPRESS I and II, signi

cant

improvement in penile curvature deformity and PD symptom

bother were observed in CCH-treated patients compared with

placebo [20]. The AEs observed were typically mild or

moderate, although treatment-related serious AEs, including

corporal rupture or penile haematoma, occurred in six

patients. All three AEs of corporeal rupture occurred during

intercourse and were repaired surgically. One AE of penile

haematoma resolved spontaneously, one was treated with

aspiration and one cystic haematoma was noted not to

involve tunical defect at Nesbit plication surgery. In the

present analysis, clinical ef

cacy of CCH treatment for

reducing penile curvature deformity and PD symptom bother

was found across various patient subgroups; however, a

consistent pattern of statistically signi

cant differences did

not emerge. These exploratory analyses provide additional

support for the ef

cacy of CCH in the treatment of PD, and

also indicate that further studies should be considered to

identify clinical predictors of optimum treatment success with

CCH treatment.

Acknowledgements

The authors thank Jennifer Steeber, PhD, of MedVal

Scienti

c Information Services, LLC, for providing medical

writing and editorial assistance. This manuscript was

prepared according to the International Society for Medical

Publication Professionals

’‘

Good Publication Practice for

Communicating Company-Sponsored Medical Research: The

GPP2 Guidelines.

’

Con

ﬂ

ict of Interest

Larry I. Lipshultz is an investigator and speaker for

Auxilium Pharmaceuticals, Inc., Eli Lilly, and Endo

Pharmaceuticals, a consultant/advisor for Repros

Therapeutics, has participated in a scienti

c study/trial for

Allergan, and is a speaker for American Medical Systems.

I.G. is a consultant for or has received honoraria from

AbbVie, Allergan, Apricus, Ascend, Auxilium

Pharmaceuticals, Inc., Coloplast, Exploramed, Eli Lilly,

Emotional Brain, Merck, Neogyn, P

zer, Shionogi, Sprout,

Strategic Science & Technologies and is an investigator for

Afferent, Allergan, American Medical Systems, Auxilium

Pharmaceuticals, Inc., Clarus, Emotional Brain, Ferring,

655

cacy of collagenase

Clostridium histolyticum

in Peyronie

’

s disease