sexual function [10,14]. Several minimally invasive therapy

options for PD exist; however, controlled data showing

cacy are limited [15].

Collagenase

Clostridium histolyticum

(CCH; Xia

ﬂ

; Auxilium

Pharmaceuticals, Inc., Chesterbrook, PA, USA) consists of two

microbial collagenases in a de

ned mass ratio, collagenases

AUX-I and AUX-II, which work synergistically to break down

collagen [16]. Intralesional injection therapy with CCH has been

approved by the US Food and Drug Administration for the

treatment of adult men with PD with palpable plaque and a

curvature deformity of

≥

at the start of therapy [16].

The clinical ef

cacy and safety of CCH intralesional injections

in subjects with PD have been demonstrated in early clinical

studies [17

–

19] as well as in the two large, identical, 52-week,

multicentre, phase III, double-blind, randomized, placebo-

controlled Investigation for Maximal Peyronie

’

s Reduction

cacy and Safety Studies (IMPRESS) I and II [20]. In these

studies, signi

cantly greater mean improvements were

observed in CCH-treated participants compared with those

receiving placebo on both of the co-primary endpoints of

penile curvature deformity (34 vs 18.2%, respectively;

0.001) and the PD symptom bother domain score

(2.8

3.8 vs 1.8

3.5, respectively;

0.004). Adverse

events (AEs) were typically mild or moderate and most resolved

without intervention within 14 days. The three most common

treatment-related AEs that occurred at a greater rate in the

treatment group than in the placebo group were penile

ecchymosis, penile swelling and penile pain [20].

Although these studies showed the ef

cacy and safety of CCH

in the treatment of PD, it is not known whether there are

patient characteristics that are predictors of treatment success.

The objective of the present

post hoc

analysis was to examine

the ef

cacy of CCH in subgroups of patients with PD from

IMPRESS I and II, de

ned by clinical characteristics.

Patients and Methods

Subgroups of patients from IMPRESS I and II were de

ned

according to four clinical variables of interest: baseline penile

curvature deformity; PD duration; degree of penile

calci

cation; and baseline erectile function severity. Two

groups of subjects were de

ned according to severity of penile

curvature deformity at baseline: 30

–

and 61

–

. Disease

duration was divided into the categories of 1

–

2 years,

2to

≤

4 years and

4 years. Penile X-ray or ultrasonography

ndings were used to determine the degree of plaque

calci

cation, and patients were categorized as having no

calci

cation, non-contiguous stippling, or contiguous

calci

cation that did not interfere with the injection (Patients

with calci

ed plaques that would interfere with injection had

been excluded from IMPRESS I and II.). For baseline erectile

function severity, patients were grouped by their baseline

International Index of Erectile Function (IIEF) score: 1

–

5 (no

sexual activity), 6

–

16 (low IIEF-erectile function), and

≥

(high IIEF-erectile function).

A full description of the methods and ethics protocols for

IMPRESS I and II is provided by Gelbard et al. [20]. Selected

inclusion criteria were: age

≥

18 years, being in a stable

relationship for

≥

3 months, diagnosis with PD symptoms for

≥

12 months with evidence of stable disease as determined by

the investigator, and penile curvature deformity of

. Enrolled patients were strati

ed by the degree of penile

curvature deformity (30

–

or 61

–

) and randomized 2:1

to CCH or placebo. During the screening period, each patient

had an assessment of plaque calci

cation by penile X-ray or

ultrasonography to determine if calci

cation might prevent

proper injection. Non-contiguous stippling of calcium and

plaque calci

cation were acceptable if these conditions did

not interfere with the injection of CCH.

Each treatment cycle consisted of two intralesional injections

of 0.58 mg CCH or placebo, with an interval of

–

72 h

between each injection. Approximately 24

–

72 h after the

second injection of each treatment cycle, patients in the CCH

and placebo groups underwent penile plaque modelling

(gradual, gentle stretching of the

ﬂ

accid penis in the opposite

direction of curvature) by the investigator. Patients were also

instructed to perform erect and

ﬂ

accid state modelling

activities at home daily for

6 weeks. The treatment cycle was

repeated after the 6-week at-home modelling period for up to

four treatment cycles (up to a total of eight injections). Patients

in the placebo groups in these two studies might be considered

‘

active

’

placebo subjects, because they received injections of

diluent, as well as home and investigator modelling.

The co-primary endpoint assessments were mean percent

change from baseline to week 52 in penile curvature

deformity and mean change from baseline to week 52 in PD

symptom bother domain score (assessed using the Peyronie

’

Disease Questionnaire [PDQ]; available at http://

www.auxilium.com/PDQ). Penile curvature deformity was

measured by goniometer using a standardized technique. PD

symptom bother domain score was determined by responses

to four questions in the PDQ regarding how bothered

subjects were by: the appearance of the erect penis; pain in

the erect penis; PD impact during intercourse; and PD impact

on decreased frequency of intercourse (total range: 0

–

16).

Data Analysis

The data from the identically designed IMPRESS I and II

were combined to improve statistical power in the evaluation

of subgroup responses to CCH treatment. The prede

ned

modi

ed intention-to-treat (mITT) population was included

in the primary ef

cacy analyses, and the mITT population

was used in the present analyses of subgroup responses to

CCH treatment. The mITT population (

612) included

651

cacy of collagenase

Clostridium histolyticum

in Peyronie

’

s disease