INTRODUCTION
Cutaneous tolerability is a significant concern for any
acne therapy and has played an important role in the
development of topical retinoids. The hydroalcoholic
formulation of tretinoin, the first topical retinoid to become
available, caused considerable levels of cutaneous irritation including
redness, scaling, burning, and itching, primarily in the
first few weeks of therapy.1-7 Although tretinoin was effective
in reducing both comedones and inflammatory lesions, tolerability
issues affected the tretinoin risk/benefit balance so that it
was generally regarded as a second-line therapy and reserved
for patients with non-inflammatory acne and those for whom
antibiotic monotherapy failed.8
Development of various formulations and concentrations of
tretinoin ensued, and as tretinoin concentrations progressively
decreased in gels from 0.05% to 0.025% to 0.01%, in creams
from 0.1% to 0.05% to 0.025%, and most recently in microsphere
formulations,9 tretinoin’s tolerability progressively increased.
In addition to new tretinoin formulations, other topical
retinoid formulations with improved tolerability were also developed,
such as adapalene.10-15 However, most dermatologists
still find the tolerability of topical retinoids to be problematic.8
Several variables have been found to affect retinoid tolerability,
including retinoid concentration, skin sensitivity and the vehicle
(cream or gel), with the latter’s effect on tolerability varying
depending on the specific retinoid.16
A novel gel formulation that combines clindamycin and tretinoin
was recently approved by the FDA for treating mild-to-moderate acne (CLIN/RA). CLIN/RA consists of a crystalline suspension of
clindamycin 1.2% (CLIN) in combination with 0.025% tretinoin
(RA) gel. Trials of CLIN/RA suggest that it may not provoke the
degree of irritation associated with standard solubilized formulations
of tretinoin.17 The current study provides a further
evaluation of the irritancy and tolerability profile of CLIN/RA in
comparison to 0.1% tretinoin gel or 0.1% adapalene gel.
METHODS
This was a safety/tolerability study. Due to the short length of
therapy (21 days), efficacy evaluations were not conducted.
The study’s inclusion criteria are shown in Table 1. Forty-five patients
with active acne volunteered to participate in this study
and were randomized to enroll in a bilaterally paired comparison
between products applied to the right and left sides of the
face. Patients with a history of unusual skin reactions to tretinoin
products or other topical retinoids, or any sensitivity to the
test article components, were excluded.
Patients were randomly assigned to apply two of three products,
with one side of the face treated with CLIN/RA and the
contralateral side of the face treated with either tretinoin 0.1%
(n=23) or adapalene 0.1% (n=22). The 0.1 % tretinoin was selected
because of its extensive use in the microsponge. Tretinoin
has been the mainstay of topical retinoid therapy for decades.3
Treatments were applied once daily (including weekends) for
21 days. Treatment application on Monday through Friday was
supervised at the test facility, and Saturday and Sunday was
applied, unsupervised, at the patient’s home. Patients applied
