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Successful Treatment of Acne Vulgaris Using a New Method
Results of a Randomized Vehicle-Controlled Trial of Short-Contact Therapy With 0.1% Tazarotene Gel
Susan Bershad, MD;
Giselle Kranjac Singer, BS;
Janice E. Parente, PhD;
Mei-Heng Tan, MD;
Daniel W. Sherer, MD;
Andrea N. Persaud, MD;
Mark Lebwohl, MD
Arch Dermatol. 2002;138:481-489.
ABSTRACT
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Context Short-contact application of 0.1% tazarotene gel for acne was devised
to minimize local adverse effects. Its efficacy and safety are unknown.
Objectives To assess acne improvement and tolerability during 12 weeks of short-contact
treatment with 0.1% tazarotene gel vs a nonmedicated gel control.
Design A randomized, masked, vehicle-controlled trial.
Setting Outpatient facilities at an urban medical school and an affiliated suburban
office practice.
Participants Ninety-nine volunteers with facial acne were enrolled; 81 completed
the study.
Intervention Thirty-three patients were randomly assigned to each of 3 groups: T
+ T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene
gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice
daily. Patients adjusted the contact period as tolerated, between 30 seconds
and 5 minutes per application.
Main Outcome Measures Acne efficacy by reduction in acne lesions, treatment success (50%-100%
improvement in global response to treatment) and improvement in overall disease
severity. Local adverse effects, scored from none to severe.
Results By week 12, T + T and T + V achieved significantly greater improvement
in acne than V + V based on mean percentage reduction in noninflammatory lesions
(46% and 41% vs 2%; P = .002) and inflammatory lesions
(38% and 34% vs 9%; P = .01), percentage of treatment
successes (64% and 61% vs 15%; P<.001), and reduction
in overall disease severity (30% and 29% vs 3%; P<.001).
Local adverse effects did not differ significantly among the 3 groups after
week 4.
Conclusion Short-contact 0.1% tazarotene gel therapy is a safe and effective new
method of acne treatment.
INTRODUCTION
ACNE TREATMENT with topical retinoids originated in 1969 with the discovery
by Kligman et al1 of vitamin A acid for this
disorder. Tazarotene, which was introduced in 1997, is the newest retinoid
agent for treating acne and the sole member of this class approved by the
Food and Drug Administration for topical psoriasis therapy.2
It is available in both gel and cream vehicles containing either 0.05% or
0.1% tazarotene, but only the 0.1% formulations are Food and Drug Administration
approved for acne. Tazarotene has also been used successfully for basal cell
carcinoma,3 chronic sun damage,4
and congenital ichthyosis.5
Retinoids as a group exert their effects after activation of 2 families
of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors,
each having alpha, beta, and gamma subclasses.6-9
Whereas tretinoin is a flexible molecule that binds to all RAR subclasses,
tazarotene and adapalene are rigid, receptor-selective retinoids.10-11 Tazarotene is converted in the skin
to its active metabolite tazarotenic acid, which has a high affinity for RAR-beta
and RAR-gamma.12 It does not activate the RAR-alpha
subclass or retinoid X receptors. Retinoic acid receptor–gamma is the
most ubiquitous RAR in mature keratinocytes.13
This subclass has been shown to mediate desirable and adverse retinoid effects
in animal models.14 The mechanisms of action
of tazarotene, most extensively studied in psoriatic skin, are normalization
of keratinocyte proliferation and differentiation as well as reduction in
keratinocyte-expressed markers that attract inflammatory cells.15-17
Local adverse effects, including skin peeling, dryness, redness, burning,
and itching, often limit topical retinoid use.18
During one author's (S.B.) early experience with tazarotene for facial acne,
several patients noted skin discomfort within 10 minutes of application.19 In some cases, typical retinoid-induced skin irritation
occurred, even when tazarotene was removed after such limited exposure. The
possibility of avoiding adverse effects by shortening the period of skin contact
with tazarotene was intriguing. Preliminary exploration suggested that acne
improvement and good tolerability might result from exposure times shorter
than 5 minutes repeated regularly for 12 weeks.19
The goal of this study was to assess acne progress and local skin irritation,
using a novel short-contact method of applying 0.1% tazarotene gel (Tazorac;
Allergan Inc, Irvine, Calif), in patients with mild to moderate facial acne.
Comparisons of these measures were made among 3 groups: those using 0.1% tazarotene
gel twice daily (T + T), those using 0.1% tazarotene gel once daily and nonmedicated
(vehicle) gel once daily (T + V), and a control group using vehicle gel twice
daily (V + V).
PATIENTS AND METHODS
PARTICIPANTS AND SETTING
A total of 99 patients aged 12 to 39 years with facial acne were enrolled
at 2 study sites affiliated with the Department of Dermatology of the Mount
Sinai School of Medicine. Forty patients were enrolled at a suburban office
practice (site 1) and 59 were enrolled at an urban medical center outpatient
facility (site 2). All patients were volunteers recruited via local advertisements
or posters exhibited on site.
Patients were required to understand and follow the study protocol,
which was approved by the medical school institutional review board. Patients
and parents or legal guardians of those younger than 18 years gave written
informed consent. Inclusion criteria required patients to be 12 years or older
and to have mild to moderate facial acne, defined as 10 to 200 noninflammatory
lesions (open and closed comedones), 10 to 60 inflammatory lesions (papules
and pustules), and fewer than 3 nodulocystic lesions. Medication-free periods
were required before study entry as follows: systemic retinoids, 24 months;
oral antibiotics, 4 weeks; and topical acne medications, 2 weeks. Female patients
were permitted to take oral contraceptives if initiated at least 3 months
before study entry and continued throughout the study. Female patients were
excluded if they were pregnant, breastfeeding, or sexually active without
using reliable contraception.
STUDY PROTOCOL
This study was randomized, investigator-masked, and controlled by using
a nonmedicated (vehicle) gel identical to the base of tazarotene gel. The
gels were distributed in identical boxed pairs of 30-g tubes labeled "morning
application" and "evening application." 0.1% tazarotene gel and vehicle gel
are odorless and colorless. Because of possible irritation from tazarotene,
patient blinding was assumed to be potentially compromised. To maintain investigator
masking, clinical assistants collected and recorded data regarding facial
skin signs and symptoms, and physician-investigators assessed efficacy measures.
Patients were randomly assigned to 1 of 3 treatment groups, each having
33 enrollees: (1) patients in the T + T group received 0.1% tazarotene gel
as the morning and evening application; (2) patients in group T + V received
0.1% tazarotene gel as the evening application and vehicle gel as the morning
application; and (3) patients in group V + V received vehicle gel as the morning
and evening application.
All patients received instruction cards detailing the short-contact
method, which required twice-daily (morning and evening) application of the
study gel, spread thinly to facial skin after washing with a nonsoap liquid
cleanser (Cetaphil; Galderma Laboratories, LP, Fort Worth, Tex) and rinsing
with lukewarm water. The dosage of gel per application was approximately 0.6
g, described and demonstrated to patients as a pea-sized amount. Patients
rinsed with lukewarm water after contact periods starting with 2 minutes per
application (timed using digital timers [Big-Digit Timer, RadioShack, Fort
Worth] that were provided to monitor all applications). All patients were
instructed to increase the contact period, if tolerated without local effects,
in 1-minute increments at intervals of at least 3 days to a maximum of 5 minutes.
The written instructions directed patients to reduce the contact period to
30 seconds if peeling, erythema, dryness, burning, or itching occurred. In
such cases, patients were to increase the contact period in 30-second increments
at intervals of at least 3 days, if tolerated, to the 5-minute maximum. Patients
were requested to maintain diary records in which they recorded contact periods
of all applications. Clinical assistants collected these records at each visit.
CLINICAL ASSESSMENTS
Patients were seen at baseline, defined as the visit when treatment
was initiated, and again at 2, 4, 8, and 12 weeks of treatment. At each visit,
physicians used 3 methods to assess efficacy for acne. First, facial lesion
counts were performed of individual acne lesions, divided into noninflammatory
lesions (open and closed comedones), inflammatory lesions (papules and pustules),
and nodules (lesions  4 mm). Second, global response to treatment scores
were assessed by comparing the patient's condition with baseline photographs
and then were graded from 0 to 6 as follows: 0, completely cleared; 1, approximately
90% improved; 2, approximately 75% improved; 3, approximately 50% improved;
4, approximately 25% improved; 5, no change; and 6, exacerbation. Third, overall
disease severity scores were assessed by physical examination and were graded
from 0 to 6 as follows: 0, none; 1, less than mild; 2, mild (slightly noticeable);
3, worse than mild but less than moderate; 4, moderate (evident); 5, worse
than moderate but less than severe; and 6, severe (very distinctive).
At site 1, one physician-investigator (S.B.) made all acne assessments
throughout the 12-week study. At site 2, two physician-investigators (M.-H.T.
and D.W.S.) assessed patients interchangeably. Global response to treatment
scores were aided by high-resolution baseline 20.3 x 25.4-cm glossy
photographs of 3 views per patient.
Nonphysician clinical assistants assessed facial skin signs and symptoms,
including peeling, erythema, dryness, burning, and itching, by interview and
physical examination. At each visit, patients were asked to report the occurrence
and severity of all signs and symptoms that occurred since the previous visit,
even if such signs and symptoms had resolved by the time of the visit. Signs
and symptoms were graded on a scale from 0 to 5 as follows: 0, none; 1, trace
(mild, localized, awareness without discomfort); 2, mild (mild, diffuse, intermittent
discomfort); 3, moderate (moderate, diffuse, continuous discomfort); 4, marked
(moderate, dense, continuous discomfort occasionally interfering with activities);
and 5, severe (prominent, dense, continuous discomfort often interfering with
normal activities).
Laboratory testing was limited to urine pregnancy tests at baseline
and at 12 weeks for all female patients to exclude pregnant women from study
entry and to identify pregnancies that might occur during the study despite
warnings. No positive test results were recorded.
PHOTOGRAPHY
During each visit, front and bilateral 45° side facial views of
every patient were taken using a platform-mounted 35-mm SLR camera system
(Nikon Corp, Tokyo, Japan) with a fixed-magnification 60-mm lens (f2.8) (Nikkor;
Nikon Corp) and a dual-point light system (Twinflash; Canfield Scientific,
Inc, Fairfield, NJ). Patients were positioned in a stereotactic device (Canfield
Scientific, Inc) designed to capture registered serial photographs using standardized
subject angles, framing, lighting, exposure, and reproduction ratio.
STATISTICAL ANALYSIS
Treatment success, one of the primary outcome measures, was based on
achievement of a global response to treatment score of 0 to 3 (50%-100% improvement).
A sample size of 99 patients (33 patients per treatment arm) was required
based on the following assumptions: (1) use of a 2-sided test with 
= .05 and a power of 0.8; (2) an average difference between the active treatment
regimens and the control regimen of 35% (ie, "successes" in the treatment
groups = 50% and successes in the control group = 15%); and (3) a dropout
rate of 15%.
Analyses were conducted on an intent-to-treat basis and included all
patients randomized to the study treatment. The  2 procedure
was used to compare the sex and race of the 3 treatment groups at baseline
and to compare nodule counts. Analysis of variance was used to compare all
other measures, including other baseline characteristics, lesion counts, global
response to treatment scores, overall disease severity scores, and facial
skin sign and symptom scores. Comparisons between active treatment and control
pairs were computed using the Dunnett 2-tailed t
test. In the analyses of all outcome measures, including lesion counts, global
response to treatment scores, overall disease severity scores, and facial
skin signs and symptoms, the last recorded score for each patient was carried
forward to all subsequent visits.
The SAS PLAN procedure computer program (SAS Institute Inc, Cary, NC),
using 3 treatments in blocks of 6, was used to generate treatment allocation
for 102 patients and to obtain randomization. Patients were randomized to
treatment through the sequential allocation of patient numbers at the first
study visit. Sealed opaque envelopes containing treatment allocation information
for each patient number were maintained at a separate location by a contract
research organization (Integrated Research Inc, Dollard-des-Ormeaux, Quebec).
Treatment allocation was not revealed for any study patient efore the completion
of statistical analyses.
RESULTS
PATIENT CHARACTERISTICS
Of 99 patients enrolled, 64 were female and 35 were male. The median
age was 25 years (range, 12-39 years). There were no significant differences
in demographic characteristics among the 3 treatment groups (Table 1).
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Table 1. Comparability of Demographic Data, Acne Characteristics, and
Facial Skin Signs and Symptoms Among Treatment Groups at Baseline
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Eighteen (18%) of 99 patients did not complete the study: 6 in the T
+ T group, 4 in the T + V group, and 8 in the V + V group (Figure 1). The differences in discontinuation rates in the 3 treatment
groups were not significant (P = .44).
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Figure 1. Participant flow and treatment
visits completed.
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Treatment groups demonstrated similar baseline distributions of acne
lesions (open comedones, closed comedones, papules, pustules, and nodules)
and facial skin signs and symptoms (Table
1). The mean overall disease severity score at baseline of the V
+ V group was lower than that of the active treatment groups (P = .05).
ACNE EFFICACY
Reductions from baseline in noninflammatory lesions in the T + T and
T + V groups, expressed as mean ± SD percentage change, were significantly
greater than in the V + V group from week 4 to week 12 (P = .002) (Figure 2). At
week 12, reductions of 46.06% ± 38.31%, 41.19% ± 39.24%, and
2.48% ± 35.84% were observed in the T + T, T + V, and V + V groups,
respectively.
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Figure 2. Mean percentage change in open
and closed comedones. See the "Study Protocol" subsection of the "Patients
and Methods" section for descriptions of the treatment groups.
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At week 12, inflammatory lesions, excluding nodules, were significantly
reduced in the T + T and T + V groups compared with the V + V group, as demonstrated
by the mean ± SD percentage change from baseline in papules and pustules:
38.06% ± 36.22%, 33.58% ± 53.25%, and 8.76% ± 34.59%,
respectively (P = .01) (Figure 3). Nodule counts were insufficient to accommodate statistical
comparison. There were no significant differences between the 2 study sites
in mean percentage reduction in noninflammatory or inflammatory lesions in
any treatment group.
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Figure 3. Mean percentage change in papules
and pustules. See the "Study Protocol" subsection of the "Patients and Methods"
section for descriptions of the treatment groups.
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Achievement of treatment success was defined as global response to treatment
of 0 to 3 (50%-100% improvement) by week 12. Significantly more treatment
successes were observed in the T + T and T + V groups than in the V + V group:
64%, 61%, and 15%, respectively (P<.001).
Of 81 patients completing 12 weeks of treatment, 58 submitted complete
diary records. These data show no evidence of a trend correlating treatment
success with length of drug contact (Table
2). Statistical comparisons of subgroups, based on contact duration,
were precluded by insufficient subgroup size.
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Table 2. Treatment Success by Length of Contact Time per Application
at Last Visit in 81 Patients Completing 12 Weeks of Treatment*
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By week 12, significant reductions from baseline in mean ± SD
overall disease severity scores were observed in the T + T and T + V groups,
30.40% ± 30.96 and 29.09% ± 26.01, respectively, compared with
2.78% ± 17.26 in the V + V group (P<.001)
(Figure 4). Significant differences
in this variable became apparent by week 8 (T + T and T + V vs V + V; P<.001).
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Figure 4. Mean percentage change in overall
disease severity. See the "Study Protocol" subsection of the "Patients and
Methods" section for descriptions of the treatment groups.
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Individuals from the 3 treatment groups demonstrating various global
response to treatment scores are shown in Figure 5, Figure 6, and Figure 7.
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Figure 5. A 16-year-old boy in the group
receiving 0.1% tazarotene gel twice daily shown at baseline (A) and at 12
weeks (B), with a global response to treatment score of 2, indicating approximately
75% global improvement.
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Figure 6. A 13-year-old girl in the group
receiving 0.1% tazarotene gel once daily and vehicle gel once daily shown
at baseline (A) and at 12 weeks (B), with a global response to treatment score
of 1, indicating approximately 90% global improvement.
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Figure 7. A 16-year-old boy in the group
receiving vehicle gel twice daily shown at baseline (A) and at 12 weeks (B),
with a global response to treatment score of 4, indicating approximately 25%
global improvement.
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FACIAL SKIN SIGNS AND SYMPTOMS
The highest mean scores for peeling, erythema, dryness, burning, and
itching were observed in the T + T group at week 2 or week 4; the maximum
mean ± SD scores achieved for these signs and symptoms were 0.76 ±
0.94, 0.67 ± 0.82, 0.85 ± 0.97, 0.42 ± 0.79, and 0.45
± 0.79, respectively. Mean scores of signs and symptoms did not exceed
1.0, or trace level, for any group throughout treatment. Increases in these
signs and symptoms were significantly greater in the T + T group than in the
V + V group at weeks 2 and 4 for peeling and erythema and at week 2 for dryness
and burning.
Transient increases in these signs and symptoms were more prominent
in the T + V group than in the V + V group at weeks 2 and 4 but did not reach
significance. After week 4, the occurrence and severity of these signs and
symptoms in the active treatment groups did not differ significantly from
those in the control group.
No patient discontinued study medication because of adverse events,
but significantly more related adverse events were observed in the T + T and
T + V groups than in the V + V group (P = .002).
Specifically, 1 or more of the signs and symptoms of local skin irritation
was reported by 16 (48%) of 33 patients in the T + T group, 17 (52%) of 33
in the T + V group, and 3 (9%) of 33 in the V + V group.
Local skin irritation tended to be better tolerated by the T + V group
than by the T + T group. Of patients completing therapy and submitting full
diary records, 10 (50%) of 20 T + T patients reduced the contact period to
less than 2 minutes at some time during the study, whereas 1 (4%) of 23 T
+ V patients reduced the contact period to less than 2 minutes.
COMMENT
The benefits achieved by patients in this study compare favorably with
those reported in a large, multicenter study20
of overnight tazarotene therapy for acne. The mean percentage decrease in
noninflammatory lesions after 12 weeks of overnight 0.1% tazarotene gel was
55% (vs 35% in the control group) compared with 46% and 41% (vs 2% in the
control group) for twice-daily and once-daily short-contact therapy, respectively.
Using overnight therapy, the mean percentage decrease in inflammatory lesions
was 42% (vs 30% in the control group), whereas results achieved using the
short-contact method were 38%, 34%, and 9% for the T + T, T + V, and V + V
groups, respectively.
Two differences in study design might account for the relatively better
response of the control group in the overnight study. First, patients in the
overnight study washed with a soap-based cleanser twice daily, whereas our
patients were prohibited from using soap and surfactant-based cleansers on
facial skin throughout the study. Second, prolonged application of vehicle
gel may have an unexplained palliative effect on acne not seen to the same
extent with short-contact use.
Measures of efficacy in the present study showed continuing trends toward
improvement at week 12 (Figure 2, Figure 3, and Figure 4), suggesting that more than 3 months of therapy may be
required to achieve the maximum benefit. Gradual improvement over a several-month
period is the typical acne response to retinoids.20-24
Comparing overnight tazarotene with other topical retinoids, a recent
clinical study21 showed that nightly 0.1% tazarotene
gel is more effective than nightly 0.025% tretinoin gel in the treatment of
comedonal acne. Furthermore, 0.1% tazarotene gel applied every second night
seems to be equivalent therapeutically to 0.1% adapalene gel applied every
night.22
The degree of acne improvement demonstrated in the present study is
similar to that observed in a large multicenter trial23
comparing 0.025% tretinoin gel with 0.1% adapalene gel. Both agents were applied
in the traditional overnight manner. After 12 weeks, the mean percentage reductions
in noninflammatory lesions were 33% and 46% for tretinoin and adapalene, respectively.
Mean inflammatory lesion counts were reduced by 38% in the tretinoin group
and by 48% in the adapalene group. There were significantly fewer incidents
of local skin irritation in the adapalene users than in the tretinoin users,
but more than 30% of the former group and more than 40% of the latter had
erythema and/or scaling of the facial skin persisting at week 12.
Of 446 patients applying tazarotene overnight, 39 (9%) withdrew because
of treatment-related adverse effects, particularly local skin irritation.20 In a 12-week acne study24
comparing 0.1% adapalene solution with 0.025% tretinoin gel, 8 of 149 patients
using adapalene solution and 4 (3%) of 146 patients using tretinoin gel withdrew
because of retinoid-induced effects.
In the present study, signs and symptoms of local skin irritation did
not differ significantly between the once-daily tazarotene group and the control
group at any visit. There were no withdrawals due to treatment-related adverse
effects because the study protocol allowed patients to adjust the contact
period within well-defined limits to avoid such effects. In the previous experience
of Bershad,19 tazarotene sensitivity differed
substantially among individual patients, an observation supported herein.
Data from patients' diary records at week 12 suggest that approximately half
of all patients using active treatment had contact times of 3.5 minutes or
less, whereas the remainder tolerated longer contact periods (Table 2).
A problem inherent in most topical retinoid studies is that noticeable
skin irritation may interfere with investigator blinding. In the present study,
the risk of obvious retinoid dermatitis was virtually eliminated by the patient's
ability to shorten the contact period at the earliest sign or symptom of irritation.
Adverse effects were generally subjective, minor, and transient, mostly occurring
during intervals between visits. In no case was the degree of local skin irritation
so apparent as to be inconsistent with the control regimen.
To our knowledge, this is the first randomized study showing that a
topical retinoid medication can produce pharmacological effects and clinical
improvement after exceedingly short periods of skin contact.
A possible explanation for the efficacy of short-contact therapy may
be found in the percutaneous absorption studies of Rougier and colleagues.25-27 Their work demonstrated
that some topically applied substances achieve a reservoir effect in the stratum
corneum after contact periods as short as 30 minutes.
Percutaneous absorption of tazarotene is a critical issue, as evidenced
by its Food and Drug Administration designation of Pregnancy Category X, prohibiting
its use during pregnancy and breastfeeding. Females of childbearing potential
must use reliable birth control during tazarotene treatment. Although birth
defects have not been reported in humans or laboratory animals after topical
exposure to tazarotene, oral administration of high doses is teratogenic in
animals.28 Another retinoid, isotretinoin,
is well-known to cause birth defects in humans.29
Absorption studies20 in patients with facial
acne using tazarotene gel overnight showed detectable plasma concentrations
of tazarotene ranging from 0.06 to 0.22 ng/mL in 3 patients, and the active
metabolite tazarotenic acid was detected in samples from 4 patients, ranging
from 0.06 to 0.13 ng/mL. These levels are considerably lower than levels of
endogenous retinoids in normal plasma.30
Two of the studies by Rougier and coauthors are particularly relevant
to the issue of systemic absorption. In one study,26
after application of various topical agents to hairless rats, the total doses
absorbed were directly proportional to the duration of application, suggesting
lower systemic levels with shorter contact periods. Another investigation27 found that facial skin, compared with other anatomical
sites, exhibited the most rapid rate of percutaneous absorption, which may
partially offset the theoretical benefit of shorter contact.
Neither the rate of tazarotene absorption into epidermal cells nor the
plasma levels achieved after short-contact therapy have been studied to date,
to our knowledge.28, 31 The dose
absorbed after 5 minutes is likely to be minuscule, since a previous study32 showed that total systemic absorption of tazarotene
was less than 6% of the applied dose after 10 hours under occlusion. If future
investigations confirm that the short-contact method limits tazarotene absorption,
it may have an important safety advantage for premenopausal females.
Another benefit of short-contact therapy is the lack of medication residue
on the skin. Users of short-contact therapy can apply cosmetics, sunblocks,
moisturizers, and other topical preparations without concerns about dilution
or noncompatibility caused by layering of 2 products. This property also facilitates
combination antiacne regimens.
Drawbacks of short-contact therapy are the need for careful timing of
the application and individualized adjustment of the contact period. Some
patients consider overnight therapy simpler for these reasons.
Finally, once-daily short-contact tazarotene therapy offers clear advantages
over the twice-daily regimen. In the present study, the former was about as
effective but less irritating than the latter. Comparing the two, the less
frequent regimen is also more convenient and cost-effective.
AUTHOR INFORMATION
Accepted for publication July 6, 2001.
This study was funded by an unrestricted educational grant from Allergan
Inc, Irvine, Calif, to the Mount Sinai Department of Dermatology (Dr Lebwohl,
Chairman).
This study was presented in part at the American Academy of Dermatology
Summer Meeting, Nashville, Tenn, August 3, 2000.
We thank Betty O'Brien, Natalie Ghosh, and Megan Roddy for their valuable
clinical assistance; Rick Kozloski for his contribution to our study design;
and Andrea Kljajo, MSc, for her help in collecting and analyzing data.
Corresponding author: Susan Bershad, MD, 28 S Mountain Ave, Montclair,
NJ 07042.
From the Department of Dermatology, Mount Sinai School of Medicine,
New York, NY (Drs Bershad, Tan, Sherer, Persaud, and Lebwohl and Ms Kranjac
Singer); and Integrated Research Inc, Dollard-des-Ormeaux, Quebec (Dr Parente).
Dr Bershad holds US patents and reserves all rights to international patents
for the short-contact method of topical retinoid therapy to treat acne, photoaging,
and psoriasis (patents 6017938, 6048902, 6083963, and 6096765). She has received
compensation for speaking engagements from Allergan Inc, Irvine, Calif. Dr
Parente is a co-owner and managing director of Integrated Research Inc, which
has received compensation for clinical research consulting services from Allergan
Inc. Dr Lebwohl has received research grants and compensation for speaking
engagements from Allergan Inc.
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