Sanjay Bhambri DO, James Q. Del RossoDO, Avani Bhambri MD
Acne vulgaris is the most common disorder seen in ambulatory dermatology practice. Acne causes signifi cant morbidity and the
direct costs associated with it exceed $2.2 billion per year in the United States (U.S.). The pathogenesis is multifactorial, and our
understanding of the mechanisms involved in the development of acne lesions has improved with time. Follicular hyperkeratinization,
sebum production, presence of Propionibacterium acnes (P. acnes), infl ammatory mediators, and androgens have been identifi ed as
key components of acne pathophysiology. Recent advances have been made in this area with the discovery of P. acnes interaction
with Toll-like receptors (TLRs), vaccines targeting P. acnes or its components, antimicrobial peptides and the role of hormones.
Combination therapy has become the standard for the management of acne, particularly for moderate-to-severe cases. Among these
combinations, those regimens containing benzoyl peroxide (BPO), clindamycin and a retinoid have been used frequently as they address
most aspects of acne pathogenesis. This study compares the effi cacy and safety of two common topical treatment regimens
in the treatment of a moderate to severe facial acne vulgaris: fi xed-combination gel containing BPO 5% and clindamycin 1% (BPO/C)
plus tretinoin microsphere gel 0.04% (RAM) versus a regimen of a fi xed-combination gel containing clindamycin phosphate 1.2%
and tretinoin 0.025% (CPT) plus a once-daily BPO 5% wash. While both regimens were safe and effective, regimen BPO/C+RAM
yielded a more rapid onset of effect versus regimen CPT+BPO against both non-infl ammatory and infl ammatory lesions. Both treatment
regimens were well-tolerated.
Daniel Bucks PhD, Pramod Sarpotdar PhD,Karen Yu PhD, Arturo Angel BS,James Del Rosso DO
Fixed combination products of clindamycin 1% (as 1.2% clindamycin phosphate) and benzoyl peroxide (BPO) 5% are commonly used
in the treatment of acne vulgaris. Although any given topical acne product may be therapeutically effective, signs and symptoms of
cutaneous tolerability may lead to missed applications by the patient, thus limiting adherence to therapy. BPO and other formulation
components such as surfactants, preservatives and high levels of organic solvents can cause cutaneous irritation and dryness. BPO
irritation is dose-dependent. An approach to optimizing the BPO concentration was undertaken to develop a surfactant- and preservative-
free, clindamycin and low concentration (<5%) BPO formulation. A 33% reduction in skin irritation was seen when the BPO
concentration was halved from 5% to 2.5% (clindamycin-BPO 2.5% gel), maintaining a comparable amount of total BPO delivered
to the skin. As a result, clindamycin-BPO 2.5% gel appears to provide effi cacy comparable to that of higher concentration (5%) fi xed
clindamycin-BPO combination products and should optimize patient compliance as a result of the reduction in cutaneous tolerability
reactions, including signs of skin irritation or dryness. Clinical studies have shown clindamycin-BPO 2.5% gel to be highly effective
with the potential for a more favorable tolerability profi le compared to products containing higher concentrations of BPO.
Diane M. Thiboutot MD, Alan B. FleischerMD, James Q. Del Rosso DO,Phoebe Rich MD
This two-phase, multicenter study was undertaken to examine the safety and effi cacy of combination therapy with oral doxycycline
and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent
maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172)
received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for ≤ 12 weeks. In the second, double-blind study
phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved ≥75% infl ammatory
lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24
weeks. Assessments of effi cacy were obtained at four-week intervals throughout both phases of the study and included change
in infl ammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and
telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement,
with the participant rating cosmetic acceptability and the investigator rating treatment as “success” or “failure” based on IGA score.
During the second phase of the trial, the rate of relapse—defi ned as either a 50% deterioration in the lesion count improvement from
phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the
subject—was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events
(AEs) and a rating of cutaneous tolerability by the subject.
By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in infl ammatory lesion
count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently
provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month
duration of the maintenance phase. Additionally AzA 15% gel showed a statistically signifi cantly lower deterioration in absolute
infl ammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs
were encountered in the study, and 98.5% of subjects were satisfi ed with the local tolerability of both AzA gel and vehicle.
This 12-week, single-center, investigator-blinded, randomized, parallel-design study assessed the safety and effi cacy of tretinoin microsphere
gel 0.04% delivered by pump (TMG PUMP) to tazarotene cream 0.05% (TAZ) in mild-to-moderate facial acne vulgaris. Effi cacy
measurements included investigator global assessment (IGA), lesion counts, and subject self-assessment of acne signs and symptoms.
Effi cacy was generally comparable between treatment groups, although TMG PUMP provided more rapid results in several parameters.
IGA showed a more rapid mean change from baseline at week 4 in the TMG PUMP group (-0.18 versus -0.05 in the TAZ subjects). TMG
PUMP yielded more rapid improvement in papules. At week 4, the mean percentage change from baseline in open comedones was
statistically signifi cant at -64% in the TMG PUMP group (P=0.0039, within group) versus -19% in the TAZ group (not statistically signifi -
cant within the group; P=0.1875). Skin dryness, peeling and pruritus were signifi cantly less in the TMG PUMP group as early as week 4.
Adverse events related to study treatment were rare in both groups and all resolved upon discontinuation of study medication.
Tarek Fakhouri BS, Brad A. Yentzer MD, Steven R. Feldman MD PhD
Background: Antibiotic resistance of Propionibacterium acnes (P. acnes) is a growing phenomenon in the wake of widespread use of
topical and systemic antibiotics for acne vulgaris. Benzoyl peroxide has a proven track record of safety and effi cacy, and can decrease
reliance on antibiotics in the treatment of acne.
Purpose: To review the literature for methods to increase the effi cacy and tolerability of benzoyl peroxide (BPO).
Methods: A PubMed literature search was done using the terms “benzoyl peroxide,” “vehicle,” “mechanism,” and “delivery system.”
Relevant papers were reviewed for methods of increasing BPO effi cacy and tolerability.
Results: BPO in concentrations of 2.5%, 5% and 10% are equally effective at treating infl ammatory acne. However, higher concentrations
are associated with more adverse effects. The effi cacy of BPO may be enhanced by the presence of Vitamin E and tertiary
amines. BPO is also more effi cacious if used in combination with topical retinoids than as a monotherapy. Novel vehicles including a
microparticle delivery system and those with a hydrophase or urea base increase the tolerability of BPO without sacrifi cing effi cacy.
Conclusion: Benzoyl peroxide has a proven track record of safety and effi cacy for the treatment of acne. Recent discoveries have
provided new methods of increasing the effi cacy and tolerability of topical BPO, making it useful as monotherapy for mild acne or as
an adjunct in the treatment of moderate to severe acne vulgaris.
James Q. Del Rosso DO FAOCD
Anti-infl ammatory dose doxycycline (ADD), which is the administration of doxycycline 40 mg extended-release capsule once daily, is
the only oral therapy approved by the United States Food and Drug Administration (FDA) for treatment of rosacea. ADD once daily
has been shown to exhibit anti-infl ammatory activity while not demonstrating evidence of antibiotic effects, including with chronic
administration. This article summarizes the clinical studies to date on the use of ADD once daily in papulopustular rosacea, including
both monotherapy and combination therapy studies. The combination therapy approach of ADD once daily and metronidazole gel 1%
once daily has been shown to exhibit a more rapid onset of therapeutic effect than topical therapy alone. ADD once daily has been
demonstrated to be effective in adult subjects with moderate to severe rosacea, and exhibits a favorable safety profi le coupled with
absence of antibiotic selection pressure. Additionally, a much lower incidence of gastrointestinal side effects has been noted with
ADD once daily as compared to doxycycline 100 mg once daily.
No abstract details for the moment.
No abstract details for the moment.
No abstract details for the moment.