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FA L L C L I N I C A L D E R M AT O L O G Y C O N F E R E N C E P R O C E E D I N G S FALL CLINICAL DERMATOLOGY 2007 AN UPDATE ON ADVANCES IN ACNE AND EXCERPTS FROM WHAT’S NEW IN THE MEDICINE CABINET BY JAMES Q. DEL ROSSO, D.O., F.A.O.C.D. DERMATOLOGY RESIDENCY DIRECTOR VALLEY HOSPITAL MEDICAL CENTER LAS VEGAS, NV Acne vulgaris is one of the most common diagnoses e n c o u n t e red in clinical practice. Most advances relate to i m p rovements in vehicle technology and new data, especially on combination therapy. C O M B I N ATION TO P I C A L T H E R A P Y Topical retinoids are a vital component of both initial tre a t- James Q. Del Rosso, D.O., F.A.O.C.D. ACNE UPDATE ment and maintenance therapy for acne vulgaris. They exhibit the ability to reduce both non-inflammatory lesions and inflammatory acne lesions. Benzoyl peroxide also remains a foundation of acne treatment, exhibiting the ability to markedly reduce P ropionibacterium acnes c o u n t s and prevent emergence of P. acnes strains that are less sensitive to antibiotics, such as erythromycin and tetracycline. Benzoyl peroxide, including formulations that also contain clindamycin, is well established for reducing inflammatory acne lesions but also for decreasing non-inflammatory lesions by approximately 25% to 30% in clinical trials. Multiple clinical trials have evaluated tretinoin (Retin-A M i c ro, Tretin-X, Atralin), adapalene (Differin), and tazaro t e n e ( Tazorac), including initial pivotal monotherapy studies and trials utilizing combination therapy with a benzoyl pero x i d e (BPO)-containing formulation. The availability of newer vehicles that decrease the potential for and the intensity of initial skin irritation observed with topical retinoid therapy (“re t i n o i d dermatitis”), such as tretinoin formulated in the micro s p h e re gel (Retin-A Micro) and the aqueous-based gel (Atralin), has allowed for effective combination topical therapy of acne vulgaris from the outset. With these newer vehicles, more patients are able to tolerate combination topical tre a t m e n t with few or no signs of skin irritation. B E N Z O Y L PEROXIDE/CLINDAMYCIN + TO P I C A L RETINOID T H E R A P Y Clinical studies have evaluated BPO-clindamycin gel (Duac) used in combination with either tazarotene cream 0.1% (Ta z o r a c ) , t retinoin micro s p h e re gel 0.04% or 0.1% (Retin-A Micro), or adapalene gel 0.1% (Differin). The BPO-clindamycin gel and the topical retinoid were applied in the morning and at bedtime, re s p e c- t i v e l y, in all of the studies. The combination topical approach of a retinoid used along with BPO-clindamycin from the outset of therapy exhibited inflammatory and non-inflammatory lesion re d u c- NEWER VEHICLES T H AT D E C R E A S E THE POTENTIAL FOR AND THE I N T E N S I T Y OF INITIAL SKIN IRRITAT I O N O B S E RVED WITH TO P I C A L R E T I N O I D T H E R A P Y H AVE ALLOWED FOR EFFECTIVE COMBINATION TO P I C A L T H E R A P Y OF ACNE VULGARIS. tions after 12 weeks of at least 60% and 55%, re s p e c t i v e l y, with all 3 retinoids (F i g u res 1–4). In one of the trials, the study arm using both BPO-clindamycin gel (Duac) and tazarotene 0.1% c ream (Tazorac) demonstrated a marked reduction in non-inflammatory lesions at Week 4 (34%) and Week 8 (64%) (F i g u re 3) . Tolerability results were very favorable in all 3 trials. A case re p o r t series of BPO micro s p h e re cream (NeoBenz Micro) applied once daily in the morning used in combination with tretinoin micro s- p h e re gel 0.04% (Retin-A Micro) once daily at night also proved to exhibit effective results with no reports of skin irritation. PROPER SKIN CARE IN ACNE T H E R A P Y The use of appropriate skin care is vital in the management of acne vulgaris, allowing for preservation of epidermal barrier integrity and function. The use of a gentle facial cleanser and S U P P L E M E N T T O S K I N & A G I N G • M A R C H 2 0 0 8 • 3
FA L L C L I N I C A L D E R M AT O L O G Y C O N F E R E N C E P R O C E E D I N G S well-formulated moisturizer both reduces the potential for skin irritation associated with topical medications and enhances the ability of acne medications to reduce lesions. A pre p a c k a g e d kit is available that contains tretinoin cream, a gentle cleanser and a moisturizer (Tretin-X), thus providing an additional “convenience value.” A recent study evaluating the use of t a z a rotene 0.1% cream (Tazorac) and a ceramide-based moisturizer cream (CeraVe Cream) in subjects with acne vulgaris demonstrated that application of the moisturizer first did not i n t e r f e re with therapeutic results and mitigated signs and symptoms of skin irritation. NEWER TO P I C A L RETINOID FORMULAT I O N S Newer topical retinoid formulations that have emerged add to the dermatology armamentarium. Adapalene gel 0.3% ( D i fferin 0.3%) once daily has been shown to produce twot h i rds of its therapeutic effect within the first month of tre a t- ment. A water-based gel containing tretinoin 0.05% (Atralin) applied once daily proved to be comparable to, but not noninferior to, tretinoin micro s p h e re gel 0.1% (Retin-A Micro) based on data from a 12-week controlled study; however, tolerability was superior with the aqueous-based gel. A combination aqueous polymer gel containing clindamycin phosphate 1.2% and tretinoin 0.025% (Ziana) includes tretinoin in both solubilized and crystalline forms. The crystalline form of tretinoin allows for slow release of active drug with very low skin irritation, and particle size is tightly controlled, thus providing optimal penetration. The superior efficacy of the combination clindamycin/tretinoin gel applied once daily as compared to individual active components was established in large, Phase III trials in subjects with mild, moderate, and severe acne vulgaris (Figure 5). NEWER BENZOYL PEROXIDE FORMULAT I O N S Newer formulations of BPO appear to offer the advantages of reduced skin irritation without loss of efficacy and potential- 4 • M A R C H 2 0 0 8 • S U P P L E M E N T T O S K I N & A G I N G
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