Untitled

BEST PRACTICES IN:
Newer Topical Retinoid Therapies for the Treatment of Acne
Acne is the most common skin disorder in the US,
of adapalene 0.3% gel once daily with tazarotene 0.05% affecting approximately 40 to 50 million people.1 cream (Note: tazarotene 0.05% cream is not indicated for Each year, as many as 6 million acne-related office the topical treatment of acne vulgaris) once daily.16 Study visits are made to physicians who treat the disorder.2 participants were instructed to apply adapalene 0.3% gel Although acne is rarely associated with severe morbidity, to one half of the face and tazarotene 0.5% cream to the mortality, or disability, it can lead to physical scarring that other half of the face. Investigator-assessed overall tolera- can affect an individual’s psychological and emotional bility was in favor of adapalene at days 19 and 22, and subject-assessed tolerability was in favor of adapalene atday 5 (P=0.043 for all). Otherwise, the two drugs were Current Thinking Around Acne Therapy
comparable with respect to local cutaneous tolerability.
According to the American Academy of Dermatology’s As with all retinoid products, patients should be in- (AAD) “Guidelines of care for acne vulgaris management,” structed to avoid harsh, drying cleansers, to apply daily published in 2007, topical retinoids should be used as sunscreen, and to protect their face from the cold and first-line therapy in all but the most severe cases of acne, wind. Noncomedogenic moisturizers should be used to Lawrence F. Eichenfield,
Diane M. Thiboutot, MD
which require more aggressive treatment.3 Other effective Professor and Vice Chair
topical therapies for acne cited by the AAD include ben- Chief, Pediatric and
of Dermatology Research
zoyl peroxide and combinations with erythromycin or Adolescent Dermatology
Co-Director, MD/PhD
clindamycin. Topical antibiotics have also been used to Topical retinoids have long been a mainstay of acne thera- Professor of Pediatrics and
treat acne for many years, however, the use of these agents py with demonstrated efficacy against both inflammatory Medicine (Dermatology)
Associate Program
as monotherapy can be associated with the development of and noninflammatory lesions. Formulations in variable Rady Children’s Hospital,
Director, GCRC
concentrations are helpful for tailoring regimens for indi- San Diego
Penn State University
vidual skin types. The most recently approved topical University of California, San
College of Medicine
Topical Retinoids: The Cornerstone of Therapy
retinoid formulation, adapalene 0.3% gel, has been Diego School of Medicine
Hershey, Pennsylvania
Most cases of acne can benefit from treatment with topical demonstrated to be an effective treatment option for acne retinoids, which are considered a cornerstone of therapy for while maintaining a favorable tolerability profile.
both pediatric and adult acne.3,4 Currently, three topical topical retinoids has been the development of next-genera- retinoids/retinoid analogs—adapalene, tazarotene, and tion retinoids that bind selectively to retinoic acid recep- References
tretinoin—are approved for use in the US.
tors. Adapalene—a receptor-selective retinoid analog—is 1. The Burden of Skin Diseases 2005, 2005, the Society for Investigative While the exact mechanism of action of topical effective at treating both comedonal and inflammatory Dermatology and the American Academy of Dermatology Association.
retinoids in the treatment of acne has not been established, acne, shows low irritation potential, and has not been 2. Stern S. Medication and medical service utilization for acne 1995-1998. J Am Acad Dermatol. 2000;43:1042-1048.
it is thought that retinoids improve acne by increasing the shown to cause sensitization or phototoxicity.9,11 In 1996, 3. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vul- turnover of follicular epithelial cells, thus normalizing fol- adapalene 0.1% gel was first approved to treat acne and a garis management. J Am Acad Dermatol. 2007;54:651-663.
licular keratinization and inhibiting the development of cream form followed in 2000. Tazarotene, another next- 4. Krakowski AC, Eichenfield LF. Pediatric acne: Clinical presentations, eval- the precursor acne lesion, the microcomedo. Retinoids also generation topical retinoid, was approved in 2001 for uation, and management. J Drugs Dermatol. 2007;6:589-593.
help to resolve mature comedones. Preclinical data suggest treating acne and psoriasis. Tazarotene normalizes ker- 5. Millikan LE. The rationale for using a topical retinoid for inflammatory acne. Am J Clin Dermatol. 2003;4:75-82.
that retinoids and retinoid analogs may also have anti-in- atinocyte differentiation and reverses keratinocyte prolifer- 6. Gollnick H, Cunliffe W, Berson D, et al., Global Alliance to Improve Out- flammatory effects. Clinical data confirm that retinoids ation. It is efficacious as monotherapy and is commonly comes in Acne. Management of acne: A report from a Global Alliance to and retinoid analogs significantly reduce inflammatory le- used in combination with a topical antibacterial in pa- Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49(suppl):S1-S37.
sions.5,6,7 (Figure) In addition, the application of a topical
7. Pariser DM, Thiboutot DM, Clark SD, Jones TM, Liu Y, Graeber M, for retinoid may enhance the penetration of other medica- The most recent retinoid analog product to be approved the Adapalene Study Group. The efficacy and safety of adapalene gel 0.3%in the treatment of acne vulgaris: A randomized, multicenter, investiga- tions, such as topical antibiotics and benzoyl peroxide.8 to treat acne is adapalene 0.3% gel, which received ap- tor-blinded, controlled comparison study versus adapalene gel 0.1% and proval in 2007. A phase III, randomized, multicenter, vehicle. Cutis. 2005;76:145-151.
double-blinded clinical trial that compared the safety and 8. Dreno B. Topical antibacterial therapy for acne vulgaris. Drugs. 2004;64: Figure. Topical Retinoids Reduce Facial Lesions
efficacy of adapalene 0.3% gel with adapalene 0.1% gel, 9. Leyden JJ. Topical treatment of acne vulgaris: Retinoids and cutaneous ir- and with vehicle, found that the median lesion count re- ritation. J Am Acad Dermatol. 1998;38:S1-S4. duction was better for the adapalene 0.3% gel than for the 10. Quigley JW, Bucks DA. Reduced skin irritation with tretinoin containing adapalene 0.1% and vehicle gels.13 At week 12, General- polyolprepolymer-2, a new topical tretinoin delivery system: A summary of ized Estimating Equation (GEE) analysis showed a statisti- preclinical and clinical investigations. J Am Acad Dermatol. 1998;38:5-10.
cally significant difference between the adapalene 0.3% 11. Bershad S. Developments in topical retinoid therapy for acne. Semin Cutan and 0.1% groups in the percent reduction in total lesion counts (P=0.020) and inflammatory lesion counts 12. Guenther LC. Optimizing treatment with topical tazarotene. Am J Clin (P=0.015). The pivotal phase II trial of adapalene 0.3% 13. Thiboutot D, Pariser DM, Egan N, et al, on behalf of the Adapalene gel demonstrated that for more challenging acne (higher Study Group. Adapalene gel 0.3% for the treatment of acne vulgaris: A lesion counts with more inflammatory lesions), adapalene multicenter, randomized, double-blind, controlled, phase III trial. J Am gel 0.3% was superior to adapalene gel 0.1% and vehicle Acad Dermatol. 2006;54:242-250.
gel in reducing total inflammatory and noninflammatory 14. Brand B, Gilbert R, Baker MD, et al. Cumulative irritancy potential of adapalene cream 0.1% compared with adapalene gel 0.1% and severaltretinoin formulations. Cutis. 2003;72:455-458. Facial lesions before and after 12 weeks of
treatment with adapalene gel 0.3%.
Tolerability of Topical Retinoids
15. Greenspan A, Loesche C, Vendetti N, et al. Cumulative irritation compar- ison of adapalene gel and solution with 2 tazarotene gels and 3 tretinoin Studies have investigated the cumulative irritancy poten- formulations. Cutis. 2003;72:76-81. Reprinted with permission from Cutis. 2005;76:145-151. tial of different topical retinoid molecules in a number of 16. Dosik JS, Arsonnaud S. Tolerability comparison of adapalene gel, 0.3% formulations. Adapalene 0.1% cream and gel formula- versus tarzarotene cream, 0.05% in subjects with healthy skin. J Drugs tions, as well as solution, have been shown to have signifi- Evolution of Topical Retinoids
cantly less irritation potential than various formulations of Tretinoin was the first topical retinoid to be approved for This supplement was produced by the customized publication department of Elsevier/I use in the US in 1971. It was initially formulated in a In clinical studies, the most typical adverse events asso- NTERNATIONAL MEDICAL NEWS GROUP. Neither the editor of SKIN & ALLERGY NEWS, the Editorial Advisory Board, nor the reporting staff contributed to its penetrating hydroalcoholic vehicle containing a high con- ciated with the use of retinoids include erythema, dry content. The opinions expressed in this supplement are those of the faculty and do centration of active ingredient, but caused many patients skin, pruritus, irritation, and stinging/burning. Similar to not necessarily reflect the views of the sponsor or of the Publisher.
to develop skin irritation. Subsequently, tretinoin cream other retinoids, adverse events associated with use of ada- Copyright 2008 Elsevier Inc. All rights reserved. No part of this publication maybe reproduced or transmitted in any form, by any means, without prior written and gel vehicles in a variety of concentrations became palene gel 0.3% are primarily local cutaneous irritation.
available and improved the irritation side effects, although However, results from clinical studies comparing adapa- Elsevier Inc. will not assume responsibility for damages, loss, or claims of any kind it remained a problem for some patients. Newer topical lene gel 0.3% to adapalene gel 0.1% confirm that adapa- arising from or related to the information contained in this publication, includingany claims related to the products, drugs, or services mentioned herein. The delivery systems—the microsphere and the polyolprepoly- lene gel 0.3% retains a similar safety profile to the less- opinions expressed in this supplement do not necessarily reflect the views of the mer-2 vehicle—have since been developed to deliver the active tretinoin while minimizing irritation.9,10 More recently, Dosik and Arsonnaud conducted a 3- Editorial support provided by Susan Bowes and Medisys Health Communications.
Another means of reducing the irritation potential of week study that compared the local cutaneous tolerability A Supplement to Skin & Allergy News®. This supplement was funded by
www.skinandallergynews.com/content/bestpractices

Source: http://www.skinandallergynews.com/fileadmin/content_pdf/supplement_pdf/t0mpg621_bp_supplement2.pdf