vehicle once daily for 12 weeks. As early as week 2, total, inflammatory,
and noninflammatory lesion counts were reduced
in the topical combination arm compared with the vehicle arm.
At week 12, topical combination therapy plus doxycycline was
statistically significantly superior to vehicle plus doxycycline
in reducing total, inflammatory, and non-inflammatory lesion
counts. A rapid reduction in P. acnes in the adapalene/BPO plus
doxycycline group vs the doxycycline alone group—particularly
within the first 4 weeks—was demonstrated through the use
of digital UV fluorescence photography.28
The second portion of this study, which was also double-blind, randomized,
and controlled, enrolled the subjects who had achieved
at least 50% global improvement in the previous 12-week treatment.
Subjects were randomized to receive adapalene/BPO gel or
its vehicle once daily for 24 weeks. At week 24, subjects using adapalene/
BPO had a significantly higher rate of lesion maintenance
success (at least 50% improvement in lesion counts achieved in
initial treatment) for all types of lesions. Fifty-seven percent of
subjects receiving adapalene/BPO had maintained 100% of the effect
at week 24 following discontinuation of oral antibiotics. That
number of subjects was 74% for the 70% of the effect at week 24.
Another open label study by Leyden has demonstrated that
adaplene 0.1%/BPO 2.5% gel was able to reduce effectively skin
colonization by antibiotic sensitive and antibiotic resistant P.
acnes over 4 weeks in healthy volunteers.29
Acne vulgaris has long been known to be an inflammatory
disease rather than an infective one. However, the emerging concept
of subclinical inflammation and its effect on development
and progression of acne lesions correlating with the sequence of
the underlying inflammation process has been a major change
in our understanding of acne pathogenesis. Thus, inflammation
has become the major feature of the disease process from
onset to resolution, including postinflammatory erythema, postinflammatory
hyperpigmentation, and scarring. Therefore, this
new paradigm may even necessitate change of nomenclature,
such as from postinflammatory hyperpigmentation and postinflammatory
erythema to persistent hyperpigmentation and
persistent erythema, since there is no end of inflammation in
this disease process. Additionally, the term “noninflammatory”
lesions should be eliminated, since we now know that all lesions
are of an inflammatory nature, albeit subclinically.
Therefore, our treatment targets may also need to be reconsidered,
with more emphasis on anti-inflammatory treatments.
Dr. Kircik has served as an advisor, investigator, consultant, and
speaker for Galderma, Allergan, Bayer, Promius Pharma, Quinnova,
Stiefel/GSK, LeoPharma, Taro, Valeant, and Warner Chilcott.
Kang S, Cho S, Chung JH, Hammerberg C, Fisher GJ, Voorhees JJ. Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo.
Am J Pathol. 2005;166(6):1691-1699.
Shaheen B, Gonzalez M. A microbial aetiology of acne: what is the evidence?Br J Dermatol. 2011;165(3):474-485.
Kim J. Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses.
Rosen T. The Propionibacterium acnes genome: from the laboratory to the clinic.
J Drugs Dermatol. 2007;6(6):582-586.
Webster GF, Kim J. The immunology of acne. In: Gaspari AA, Tyring SK, eds.
Clinical and Basic Immunology. London: Springer-Verlag; 2008:217-222.
Do TT, Zarkhin S, Orringer JS, et al. Computer-assisted alignment and tracking of acne lesions indicate that most inflammatory lesions arise from comedones and de novo.
J Am Acad Dermatol. 2008;58(4):603-608.
Lee SE, Kim JM, Jeong SK, et al. Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes.
Arch Dermatol Res. 2010;302(10):745-756.
Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ. Inflammatory events are involved in acne lesion initiation.
J Invest Dermatol. 2003;121(1):20-27.
Chronnell CM, Ghali LR, Ali RS, et al. Human beta defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions.
J Invest Dermatol. 2001;117(5):1120-1125.
Trivedi NR, Gilliland KL, Zhao W, Liu W, Thiboutot DM. Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling.
J Invest Dermatol. 2006;126(5):1071-1079.
Del Rosso JQ, Kircik LH. The sequence of inflammation, relevant biomarkers, and the pathogenesis of acne vulgaris: what does recent research show and what does it mean to the clinician?
J Drugs Dermatol. 2013;12(suppl 8):s109-s115.
Fitz-Gibbon S, Tomida S, Chiu BH, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne.
J Invest Dermatol. 2013;133(9):2152-2160.
Lee WJ, Jung HJ, Lim HJ, Jang YH, Lee SJ, Kim DW. Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities.
J Eur Acad Dermatol Venereol. 2013:27(5)643-646.
Mays RM, Gordon RA, Wilson JM, Silapunt S. New antibiotic therapies for acne and rosacea.
Dermatol Ther. 2012;25(1):23-37.
Dreno B, Reynaud A, Moyse D, Habert H, Richet H. Erythromycin-resistance of cutaneous bacterial flora in acne.
Eur J Dermatol. 2001;11(6):549-553.
Eady AE, Cove JH, Layton AM. Is antibiotic resistance in cutaneous propionibacteria clinically relevant? Implications of resistance for acne patients and prescribers.
Am J Clin Dermatol. 2003;4(12):813-831.
Gollnick H1, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne.
J Am Acad Dermatol. 2003;49(suppl 1):s1-s37.
Symphony Health PHAST Monthly Prescription.
Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group.
J Am Acad Dermatol. 2009;60(suppl 5):s1-s50.
Dutil M. Benzoyl peroxide: enhancing antibiotic efficacy in acne management.
Skin Therapy Lett. 2010;15(10):5-7.
Pariser D, Bucko A, Fried R, Jarratt MT, et al. Tretinoin gel microsphere pump 0.04% plus 5% benzoyl peroxide wash for treatment of acne vulgaris: morning/morning regimen is as effective and safe as morning/evening regimen.
J Drugs Dermatol. 2010;9(7):805-813.
Brodell RT, Schlosser BJ, Rafal E, et al. A fixed-dose combination of adapalene 0.1%-BPO 2.5% allows an early and sustained improvement in quality of life and patient treatment satisfaction in severe acne.
J Dermatolog Treat. 2012;23(1):26-34.
Gold LS, Tan J, Cruz-Santana A, et al. A North American study of adapalene-benzoyl peroxide combination gel in the treatment of acne.
Gollnick HP, Draelos Z, Glenn MJ, et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients.
Br J Dermatol. 2009;161(5):1180-1189.
Tan J, Gollnick HP, Loesche C, Ma YM, Gold LS. Synergistic efficacy of adapalene 0.1%-benzoyl peroxide 2.5% in the treatment of 3855 acne vulgaris patients.
J Dermatolog Treat. 2011;22(4):197-205.