An Open-label, Single-arm Pilot Study of the Safety and Efficacy of an Oral PDE4-inhibitor Agent, Apremilast, in the Treatment of Moderate to Severe Acne
The hypothesized sequence of events in inflammatory acne starts with the formation of a
microcomedone with accumulation of cornified keratinocytes within the follicle. Presence
and/or proliferation of P.acnes induces the production of IL-1 alpha, tumor necrosis factor
(TNF)- alpha, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Inflammation caused by CD4+ T cells causes a T-helper 1 cytokine response mediated by
Toll-like receptors (TLR)-2 and TLR-4 whose expression is increased by P. acnes.
Infiltration by neutrophils appears 72 hrs after, with possible disruption of the
follicular wall and more inflammation. TNF-alpha liberated by keratinocytes stimulates the
activation of pro-matrix metalloproteinase (MMP)-2 activity in the dermis with remodeling by
fibroblasts with the consequence of possible scarring.
The usual treatment for moderate to severe inflammatory acne involves the use of long-term
topical retinoids and antibiotics such as doxycycline or minocycline that had been showed to
decrease the inflammatory response as well as decreasing the population of P. acnes. Since
acne is a long term condition, several years of antibiotics are usually required. Recently,
the problematic of antibiotic overuse has received great attention and concerns. Chronic
antibiotic use has been implicated in increasing the risk of breast cancer and upper
respiratory infections, and there is also a concern for antibiotic resistance. Recent
recommendations by the Global Alliance to Improve Outcomes in Acne Group include the
limitation for the use of oral antibiotics to a maximum of 3 months. So there is a need to
find alternatives that does not include the use of oral antibiotics.
The only effective and available treatment for severe acne is isotretinoin which may have
potential serious side effects. Lately also it has been implicated in the development of
depression and suicidal ideations in the teenager population.
A novel anti-inflammatory, not antibiotic drug may be an excellent alternative for the
treatment of moderate to severe acne. Apremilast has been shown to inhibit the production of
tumor necrosis factor (TNF)-alpha, IL-8 and neutrophil infiltration, all of which are
elevated in inflammatory acne. Preliminary data of the use of Apremilast in psoriasis
makes us believe that this medication is safe for short-term use in acne patients.
Our intention is to study Apremilast in the treatment of moderate to severe acne.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of Patients With a Success Rate (Based on the Researcher's Global Assessment (RGA) Sum of Clear (0) or Almost Clear (1))
RGA measures the severity of acne. The scale goes from 0-4. 0 will be better and 4 will be worse. Scores can only be whole numbers (0,1,2,3,4)ordinal.
Aida Lugo-Somolinos, MD
UNC Chapel Hill
United States: Food and Drug Administration
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