| Reference | 1. Drugs Today (Barc). 2017 Apr;53(4):239-245. doi: 10.1358/dot.2017.53.4.2604174. <br />
Crisaborole: Phosphodiesterase inhibitor for treatment of atopic dermatitis. <br />
Paton DM(1). <br />
Author information: <br />
(1)University of Auckland School of Medical Sciences, Pharmacology & Clinical
Pharmacology, Auckland, New Zealand. [email protected]. <br />
Atopic dermatitis (AD) is an extremely common condition affecting as many as
10-20% of children and 2-10% of adults. A particularly distressing symptom of AD
is pruritus. One of the important aspects of AD is inflammation associated with
increased activity of phosphodiesterase 4 (PDE4), resulting in decreased
intracellular levels of cyclic adenosine monophosphate, which in turn causes
increased production of inflammatory cytokines. Crisaborole was developed as a
small-molecule, boron-based, selective PDE4 inhibitor that can be used topically.
Clinical trials have demonstrated its efficacy in treating patients with mild to
moderate AD, resulting in significant relief of pruritus. Unlike PDE4 inhibitors
that act systemically, crisaborole does not cause significant gastrointestinal
adverse effects. The most common adverse effect has been temporary stinging and
burning in about 4% of patients upon application of the 2% ointment. To date
there is no evidence of atrophy, telangiectasia or hypopigmentation resulting
from its use. Crisaborole is the first topically applied PDE4 inhibitor to be
approved by the FDA for use in AD. <br />
2. Immunotherapy. 2016 Jul;8(8):853-66. doi: 10.2217/imt-2016-0023. Epub 2016 Jun
10. <br />
Crisaborole and its potential role in treating atopic dermatitis: overview of
early clinical studies. <br />
Zane LT(1), Chanda S(1), Jarnagin K(1), Nelson DB(1), Spelman L(2), Gold LS(3). <br />
Author information: <br />
(1)Anacor Pharmaceuticals, Inc., 1020 East Meadow Circle, Palo Alto, CA, USA.
(2)Veracity Clinical Research, Queensland, Australia.
(3)Henry Ford Health System, Detroit, MI, USA. <br />
Atopic dermatitis (AD), a chronic, relapsing, inflammatory skin disease that is
characterized by intense pruritus and eczematous lesions with up to 90% of
patients presenting with mild to moderate disease. Current topical treatments for
AD have not changed in over 15 years and are associated with safety concerns. In
AD, overactivity of phosphodiesterase 4 (PDE4), leads to inflammation and disease
exacerbation. Crisaborole Topical Ointment, 2%, is a novel, nonsteroidal, topical
anti-inflammatory PDE4 inhibitor currently being investigated for the treatment
of mild to moderate AD. Preliminary studies in children and adults demonstrated
favorable efficacy and safety profiles. Crisaborole may represent an
anti-inflammatory option that safely minimizes the symptoms and severity of AD
and that can be used for both acute and long-term management. <br />
3. J Drugs Dermatol. 2016 Apr;15(4):390-6. <br />
Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory
Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic
Dermatitis. <br />
Jarnagin K, Chanda S, Coronado D, Ciaravino V, Zane LT, Guttman-Yassky E, Lebwohl
MG. <br />
Crisaborole topical ointment, 2% (formerly known as AN2728) is a benzoxaborole,
nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor
investigational compound that recently completed phase 3 studies for the
treatment of mild to moderate atopic dermatitis (AD). The unique configuration of
boron within the crisaborole molecule enables selective targeting and inhibition
of PDE4, an enzyme that converts the intracellular second messenger 3/’5/’-cyclic
adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate
(AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole
controls inflammation. The use of boron chemistry enabled synthesis of a
low-molecular-weight compound (251 daltons), thereby facilitating effective
penetration of crisaborole through human skin. In vitro experiments showed that
crisaborole inhibits cytokine production from peripheral blood mononuclear cells
in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids.
Crisaborole also displayed topical anti-inflammatory activity in a skin
inflammation model. Once crisaborole reaches systemic circulation after topical
application, it is metabolized to inactive metabolites. This limits systemic
exposure to crisaborole and systemic PDE4 inhibition. In phase 1 and 2 clinical
studies, crisaborole ointment, 2% was generally well tolerated and improved AD
disease severity scores, pruritus, and all other AD signs and symptoms. Two
large, randomized, controlled, phase 3, pivotal clinical trials assessing the
efficacy and safety of crisaborole topical ointment, 2% in children, adolescents,
and adults with mild to moderate AD were recently completed with positive
results. <br />
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