Abstract
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use. The pathogenesis of AA is not yet fully understood, but recent investigations of the immune activation in AA skin reveal Th1/IFN-γ, as well as Th2, PDE4, IL-23, and IL-9 upregulations. Tissue analyses of both animal models and human lesions following broad-acting and cytokine-specific therapeutics (such as JAK inhibitors and ustekinumab, respectively) provide another opportunity for important insights into the pathogenesis of AA. As reviewed in this paper, numerous novel therapeutics are undergoing clinical trials for AA, emphasizing the potential transformation of the clinical practice of AA, which is currently lacking. Dermatologists are already familiar with the revolution in disease management of psoriasis, stemming from better understanding of immune dysregulations, and atopic dermatitis will soon follow a similar path. In light of these recent developments, the therapeutic arena of AA treatments is finally getting more exciting. AA will join the lengthening list of dermatologic diseases with mechanism-targeted drugs, thus changing the face of AA.
Highlights
Alopecia areata (AA) is a prevalent autoimmune disease causing loss of hair, with approximately 2% of the population suffering from the condition during their lifetime, most commonly starting before the age of 30 years [1, 2]
We systemically review novel AA therapeutics, by searching PubMed, ClinicalTrials.gov, Google Scholar, and Science Direct using the words ‘‘alopecia areata’’, ‘‘alopecia totalis’’, ‘‘alopecia universalis’’, and ‘‘extensive alopecia’’, with ‘‘treatment’’, ‘‘systemic treatment’’, ‘‘drugs’’, or with specific relevant therapeutics or immune markers such as
We review treatment options that may be beneficial for future clinical trials in AA patients (Table 1; Fig. 1)
Summary
Alopecia areata (AA) is a prevalent autoimmune disease causing loss of hair, with approximately 2% of the population suffering from the condition during their lifetime, most commonly starting before the age of 30 years [1, 2]. JAK inhibitors represent a promising treatment strategy, and the role and safety of various JAK antagonists in the treatment paradigm of extensive AA will be elucidated by large, placebo-controlled clinical trials Another oral small molecule inhibiting broad T cell activation is apremilast—a PDE4 inhibitor. In a three-patients trial of extensive AA of individuals successfully treated with IL-23 inhibitor, PDE genes were significantly upregulated at baseline and downregulated following hair regrowth in all patients [15] These data support a possible role for apremilast in the treatment of extensive AA, as well as potentially for topical PDE4 inhibition for AA patients with limited disease. An ongoing open-label single arm clinical trial will further elucidate the therapeutic potential of abatacept for AA (NCT02018042)
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