A novel therapeutic paradigm for patients with extensive alopecia areata

ABSTRACT

Introduction: Alopecia areata (AA) is a common, T-cell mediated, hair-centered skin disease that lacks efficacious, long-term therapies for extensive disease. Systemic immune suppressants are usually used, despite their nonspecific actions, often associated with substantial side effects. Although, the Th1 pathway was suggested as pivotal in the disease, recent studies suggest that Th2, Th9, phosphodiesterase (PDE) 4, and IL-23 axes might contribute to AA pathogenesis.

Areas covered: This paper provides an overview of activated immune pathways in AA and possible therapeutic modalities.

Expert opinion: The translational revolution leading to improved therapeutic strategies has just begun for AA. These treatments are often associated with better safety and higher efficacy compared to currently used immune-suppressants. Different pathways might drive the inflammatory process in AA. Ongoing and future clinical trials utilizing narrow- targeted therapeutics will be able to better elucidate the role of each cytokine pathway in creating the AA disease phenotype.

KEYWORDS:

• Alopecia areata
• abatacept
• aldesleukin
• alefacept
• anti-TNF
• apremilast
• dupilumab
• JAK inhibitors
• secukinumab
• tralokinumab
• ustekinumab

Article highlights

• Extensive AA is extremely difficult to treat. Current systemic treatment options mostly show limited efficacy and are often associated with major adverse effects.

• Recently, genetic and translational research has suggested that few cytokine pathways are activated in AA patients, including Th1, Th2, Th9/IL-9, IL-23 and PDE4.

• Therapeutic response biomarkers have been recently identified for AA, allowing better comparison of reversal of hair growth using different therapeutics.

• Various broad and specific treatments are being tested in clinical trials for extensive AA patients. JAK inhibitors and IL-23 antagonists demonstrated impressive clinical responses in small proof-of-concept studies. PDE4 antagonism showed reversal of AA in a mouse AA model.

• Translational studies using narrow-targeted therapeutics may help dissect the contribution of different cytokines to the AA disease phenotype.

This box summarizes key points contained in the article.

Declaration of interests

E Guttman-Yassky has board memberships with Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, Leo Pharma, AnaptysBio, Celsus, Dermira, Galderma, Novartis, Pfizer, and Vitae; has consultant arrangements with Regeneron, Sanofi Aventis, MedImmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, Drais, AbbVie, Anacor, AnaptysBio, Dermira, Galderma, Leo Pharma, Novartis, Pfizer, Vitae, Mitsubishi Tanabe, and Eli Lilly, and has received grants from Regeneron, Celgene, BMS, Janssen, Dermira, Leo Pharma, Merck and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.