Novel investigational drugs for alopecia areata and future perspectives

ABSTRACT

Introduction

Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. While acute, solitary patches often spontaneously remit, developing secondary patches or failure of the disease to resolve within 6-12 months predicts a poor prognosis, with an increased risk of alopecia totalis or universalis. Chronic AA increases the risk of depression and suicidality and reduces quality of life. Treatment options for chronic or acute diffuse AA were previously limited to corticosteroids and traditional immunomodulators. Two Janus Kinase (JAK) inhibitors are now approved for the treatment of chronic AA.

Areas covered

The results of landmark phase 3 trials for three JAK inhibitors, baricitinib, ritlecitinib, and deuruxolitinib are discussed. Evidence for other JAK inhibitors, biologics, and phosphodiesterase-4 inhibitors are also presented. Therapies currently undergoing clinical trials are listed.

Expert opinion

JAK inhibitors are a safe and efficacious treatment of moderate-to-severe AA. Early intervention, regardless of severity, allows for improved treatment efficacy. It is uncertain how long patients should remain on JAK inhibitors; discontinuation often leads to relapse. A black-box warning for JAK inhibitors was extrapolated from safety data in a rheumatoid arthritis cohort; recent meta-analyses of JAK inhibitors used in dermatology cohorts do not demonstrate the same risk profile.

KEYWORDS:

• Alopecia areata
• alopecia treatment
• JAK inhibitors
• baricitinib
• ritlecitinib
• deuruxolitinib
• tofacitinib
• dupilumab
• upadacitinib
• hair

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Article highlights

• The pathogenesis of alopecia areata (AA) involves interferon gamma (IFNγ) mediated loss of hair follicle immune privilege, possibly in response to an anti-viral immune response.

• Phase 3 randomized-control trials (RCTs) have been published for three oral Janus kinase (JAK) inhibitors used to treat AA in adult patients: baricitinib, ritlecitinib, and deuruxolitinib.

• All three trials demonstrated superior efficacy of JAK inhibitors in treating AA compared with placebo. Headache, nasopharyngitis, acne, and upper respiratory tract infections were the most commonly reported side effects.

• Other systemic JAK inhibitors and biologic agents, such as dupilumab, have demonstrated some efficacy in treating AA. Topical JAK inhibitors, interleukin (IL)-17 inhibitors, IL-2 inhibitors, and apremilast do not have robust supporting evidence, and are not recommended.

• Low-dose systemic minoxidil appears to have synergistic effects with JAK inhibitors, improving hair regrowth and potentially decreasing relapses. The evidence for platelet-rich plasma (PRP) therapy in AA is limited.

Declaration of interest

I Chim has been a sub-investigator in clinical trials for AbbVie, Dermaliq Therapeutics, Eli Lilly and Company, Evelo Biosciences, Hope Medicine, Janssen, Kobiolabs, Kymab, Novartis, Pfizer Inc., and Galderma.

R Sinclair is a current AJD Associate Editor and is an Editorial Board Member. R Sinclair reports being the Director and Founder of Samson Clinical Pty Ltd, participates on the pharmaceutical advisory board for Eli Lilly, Pfizer Inc, Leo Pharmaceutical. He is on the speakers bureau for Abbvie, Novartis; and is Principal Investigator in clinical trials for Amgen, Novartis, Arcutis Biotherapeutics, Aerotech, Merck and Co, Celgene, Coherus BioSciences, Jannsen, Regeneron, MedImmune, Glaxo Smith Kline, Samson Clinical, Boehringer Ingelheim, Oncobiologics, Roche, Ascend, Dermira, AstraZeneca, Akesobio, Reistone Biopharma, UCB, Sanofi, Connect, Arena, Sun Pharma, Bristol Myer Squibb and Galderma.

S Eisman has served on the Australian Dermatology Advisory Alopecia Areata Board, Lebrikizumab Advisory Board for Eli Lilly, Dercos Advisory Board (L’Oreal) and has been an investigator in clinical trials/affiliated with AbbVie, Arena Pharmaceutical, Boston Pharmaceuticals, Botanix, Bristol-Myers Squibb, Dermaliq Therapeutics, Dermira, Eli Lilly and Company, Evelo Biosciences, Hope Medicine, Immunic Therapeutics, Janssen, Kobiolabs, Kymab, LEO Pharma, L’Oreal, Nektar Therapeutics, Novartis, Pfizer Inc., Regeneron, Sanofi, Suzhou Connect Biopharmaceuticals, Takeda pharmaceuticals, TEVA pharmaceuticals, Tigermed and Zai Lab. S Eisman is Treasurer and Board Member of the Australian Hair and Wool Research Society (2019 to present).

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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

JAK = janus kinase. TYK = tyrosine kinase. PO = per oral. SALT = severity of alopecia tool. SALT_X = the percentage of patients who achieved an X% reduction from their starting SALT score. BID = twice daily.

Additional information

Funding

This paper was not funded.