Abrocitinib for the treatment of atopic dermatitis

ABSTRACT

Introduction

Janus kinase (JAK) inhibitors are emerging treatments in dermatology. Also known as JAKinibs, these agents target JAK-signal transducers and activators of transcription (JAK-STAT) pathway for intracellular signaling. Among the various immune-mediated inflammatory skin diseases that the JAK-STAT pathway plays a role in, atopic dermatitis (AD) is an important one. AD has a complex and multifactorial pathophysiology that is not fully understood. Immune dysregulation can result in epidermal barrier disruption and intensify atopic dermatitis. The newly developed abrocitinib (PF-04965842) selectively inhibits the JAK1 protein, which is believed to modulate cytokines involved in AD pathophysiology.

Areas covered

This work is a review of the current literature related to abrocitinib, including the phase I, II, and III clinical trials, for the treatment of AD. Immunological considerations of abrocitinib and JAK inhibition are also explored.

Expert opinion

Abrocitinib is among the first JAK inhibitors evaluated for the treatment of AD. Similar to other JAKinhibs that mechanistically block the signaling of several cytokines, abrocitinib possesses both positive and negative clinical attributes. Nonetheless, the risk-benefit profile of abrocitinib remains favorable. Up to 61% of AD patients achieve an EASI 75 response while a minority of responding patients experience mild to moderate symptoms related to tolerability.

KEYWORDS:

• PF-04965842
• abrocitinib
• atopic dermatitis
• eczema
• JAK1
• JAK-STAT Pathway

Article highlights

• The emerging JAK1 inhibitor, abrocitinib, is a prospective atopic dermatitis treatment option

• Abrocitinib mechanistically blocks the signaling of several cytokines involved in atopic dermatitis

• Abrocitinib clinical trials have shown an acceptable efficacy, safety, and tolerability profile that is still evolving

• The clinical trials show improved clinical scores and the atopic dermatitis pruritus symptom

• Further research into atopic dermatitis pathophysiology and the action of abrocitinib will be advantageous for treatment validation.

Declaration of interest

MJ Gooderham has been an investigator, speaker, consultant or advisory board member for AbbVie, Amgen, Akros, Arcutis, Boehring Ingelheim, BMS, Celgene, Dermira, Dermavant, Galderma, GSK, Eli Lilly, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, UCB, Valeant/Bausch. K Papp has been an investigator, speaker, consultant or advisory board member for AbbVie, Amgen, Akros, Arcutis, Boehring Ingelheim, BMS, Celgene, Dermira, Dermavant, Galderma, GSK, Eli Lilly, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sandoz, Sun Pharma, Takeda, UCB, Valeant/Bausch. 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.

Reviewer disclosures

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

Author contributions

All authors have contributed to the preparation of this review and meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship.

Additional information

Funding

This paper was not funded