Janus kinase inhibitors for the therapy of atopic dermatitis

Abstract

The JAK-STAT pathway is involved in the signaling of multiple cytokines driving cutaneous inflammation in atopic dermatitis (AD). Janus kinase (JAK) inhibitors target individual receptor-associated kinases, thereby preventing the mediation of inflammatory signals. Several JAK inhibitors with varying mechanism of action, potency, and safety represent potential therapeutic options for AD in both topical and systemic application. The JAK1/2 selective JAK inhibitor baricitinib was the first substance from this class of drugs approved by the EMA for the systemic oral treatment of AD. The clinical development program of the JAK1 selective inhibitors upadacitinib and abrocitinib is finalized with positive results for AD. The PAN-JAK inhibitor delgocitinib was the first substance being approved for the treatment of AD (in Japan). This review article covers the rising data on investigational and approved JAK inhibitors in the context of the treatment of AD.

Once-Daily Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults and Adolescents Aged 12 Years and Over: A Short Review of Current Clinical Perspectives

“…JADE COMPARE, a phase 3 placebo-controlled trial, which included adults suffering from moderate-to-severe forms of AD and who received doses of 200 mg or 100 mg of oral abrocitinib daily, is one of the studies, which rendered abrocitinib useful for the systemic treatment of AD. 28 , 31–33 The safety profile of this small molecule with selective anti-JAK1 properties, abrocitinib, was found to be similar to that reported by other studies, demonstrating a fast improvement in the patient’s signs and symptoms. This clinical study had a background in topical treatment (low or medium potency corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors) that was applied to the active lesions, continuing for 7 days after they were under control.…”

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

“…For example, JAK1 is shared by signaling pathways induced by IL-4, TLSP, IL-13, IL-22 and IFN-γ, whereas TYK2 is common to IL-13 and IL-22 signaling. Based on these molecular features, most of JAK inhibitors synergistically act as inhibitors of both the inflammatory responses and pruritus [ 127 ].…”

Healthcare Resource Utilization and Direct Cost of Patients with Atopic Dermatitis in Dubai, United Arab Emirates: A Retrospective Cohort Study

“…Management of AD begins with topical corticosteroids (TCS) followed by topical calcineurin inhibitor (TCI) such as pimecrolimus and tacrolimus, followed by later lines of therapy such as topical therapy of phosphodiesterase 4 inhibitor (crisaborole 2% ointment), systemic immunosuppressants, antimicrobials, phototherapy, and allergen-specific immunotherapy [ 3 , 11 , 12 ]. Recent approved additions to treatment management of AD includes biologics (such as dupilumab, tralokinumab) and JAK inhibitor (such as ruxolitinib, upadacitinib, abrocitinib) [ 13 – 17 ]. The first biologic for AD treatment, dupilumab, was approved in 2017 [ 18 ].…”