<p>Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis</p>

Abstract

Background Atopic dermatitis (AD) is a common chronic, inflammatory skin condition. The pathogenesis of AD involves many cytokines that utilize the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling cascade; therefore, JAK inhibitors may be used in the treatment of AD. This review aims to evaluate the pathophysiology, efficacy, and safety of JAK inhibitors and their emerging role as a therapeutic option for patients with AD. Methods A PubMed search of Phase I, II, and III clinical trials was conducted for relevant literature published between January 2015 and June 2020 utilizing the key terms: JAK inhibitors, atopic dermatitis, efficacy, safety, and treatment. The search was subsequently expanded to include additional terms. Results In multiple Phase II and III clinical trials, JAK inhibitors were more efficacious than placebo or vehicle controls and slightly more efficacious in direct comparisons to corticosteroids. Overall, JAK inhibitors have a moderate safety profile for use in AD. Some of the more severe theoretical adverse events included thrombosis and reactivation of viral infections. While data remain limited for the long-term efficacy and safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results. Discussion Short-term data suggest that both topical and oral JAK inhibitors are efficacious and safe for use in patients with AD, although cases of thrombosis and viral disease have been reported. While the current standard treatments for AD are likely preferred, failed therapy with these agents or corticosteroid phobia may be indications for the use of JAK inhibitors in patients with AD.

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges

“…Further, though it is often well tolerated by patients, mild-to-moderate adverse events have been reported, including headaches, nausea, diarrhea, and mild hypertension. [135][136][137] A phase 2b clinical trial recently completed in mid-2020 evaluated the efficacy, safety, and tolerability of once daily oral gusacitinib in 97 participants with moderate-to-severe chronic hand eczema otherwise refractory to topical therapeutics. 50 Participants were randomized to receive 40mg of gusacitinib, 80mg of gusacitinib, or a placebo tablet for 32 weeks, and symptomatic change from baseline was measured using the mTLSS and PGA (Table 1).…”

Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis: A Post Hoc Analysis of 3 Phase 3 Studies

“…Several other JAK inhibitors that are approved or under investigation (both oral and topical formulations) for the treatment of atopic dermatitis are also being investigated for rapid onset of action for itch [18][19][20][21][22]. While these studies are not head-to-head and do not allow direct comparison of different agents, collectively they suggest that JAK inhibitors are an efficacious therapeutic option with a rapid onset of action in patients with atopic dermatitis.…”

New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression

“…Additionally, JAK-STAT pathways are involved in eosinophil activation, B-cell maturation, up-regulation of epidermal chemokines, and down-regulation of antimicrobial peptides [ 149 , 150 ]. Thus, inhibiting JAKs that regulate multiple steps in AD pathogenesis seems to be conceptually attractive as a treatment option [ 151 , 152 , 153 ].…”