![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Introduction
Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant morbidity and reduced quality of life, especially in patients with moderate–severe AD. Recently, topical and oral Janus kinase (JAK)-inhibitors were investigated as treatments for mild-moderate and moderate–severe AD. However, rare serious adverse-events observed with JAK-inhibitor therapy in AD, rheumatoid arthritis, and other immune-mediated disorders warrant careful consideration.
Areas covered
This review examines the efficacy and safety of topical and oral JAK-inhibitors for treatments in AD, and reviews potential applications in AD.
Expert opinion
JAK-inhibitors have rapid-onset and robust and durable efficacy, which give them considerable versatility for treating the gamut of AD patients. While the U.S. Food and Drug Administration has only approved upadacitinib and abrocitinib to treat moderate–severe AD refractory to treatment with other systemic medications including biologics, or when use of those therapies is not recommended, oral JAK-inhibitors have the potential to be used both as first-line or second-line systemic therapies in moderate–severe AD. However, oral JAK-inhibitors can lead to laboratory anomalies and rare serious adverse events. All of these important characteristics should be addressed in shared-decision-making conversations, patient counseling, choosing appropriate therapies for patients, and monitoring patients in clinical practice.
Article highlights
Abrocitinib and upadacitinib have demonstrated superior efficacy in head-to-head trials with dupilumab.
Long-term adverse event (AE) studies with JAK-inhibitors were performed in tofacitinib, a non-selective pan JAK inhibitor, and in the rheumatoid arthritis patient population, not in patients with atopic dermatitis.
JAK-inhibitor prescribing should be limited in those who may be at high risk of AEs including older age, elevated baseline malignancy risk, and the presence of cardiac risk factors.
Although only FDA approved for the use in moderate–severe AD that is refractory to prior systemic therapy, oral JAK-inhibitors may be considered in patients with moderate–severe AD in the following scenarios: for short or intermediate treatment, for induction treatment followed by an alternative therapy for long-term control, for long-term continuous treatment, or used as a second-line therapy in patients with an inadequate response or AEs leading to discontinuation from prior systemic therapies.
Abbreviations
| AD | = | atopic dermatitis |
| QOL | = | quality of life |
| U.S. | = | United States; |
| TCS | = | topical corticosteroids |
| TCI | = | topical calcineurin inhibitors |
| IL | = | interleukins |
| JAK | = | Janus kinase |
| AEs | = | adverse-events |
| STAT | = | signal transducer and activators of transcription |
| EASI-75 | = | Eczema Area and Severity Index–75 |
| IGA | = | Investigator Global Assessment |
| vIGA | = | validated Investigator Global Assessment |
| RCT | = | randomized clinical trials |
| DBPCRCT | = | double blind placebo-controlled randomized clinical trial; SCORADSCORing AD index |
| PP-NRS | = | Peak Pruritus Numerical Rating Scale |
| IGA-TS | = | Investigator Global Assessment treatment success |
| FDA | = | Food and Drug Administration |
| CDC | = | Centers for Disease Control and Prevention |
| RZV | = | recombinant zoster vaccine |
| NMA | = | network meta-analysis |
| NNT | = | number needed to treat |
| SUCRA | = | surface under the cumulative ranking curve |
| OLE | = | open-label extension |
| hMAb | = | human monoclonal antibody |
| TRuE | = | Topical Ruxolitinib Evaluation in Atopic Dermatitis |
| HRQoL | = | Health-Related Quality of Life |
| HZ | = | herpes zoster |
| mEASI | = | modified Eczema Area and Severity Index |
Declaration of interest
J Silverberg has received honoraria as a consultant and/or advisory board member for Abbvie, Afyx, Aobiome, Arena, Asana, Aslan, BioMX, Biosion, Bluefin, Bodewell, Boehringer-Ingelheim, Cara, Celgene, Connect Biopharma, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Luna, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon; speaker for Abbvie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; data safety monitoring committee member for Afyx, Hoth, Morphosys; institution received grants from Galderma, Pfizer. 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.
Acknowledgement
This manuscript was created based on lectures presented at the 2021 Revolutionizing Atopic Dermatitis (RAD) international, multidisciplinary conference on June 13, 2021.
Reviewer disclosures
One peer reviewer is a consultant, speaker, and investigator for the following: Abbvie, Leo, Pfizer, Eli Lilly. One peer reviewer is a speaker and adviser for the following: Abbvie, Amgen, Janssen, Eli Lilly, Leo, Novartis, Pfizer, Sun Pharma, Ortho Dermatologic, Regeneron/Sanofi, EPI. Peer reviewers in this manuscript have no other relevant financial relationships or otherwise to disclose.