Eczema is an inflammatory skin disease that results in a rash and itching. This impacts a patients quality of life including depression, sleep disturbances and even suicidal ideation. Treatments include, moisturizers, topical steroids and calineurin inhibitiors. Despite treatment, many patients still suffer. Advances in recent years have brought new medications, Dupilumab and Eucrisa. Although they have given great benefit to many patients, there still are patients who do not respond to these medications.
Atopic dermatitis is a multifactorial disorder that has various subtypes, there isn’t a “one size fits all” treatment. Dupixent targets IL-4/IL-13, new treatments are on the horizon that can target other cytokines that can play a role in eczema. Below we will discuss some new medications that are being studied.
Nemolizumab, an IL-31 antibody, targets the “itch” cytokine. Studies are ongoing to see if this can alleviated the persistent itch.
A TSLP inhibitor, tezepelumab, had some disappointing results in a phase 2 clinical trial. Nevertheless trials are still being conducted and trials for asthma have shown favorable results.
Etokimab, is an anti-IL-33 monoclonal antibody which has shown some favorable results. Trials are currently ongoing.
Fezakinumab is an IL-22 blocking monoclonal antibody. The Th22 pathway is considered a key immune driver of atopic dermatitis. Fezakinumab has shown reversal of multiple pathological features of atopic dermatitis skin as well as a reduced overall inflammatory burden.
Ustekinumab, a human monoclona antibody inhibiting the shared p40 subunit of IL-12 and IL-23 is an effective drug for psoriasis because it blocks IL-23. Bimekizumab, another monoclonal specific for both IL017a and IL-17f is also effective for psoriasis.
Baricitinib, a JAK 1/2 antagonist was recently approved for rheumatoid arthritis was was the first oral JAK inhibitor to progress to phase 3 clinical trials for atopic dermatitis. In phase 2 trials, Baricitinib, achieved 50% or more reduction in Eczema scores compared to placebo. Upadacitinib, a selective JAK1 inibitor showed efficacy in phase 3 trials for Rheumatoid Arthritis, clinical trials showed improvement for eczema as well. Abrocitinib is another specific JAK1 inhibitor tested for atopic dermatitis.
Histamine 4 receptor antihistamines has an entirely different mechanism of action. They antagonize H4R, which plays a role in Th2 and Th17 inflammation and itching. ZPL-3893787 showed clinical efficacy on inflammatory skin lesions in eczema. This new class of drugs show a potential as a novel therapeutic option for this disease.
Atopic dermatitis is a heterogenous disease. Different therapeutic approaches may be necessary for different patient subsets, including a personalized approach or dual cytokine targeting. Dupixent is currently the mainstay of treatment until other drugs are approved. Investigations of these various treatments will help dissect the complex contribution of various cytokines to atopic dermatitis and improve long term disease management and prevention of flares.