Atopic dermatitis (AD) is the most common inflammatory skin condition. Commonly known as eczema, it is estimated to affect 10-25% of children and 2-8% of adults in affluent countries, including the U.S. The majority of people with AD can be effectively treated with a combination of emollients (a type of moisturizer), topical or systemic therapies, and behavioral approaches like avoiding triggers and managing itch. However, for a subset of people with AD, the existing treatment options aren’t effective, leading researchers to pursue novel, targeted therapies.1
Complicating the search for effective treatments is the complexity of AD. The chronic condition varies greatly among different patients, leading some to believe that the term AD may be an umbrella term for several different diseases. In different people with AD, there can be unique triggers (or distinct combinations of triggers, varying levels of severity of their disease, and different immune system dysfunctions that are contributing to their disease.1,2
Inflammatory pathways with atopic dermatitis
The inflammatory response of the immune system is designed to protect the body, but in people with AD, the inflammatory response is dysfunctional, causing chronic inflammation in the skin that damages tissue and causes symptoms of AD including itchiness, changes in skin color, and rashes. (Immune system dysfunction is one key factor in the development of AD, with the other known factors being a compromised skin barrier function and environmental factors.) Researchers have been identifying key components in the inflammatory response, including interleukins 4, 13, 17, and 31 and janus kinase inhibitors. Interleukins (IL) are a type of protein that are produced by white blood cells that mediate the immune response. IL-4 and IL-13 have also been identified as having a role in the production of substances that are essential for the skin barrier, including filaggrin, involucrin, and loricrin. Janus kinase (JAK) is a group of enzymes that are involved in the inflammatory process.1,3
Biologic therapies called monoclonal antibodies are being developed to target these ILs. Monoclonal antibodies are created in the lab to bind to specific substances in the body, such as ILs. When the monoclonal antibody finds and attaches to its target IL, it stops the normal action of that IL, such as stopping the overactive inflammatory response. Dupixent® (dupilumab) is the first biologic approved for the treatment of moderate to severe AD in adults. Dupixent inhibits IL-4 and IL-13.1,2,4
Two monoclonal antibody treatments that are currently in clinical trials for AD are tralokinumab and lebrikizumab. Both target IL-13 and were originally developed for treating asthma and other inflammatory conditions. Early studies have suggested that each of these therapies provides a significant improvement in symptoms compared to placebo, and further studies in larger groups of patients are needed to confirm the effects, determine proper dosing, and ensure safety. 3
IL-17 has been found to play a significant role in psoriasis, another inflammatory skin condition, and a smaller role in AD. Because some AD lesions have been found to contain IL-17, some biological therapies that are used in psoriasis are now been studied in people with moderate to severe AD, including secukinumab (brand name Cosentyx) and ustekinumab (brand name Stelara). Trials for secukinumab are still recruiting patients. In a small trial of 33 patients with moderate to severe AD, those treated with ustekinumab showed more improvement that those who received placebo, but the results were not statistically significant.3
Nemolizumab is a monoclonal antibody that targets IL-31. Nemolizumab is currently being studied in adults with moderate to severe AD. An early study of 216 patients promising results. At the end of the 12-week trial, patients who were treated with nemolizumab had a 50% reduction in itch, compared to a 20% reduction in itch experienced by those who received placebo. Additional research is needed in larger groups of patients to confirm the effectiveness and safety.1,2,5
Janus kinase inhibitors
JAK inhibitors have been studied for a number of inflammatory conditions, including rheumatoid arthritis (RA), inflammatory bowel disease, and more recently, moderate to severe AD. JAK inhibitors currently in research in AD include:1,6
Baricitinib – an oral treatment currently in clinical research
Tofacitinib – both a topical formula and an oral treatment are being studied in AD
Upadacitinib – currently being studied as a treatment for AD, RA, and Crohn’s disease
Biologics are one of the most exciting areas of research, as they provide a new way to treat diseases like AD that are more targeted. Targeted therapies that specifically work on pathways that are dysfunctional in the body have the potential to have fewer side effects and offer a new approach for people with moderate to severe AD that has not been effectively treated with traditional approaches. One of the next areas of research will be to identify biomarkers (specific molecules that classify a person’s disease subtype) that can determine the best treatment for each subtype of AD.2
If you are interested in participating in clinical trials for AD and potentially receiving the latest in therapies, you can find a list of trials at ClinicalTrials.gov.
Nygaard U, Vestergaard C, Deleuran M. Emerging treatment options in atopic dermatitis: systemic therapies. Dermatology. 2017;233:344-357. doi: https://doi.org/10.1159/000484406.
Godfrey J. Biologics in the pipeline offer promise for atopic dermatitis. Practical Pain Management. Available at https://www.practicalpainmanagement.com/resources/news-and-research/biologics-pipeline-offer-promise-atopic-dermatitis. Accessed 2/2/18.
Bowser A. Atopic dermatitis: biologics to watch in 2018. Dermatology Times, Modern Medicine. Available at http://dermatologytimes.modernmedicine.com/dermatology-times/news/atopic-dermatitis-biologics-watch-2018. Accessed 2/2/18.
Dupixent product website. Available at https://www.dupixenthcp.com/about. Accessed 2/2/18.
Ruzicka T, Hanifin JM, Furue M, Pulka G, et al, for the XCIMA Study Group. Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. N Engl J Med. 2017;376:826-835.
Frellick M. JAK inhibitors show promise for alopecia, eczema, vitiligo. Medscape. Available at https://www.medscape.com/viewarticle/876855. Accessed 2/2/18.