This article provides a detailed overview of eczema treatment in adults, including the causes of this inflammatory skin disorder, whether it is contagious, and the latest medications that have been used to treat eczema in the clinic, including Dupilumab, Tralokinumab, Abrocitinib, and Difamilast, among others.
- What is eczema and what causes breakouts?
- Is eczema contagious?
- Eczema Treatment: Newest Medications
- How could this skin disorder be cured?
What is eczema and what causes breakouts?
Eczema, also known as dermatitis, is a group of conditions involving the inflammation of the skin, including atopic dermatitis, stasis dermatitis, irritant contact dermatitis, and allergic contact dermatitis. While all of the conditions involve an immune response, the causative factors and traits of the associated immune response vary.
In stasis dermatitis, fluid build-up resulting from poor blood circulation leads to skin discoloration, redness, and ulceration. Irritant contact dermatitis is caused by the exposure of the skin to physical irritants such as friction, environmental factors such as water, or chemicals including solvents and detergents. Allergic contact dermatitis involves a particular type of immune response, known as an allergic reaction, at the site of exposure to substances called allergens.
Atopic dermatitis, the most common form of eczema, also involves an immune response to certain substances, but may occur at sites other than that of exposure. While the immune response involved in allergic contact dermatitis is temporary, resulting from contact with allergens and resolving after the cessation of exposure, that of atopic dermatitis is longer-lasting.
Atopic dermatitis, also known as atopic eczema, can lead to itchiness, cracking, scaling, skin rashes, swelling, and other symptoms. Typically the disease cycles through periods of increased symptom severity, known as flares, and times of improvement called remission.
The exact causes of atopic eczema are currently not known. Although people of all ages can be affected, the disease usually develops during childhood and, for many patients, symptoms disappear by adolescence. People diagnosed with atopic eczema frequently have other medical problems including allergies, asthma, depression, anxiety, sleep loss, and other disorders associated with the skin.
Atopic eczema has been attributed in part to genetic patterns and changes, alterations in the behavior of the immune system, poor skin permeability, and environmental factors including air pollutants, soaps, perfumes, cosmetics, wool clothing, chemicals, and cigarette smoke.
Is eczema contagious?
Eczema is not contagious and cannot be transmitted between people. Stasis dermatitis may result from problems with the heart or vasculature that lead to poor blood flow. These anatomic or physiologic problems, resulting from lifestyle, environmental, or genetic factors, are not transmissible.
Irritant and allergic contact dermatitis are caused by exposure to specific substances, and resolve after the removal of the inflammation-causing materials.
While the causes of atopic dermatitis are not clear, the disease is not regarded as contagious. Over 15 million adults and children in the United States are estimated to have atopic eczema, with the incidence of the disease almost tripling over the past three to four decades.
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Eczema Treatment: Newest Medications
Currently, eczema treatment focuses on stabilizing and reducing inflammation and dryness in the skin and preventing future flares. A combination of therapies including over-the-counter topical medications, skin care products and cream such as moisturizers, regular bathing, dietary changes and supplements, and phototherapy using ultraviolet light have been used to treat the disease. When these measures are not effective, patients may require treatment with systemic immunosuppressive prescription medications such as oral medicines and monoclonal antibodies.
The eczema treatment strategy that your physician employs should be personalized and fit your personal circumstances and goals. While some patients may experience a quick resolution of symptoms following treatment, existing therapies are not universally effective and alternative approaches may be warranted. Your physician should be able to provide detailed recommendations regarding new and existing drugs.
Although the exact causes of atopic eczema are unknown, research indicates that molecules associated with the immune system have important roles in the pathogenesis of the disease, and the medical community has attempted targeting a few of these molecules therapeutically, with a particular focus on preventing the expression of or directly inhibiting immune signalling molecules known as cytokines.
The interleukin 4 receptor (IL-4R) inhibitor Dupilumab, marketed under the name Dupixent, is a monoclonal antibody approved in the United States for the treatment of moderate-to-severe atopic dermatitis. The medication functions by binding to a subunit of the IL-4 receptor to prevent signalling pathways that would normally result from the exposure of immune cells to the cytokines IL-4 and IL-13. Dupilumab has been evaluated in multiple phase 3 trials.
The monoclonal antibody tralokinumab, which targets and inhibits the cytokine interleukin 13 (IL-13), demonstrated efficacy for the treatment of atopic eczema in a phase 2b clinical trial. In this study of 204 adults with the disease, eczema treatment with tralokinumab was associated with “early and sustained improvements” in symptoms and “acceptable” safety and tolerability. The results of the trial were published in the Journal of Allergy and Clinical Immunology in 2019.
In December 2019, Denmark-based Leo Pharma announced the completion of three phase 3 clinical trials evaluating the safety and efficacy of tralokinumab for treating moderate-to-severe atopic dermatitis in adults. The results of the randomized, multicenter, placebo-controlled, double-blind clinical trials, called ECZTRA 1, ECZTRA 2, and ECZTRA 3, are expected to be published in 2020.
Executive Vice President of Global Research and Development at LEO Pharma Dr. Kim Kjoeller stated, “In its moderate-to-severe form, AD can cause unbearable recurring symptoms for patients. Despite recent treatment advances, we consistently hear from healthcare professionals around the world that additional treatment options are needed to address the different signs and symptoms for each patient. We are encouraged by these study results, which show that tralokinumab could be an efficacious and well-tolerated long-term treatment solution for patients living with this debilitating chronic skin disease.”
Another medication known as Abrocitinib, which inhibits the activity of the protein janus kinase 1, has been evaluated for the treatment of atopic dermatitis in multiple clinical trials. Janus kinase 1, which is expressed by immune cells, is thought to control the production of multiple cytokines including interleukin-13 involved in disease pathogenesis. A randomized phase 2 study published in JAMA Dermatology in December 2019 found that the daily administration of oral abrocitinib to adults with moderate-to-severe disease was “effective and well tolerated for short-term use.”
The top-line results of a phase 3 clinical trial (JADE MONO-1) assessing the use of abrocitinib for the treatment of atopic dermatitis were announced by Pfizer in October 2019. According to the press release, the doses of the drug evaluated in the study were “well tolerated” and the therapy satisfied all “co-primary and key secondary endpoints.”
Chief Development Officer of Inflammation & Immunology at Pfizer Global Product Development Dr. Michael Corbo PhD stated, “We are pleased by these findings, which together with the recently reported positive top-line results from our second Phase 3 trial, encourage us that, if approved, abrocitinib may provide the first oral, once-daily treatment option for these patients.”
Another drug, difamilast, targets the protein phosphodiesterase 4 (PDE4), which is involved in the production of pro-inflammatory cytokines by immune cells. The medication was discovered by Japanese pharmaceutical company Otsuka Pharmaceutical Co., Ltd., and developed as an ointment for topical application.
In March of 2020, Otsuka announced the results of two randomized phase 3 clinical trials evaluating the efficacy and safety of difamilast (OPA-15406) for the treatment of atopic dermatitis. The studies, one of which involved pediatric patients and the other adults, were conducted at multiple sites in Japan and involved the application of difamilast or a control medication twice daily for four weeks.
Both trials revealed statistically significant improvement according to a symptom severity score without major adverse events. Difamilast commercialization, development, and manufacturing rights in the United States were licensed to New Jersey-based Medimetriks, Inc., by Otsuka in 2016.
Chairman and CEO of Medimetriks Bradley Glassman stated, “We are excited about the results announced today by Otsuka and believe these results further validate the potential for MM36 (difamilast) as a best in class treatment for patients suffering from mild to moderate atopic dermatitis. We are preparing for our US Phase 3 MM36 (difamilast) trials and are committed to our goal of helping improve the lives of atopic dermatitis patients in the United States.”
How could this skin disorder be cured?
Allergic contact dermatitis could be prevented by training the immune system to avoid an inflammatory response to key allergens. This is the goal of allergen immunotherapy and has been studied in the context of food and environmental allergies.
Curing atopic dermatitis will require an improved understanding of the underlying immune response, and fine-tuning of the immune system to avoid unwanted effects. A few of the medications addressed in this article represent progress towards this goal.
Understanding the behavior of key immune cell populations, such as regulatory T cells, within the skin will contribute to the development of better eczema medications. Eczema treatment may change considerably as new medications are approved for use in the clinic.