Today, people living with atopic dermatitis (AD) are being greeted with more treatment options than ever before. A thrilling array of new drugs are on the way—not just for adults but for children and adolescents as well.
Ever since the U.S. Food and Drug Administration (FDA) approved Dupixent (dupilumab) in March 2017, it signaled the beginning of the “Golden Age of Eczema,” said Dr. Emma Guttman-Yassky, professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai in New York City.
Dupixent is a biologic, an injectable drug that is an antibody used to treat a disease at the immune system level. The human body uses certain types of signaling molecules called interleukins, or ILs, which help our immune system fight off harmful viruses and bacteria.
But for people with atopic dermatitis, their immune system tends to overreact and trigger certain ILs to produce inflammation. Dupixent blocks IL-4 and IL- 13 from binding to their cell receptors, which keeps the immune system from overreacting, thereby lowering inflammation and decreasing symptoms of AD.
Until recently, Dupixent was only approved for adults with moderate to severe AD and for patients with moderate to severe asthma over the age of 12. In March 2019, the FDA approved Dupixent for adolescents with moderate to severe AD between the ages of 12 and 17.
Dupixent was the first biologic therapy approved for moderate to severe AD, “but it won’t be the last,” said Guttman-Yassky.
LEO Pharma’s new biologic, tralokinumab, is currently in phase III. Instead of blocking two molecular targets— IL-4 and IL-13—the drug blocks IL-13 alone. So far, researchers have reported tralokinumab to be highly effective in treating AD in a number of patients.
An entirely new class of drugs targeting the Janus kinase (JAK) family of enzymes, which have been seen to drive abnormal immune responses, also are on the way. Pfizer’s candidate, PF-04965842, a once-daily oral JAK-1 inhibitor for moderate to severe AD, is now in phase III. The FDA flagged the drug as a “breakthrough therapy,” a designation that will accelerate its path to approval.
And baricitinib, Eli Lilly and Incyte’s drug that inhibits both JAK-1 and JAK-2, has recently met its endpoints in two phase III trials. That means it’s en route to FDA approval for the treatment of AD in adults, and if approved, en route to your pharmacy
Promising new AD treatments in phase II clinical trials
Guttman-Yassky defines “promising” in two ways. A promising drug candidate either has a new mechanism of action—a new target or a new way of targeting it—or:
- It’s easier to administer (oral vs. injectable).
- If it’s injectable, it’s taken less often.
- It has longer-term efficacy.
As researchers continue to uncover the underlying factors that drive AD, new targets have come to light. We asked Guttman- Yassky to discuss the top targeted treatments that are currently in phase II. Here’s what we learned.
Several JAK inhibitors have caught the attention of doctors and patients alike. Upadacitinib, engineered by AbbVie Inc., is a once-a-day oral agent that targets JAK-1. Per the data thus far, Guttman-Yassky said, it is proving effective in relieving itch, improving sleep and reducing disease severity.
Asana BioSciences’ JAK inhibitor targets the entire JAK family of enzymes, along with another inflammatory molecule called spleen tyrosine kinase (SYK). The company’s candidate, an oral agent called ASN002, is the only dual inhibitor in the group, meaning it’s designed to block two targets at once, potentially boosting its efficacy.
A second promising AD drug target is the protein OX40. A member of the tumor necrosis factor (TNF) receptor family, OX40 plays a key role in regulating immune function—except when it goes haywire, as it does in AD. Two companies, Glenmark Pharmaceuticals and Kyowa Kirin Pharmaceutical Development, Inc., are conducting phase II trials of their respective OX40 inhibitors.
Epithelial cytokine inhibitors are a third novel class of drugs in phase II. They aim to interrupt the relationship between the cytokine IL-33 and the skin barrier defect that characterizes AD by blocking yet another cytokine called IL-17C.
A driver of inflammation in both psoriasis and AD, IL-17C has been described as a “unique cytokine” that’s produced by skin cells themselves. Bacteria appear to increase its production and reproduction. Novartis is currently testing an agent that has shown promise in curbing IL-17C in AD.
“What all these new agents have in common is that they take longer to work than Dupixent,” Guttman-Yassky said. “That’s because they target factors that are ‘upstream,’ meaning higher up in the inflammatory response. It takes a while for such a drug to actually reach its target. However, their effectiveness in clearing AD symptoms could make it worth the wait.”
Keep in mind that the drugs listed in this article are just a fraction of the treatments currently in the development pipeline. For brevity and space reasons, we focused on the drugs that are for moderate to severe AD and in the later phases of clinical trials, and therefore closer to reaching FDA approval.
There are myriad potential or possible FDA-approval treatments in the early stages of research that explore other potential causes and symptoms of eczema. NEA will continue to keep you posted as these innovative treatments advance through the development pipeline.
Check out our complete listing of drugs at various stages of investigation, including orals, injectables and topicals.
Guttman-Yassky considers the new drug targets potentially revolutionary, and she greets the arrival of new treatments for AD with enthusiasm. That said, she expressed several caveats, particularly that people with AD should have reasonable expectations about treatments.
For starters, Guttman-Yassky emphasized there is still no cure for eczema at this time. A treatment that works for some patients may not work for all patients all the time.
It’s a well-known fact among medical professionals that treatments for other skin conditions, such as psoriasis, tend to clear the skin for a while—even for years, in some cases. However, eventually the body can become immune to their effect, and at a certain point, they may stop working.
The reality is that moderate to severe AD, a condition that is as unpredictable as it is difficult to treat, requires a flexible attitude. Instead of viewing an eczema treatment as a quick fix, Guttman- Yassky said, “think of it as an important part of a combined approach that will likely need to be adjusted over time.”
Back to the Basics: An overview of current AD treatments
If you need a refresher on treatments already available for managing symptoms of atopic dermatitis, don’t worry! NEA has it covered.
Corticosteroids, or “steroids” for short, are drugs that fight inflammation by dialing down the immune system. Steroids can bring short-term relief for the itch, inflammation and dryness that are the hallmarks of the disease. But, if used inappropriately, they can cause a variety of side effects, such as increased blood vessel formation, thinning of the skin and immune system complications. Topical steroids range from weak to extremely potent, and their chemical structure varies as well. Your medical provider will determine the optimal type of steroid for your needs and should monitor you closely for side effects.
Topical calcineurin inhibitors
The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus tackle the full range of AD symptoms—itch, inflammation and dryness—but with fewer side effects than steroids. However, they come with an FDA black box warning regarding an increased risk of cancer associated with their long-term use. According to a 2015 study published in JAMA Dermatology, the warning was based on data linked to the oral calcineurin inhibitors used in organ transplantation. TCIs don’t deserve the black box warning, the authors argued, as many specialists consider these topicals a safer alternative to steroids.
Topical PDE4 inhibitors
Eucrisa (crisaborole) is a phosphodiesterase (PDE4) inhibitor approved by the FDA in December 2016 for mild to moderate eczema. Eucrisa is a topical that works to ease the effects of PDE4, an enzyme believed to be overactive in the skin cells of people with AD. By blocking the PDE4 enzyme, it reduces inflammation on and below the surface of the skin.
Doctors often prescribe antibiotic and antiseptic creams and ointments to deal with bacterial infections. But they do so within strict parameters, mainly due to issues related to antibiotic resistance. Mupirocin, an antibiotic that’s administered topically, is the first line of defense against secondary infection in AD. As with other treatments, the decision to use them depends on a physician’s judgment and the needs of the individual patient.
Prescription skin barrier protectors
These medications often contain lipids such as ceramides, which are natural components of the skin made from fats, oils and waxes. People with eczema have a deficiency of natural lipids, which contributes to dry skin and itching. Prescription skin barrier protection medications help combat moisture loss and prevent irritants from entering the skin.
Phototherapy, which harnesses the power of ultraviolet (UV) light, has long been used as a treatment for inflammatory skin conditions, including psoriasis and eczema. There are two types of phototherapy: UVA and UVB. UVA needs to be combined with psoralen, a light-activated oral medication. It may increase the risk of skin cancer if used long-term. Narrowband UVB therapy is believed to have a better safety profile. The current guidelines recommend phototherapy as a second-line treatment, to be used when topical treatments fail.
Oral prednisone, a commonly prescribed systemic steroid, can improve the skin’s appearance dramatically. But once patients stop taking it, their eczema tends to rebound and their symptoms may be harder to control than before they started on the drug. Specialists may prescribe a short course of prednisone to ease the transition between one treatment and another—say, from a topical steroid to phototherapy. The key is to taper off it gradually to minimize the rebound effect and other undesired reactions.
Note from NEA: Routine use of oral or injectable steroids is generally discouraged and should be reserved for special circumstances.
These powerful drugs are recommended for short-term usage. Even then, patients who take them should be monitored closely for side effects. While some doctors still prescribe them for AD patients, others avoid doing so due to harmful side effects.
- Cyclosporine, for example, may raise blood pressure and cholesterol.
- Methotrexate, considered relatively safe at low doses, is known to interact with a variety of common medications, and may cause potentially serious lung and liver side effects.
- Azathioprine interferes with DNA synthesis. As a result, it can cause a dangerous buildup of an important enzyme in the body of people with AD.
- Mycophenolate mofetil, also known as CellCept, can cause gastrointestinal issues, along with bone marrow and liver toxicity.
Biologic drugs or “biologics” are engineered from proteins derived from living cells or tissues and are taken by injection. The biologic Dupixent (dupilumab) works by targeting a part of the immune system thought to contribute to the symptoms of moderate to severe atopic dermatitis. By reducing the immune system reaction, Dupixent reduces inflammation, which in turn reduces skin redness, itch, and rash associated with atopic dermatitis.
Don’t forget the essentials of eczema care!
- Always consult with your doctor before trying any new product or treatment.
- Be on the lookout for side effects or even for inadequate effects so that your provider can make adjustments to your treatment as needed.
- Learn how to identify and avoid triggers. For more information on tracking triggers, turn to page 4.
- Don’t slack on your skincare regimen. Keeping your skin clean and moisturized is the first step to keeping your eczema in check.
A medical review of this article was performed by Dr. Peter Lio.