January 22, 2018

Monoclonal antibodies represent a promising new approach to eczema treatment, a dermatological condition that produces intense skin pain.

With Lindsay C. Strowd MD, and Lynda Schneider, MD

While an itch may be the first symptom of the discomfort of atopic dermatitis (AD), the scratching, skin inflammation, and irritation collectively contribute to skin pain and should be considered in managing this often-chronic condition.1

The clinical experience of atopic dermatitis varies greatly among patients, given the multifactorial pathogenesis, and individualized nature of the known triggers for this painful skin condition. In general, many patients have shown a good response to a treatment regimen that combines an emollient with a topical or systemic therapy. However, patients for whom traditional treatment fails are in need of new therapeutic options.

Monoclonal Antibody Therapy May Hold the Future

The move toward a wider reliance on biologics—protein-based medications developed from genetically modified cells—to manage atopic dermatitis seems to be gaining moment in a growing number of clinical trials.2

The focus on biologics represents a “growing movement towards the use of targeted therapies in treating atopic dermatitis,”3,4 according to co-author Lindsay C. Strowd MD, assistant professor of dermatology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

These biologics, a class of monoclonal antibodies, promise a longer term, more targeted approach, work by findings to small proteins, or cytokines, that appear to block the inflammatory reaction.

Given an observed Th2-related inflammatory response, therapeutics with the ability to interrupt Th2-related molecules may prompt a reduction in inflammation and disrupt the feedback loop (eg, itch, scratch, inflame) common in AD. Instead of suppressing the entire immune system, these agents have the ability to seek out specific molecules.

In effect, this new class of biological drugs, known as monoclonal antibodies, work by binding to specific cytokines, specifically interleukins 4, 17 and 31, said Lynda Schneider, MD, director of the Allergy Program at Boston Children’s Hospital, and professor of pediatrics at Harvard Medical School in Cambridge, Massachusetts.

These three interleukins, or ILs, are known to drive inflammation in moderate to severe eczema, she said.

The predominant early immunologic response in atopic dermatitis includes type 2 helper T (Th2) cells, innate lymphoid cells, and keratinocytes that produce the type 2 cytokines, such as thymic stromal lymphopoietin (TSLP), a major promoter of atopy) and interleukins 4, 13, and 31.3,4 Interleukins 4 and 13 and TSLP inhibit the differentiation of keratinocytes and thereby reduce the production of skin-barrier proteins and epidermal lipids.1

Early Trials of Up and Coming Cytokine Therapies

In a year-long randomized, double-blind, placebo-controlled phase 3 study—Liberty AD Chronos—the results indicated that dupilumab, when added to standard topical corticosteroid treatment, had satisfactory safety and showed improved efficacy for atopic dermatitis in adults.5

Approval of dupilumab—the first such biologic agent to treat atopic dermatitis— is leading the field but faces strong competition in 2018. In fact, a variety of subcutaneous or intravenous biologic agents are currently under investigation to block specific molecules, including interleukin (IL) 4, IL13, and IL17 may gain approval.5-8

The next biologic to watch for is nemolizumab, according to Dr. Schneider who believes this monoclonal antibody holds great promise to bring symptom relief to people with eczema that will support an improved quality of life.4 She based this on study findings showing a dose-dependent reduction in pruritus (used to gauge itch).6

Nemolizumab appeared to work quickly, with a reduction of nearly 30% on a patient-reported visual-analog scale, with a noticeable result in the first week, as compared with only a slight placebo effect.7 While these preliminary results appear promising, larger studies remain necessary to confirm the efficacy and safety of nemolizumab.

A third “mab,”tralokinumab targets the cytokine, IL-13, having been evaluated in asthma patients, where it did not significantly reduce disease severity; however, a subgroup analyses revealed an increased impact of tralokinumab in patients with a high baseline serum level of IL-13 indicating better efficacy in more Th2-polarized disease.8

Another IL-13 specific monoclonal antibody, lebrikizumab, was developed to treat asthma and other inflammatory conditions, but is now under investigation to manage symptoms of atopic dermatitis; positive results n phase 2 studies were sufficient to move forward in testing.9

Although results from these new cytokines appear promising, the need for larger studies to confirm the drug’s efficacy and safety remain, said Dr. Schneider. She also indicated that the new biologics, with all their power and promise, may not work for every patient with eczema because eczema isn’t a single disease.9

“We know that the condition has many clinical subtypes, but these are not well understood,” she said.

Differences in how eczema presents itself and in its underlying pathology may be related to a patient’s ethnicity and age of onset, among other factors.3 In other words, different cytokines may characterize the disease in different patient groups, Schneider explained.

Other topical, oral, and injectable medications in the pipeline are under development to suppress immune targets in atopic dermatitis.

Beyond Efficacy, Need for Accessibly and Affordability

Although these emerging new therapies have the potential to revolutionize the treatment of atopic dermatitis, the extent of their effect on patient care will depend on their affordability and accessibility to patients from a broad range of socioeconomic groups and with different insurance status.10

Getting to the next level in treating eczema will depend on the development of biomarkers: specific molecules that identify a patient’s disease subtype and can be detected with a simple blood test. An accurate map of the relevant cytokines will, in turn, speed up drug development and help physicians tailor treatment to a patient’s specific disease subtype.

For now, Schneider said her best guess is that dupilumab, and, perhaps soon, nemolizumab, could become part of a comprehensive approach to eczema care that includes topicals, patient education on skin care and trigger avoidance, psychological support and direct treatment of sleep disorders and mental health issues.9

“For certain ethnic groups and ages, these immunologic responses may be important in disease persistence,” according to Dr. Scheider, “For the best patient care, these new therapies should be included as part of a comprehensive approach that includes education on skin care and an understanding of triggers, psychological support to enhance adherence and reduce itching, and treatment of the already established mental health and sleep disorders.”

Last updated on: January 22, 2018

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