Atopic Dermatitis : Patients with moderate to severe disease likely to require more than topical the
Biologic agents and novel topical treatments for atopic dermatitis (AD) are being eagerly anticipated by practicing dermatologists and Canadian patients with AD, particularly those patients who are not controlled with existing therapies.
“The majority of patients will do well on corticosteroids and/or calcineurin inhibitors,” said Dr. Melinda Gooderham, a dermatologist and Medical Director of the Skin Centre for Dermatology in Peterborough, Ont.
“But patients who have moderate-to-severe presentations will have to look to systemic therapies and will not do as well on [topical] corticosteroids and calcineurin inhibitors."
Traditional systemic therapies such as methotrexate, cyclosporine or oral corticosteroids, while “more accessible from the point of view of cost,” are not designed for treating chronic AD, leaving an unmet need for long-term treatment options, Dr. Gooderham said.
“Monoclonal antibodies are more targeted and do not share the same risk profile of end-organ toxicity that the older [systemic] agents possess,” she explained, citing end-organ toxicity as a serious adverse event that can result from ongoing treatment with oral corticosteroids, methotrexate or cyclosporine.
"It's ideal to put patients on the safest therapy that does not cause any organ toxicity,” she said during an interview with DERM.city
Dupilumab expected soon
One of the newest monoclonal antibodies is dupilumab, a therapy that inhibits the actions of IL-13 and IL-4 and targets the inflammatory nature of AD. It is now available for prescription in the U.S. for the treatment of moderate-to-severe AD, and is expected to be available for prescription in Canada before the end of 2017.
“It’s a great therapeutic opportunity for patients who have severe AD,” said Dr. Danielle Marcoux, a pediatric dermatologist at Sainte Justine Hospital in Montreal and a professor of pediatrics at the University of Montreal. “It will provide a huge relief for patients.”
Dr. Marcoux is involved in pediatric dermatology trials, investigating the safety and efficacy of various biologic agents. But for many pediatric patients, therapies such as topical corticosteroids and calcineurin inhibitors will remain the mainstay of treatment, she noted, adding that improved patient education can help to optimize treatment and achieve better results.
“Many parents have a phobia regarding the use of corticosteroids,” said Dr. Marcoux. “They often start treatment [of their children] as late as possible and finish treatment as early as possible.”
It is incumbent upon health professionals to effectively communicate the strategy regarding optimal application of topical treatments for AD— such as topical corticosteroids—to parents of children who have AD, stressed Dr. Marcoux.
“We know [poor communication about treatment application] is one of the reasons for treatment failure,” Dr. Marcoux told DERM.city.
Other reasons for treatment failure include decreased literacy among parents. Dr. Marcoux pointed to the example at the Children’s Hospital of Eastern Ontario in Ottawa, where Dr. Michele Ramien and Dr. Nordau Kanigsberg developed an illustrative Eczema Action Plan, which was created to target parents who have poor literacy. The impact of the program on improving treatment outcomes will be evaluated in the future.
Caregivers may not understand
The role of topical agents such as corticosteroids in maintenance therapy, where they are applied not only to manage flares, needs to be communicated to caregivers of children with AD, Dr. Marcoux emphasized.
Another topical agent recently included in the AD armamentarium is crisaborole, a small-molecule, boron-based inhibitor of phosphodiesterase-4 (PDE4) and approved by the U.S. Food and Drug Administration for use in mild-to-moderate AD. It is expected to become available in Canada in the near future.
Seven trials have been conducted examining the impact of crisaborole for the treatment of AD, showing improvements in pruritus and improvements in objective efficacy assessments. Additionally, the therapy had no impact on skin thinning (Expert Rev Clin Immunol 2017; 13(5):415–423).
Because it is a topical agent, it avoids the potential side effects such as gastrointestinal adverse events, sometimes associated with systemic PDE4 inhibitors.
“It is another non-steroid option for patients,” said Dr. Aaron Drucker, a Toronto-based dermatologist and assistant professor of dermatology at Brown University in Providence, R.I. “It may not clear someone with severe disease, but it is a good alternative for people with mild or moderate disease, particularly on sensitive body sites.”
Other treatments being explored for moderate-to-severe presentations of AD include mepolizumab, an anti IL-5 agent that is already approved in Canada for the treatment of eosinophilic asthma. The current exploration of mepolizumab is in patients with elevated numbers of eosinophils. “If you don’t have high levels of eosinophils, you will not be included in the study,” said Dr. Gooderham.
Still other monoclonal antibodies that are being investigated for AD in clinical trials include the IL-13 antagonists tralokinumab and lebrikizumab. Data presented to date suggest targeting IL-13 may a be promising avenue for safe and effective management of AD.
Dr. Mariusz Sapijaszko, medical director at Youthful Image Clinic in Edmonton, is enthused about the prospect of new options for treating AD as greater insights about the pathways involved in the disease emerge.
More selective therapies on horizonÉ
“I think there will be other biologic agents studied, developed and approved for AD,” said Dr. Sapijaszko. “The more we know immunologically, the more there is an opportunity to look for selective targets.”
Patients with AD are also more prone to develop irritant contact dermatitis because their skin barrier is not as robust as individuals who do not have AD, noted Dr. Sapijaszko.
Another facet of treating AD is addressing the skin microbiome. Research has shown that the microbiome of patients with AD is not as diverse as those without AD and is dominated by Staph aureus.Studies are ongoing looking at avenues to normalize the skin microbiome in patients with AD, so that the natural diversity of the bacteria on the skin is restored and Staph aureusis not the dominant player in the skin microbiome.
“Some research has shown that if you normalize the microbiome, you can improve the eczema,” noted Dr. Drucker.
Dr. Marcoux agrees that investigations into replenishing the diversity of the microbiome are interesting but the data are not yet robust enough to recommend usage of any topical therapies to prevent AD. “o replenishing the diversity of the microbiome are interesting but the data are not yet robust enough to recommend usage of any topical therapies to prevent AD.
“More studies are required to explore restoring the diversity of the microbiome in inflammatory diseases,” added Dr. Marcoux.
A recent investigation looked at the use of a cosmetic lotion containing heattreated Lactobacillus johnsoniiNCC 533 (HT La1) on the colonization of Staph aureusin patients with AD. Investigators found three weeks of application of the lotion containing HT La1 to the skin of patients with AD controlled colonization of Staph aureusand was linked to clinical improvement (Clin Cosmet Investig Dermatol 2017 Jul 3; 10:249–257).
Non-proprietary and brand names of therapies: pimecrolimus 1% (Elidel, Valeant Canada); tacrolimus (Protopic, LEO Pharma); dupilumab (not approved in Canada); crisaborole (not approved in Canada); mepolizumab (not approved in Canada); tralokinumab (not approved in Canada); lebrikizumab (not approved in Canada).
Originally published in The Chronicle of Skin & Allergy (Aug. 2017; 23(5):page 1,4,6)