Conference Coverage

Dupilumab for severe AD: Expert advocates continuous treatment


 

EXPERT OPINION FROM SDEF HAWAII DERMATOLOGY SEMINAR

Set realistic efficacy expectations

Dermatologists who prescribe the newest biologics for psoriasis are accustomed to routinely seeing PASI 90 responses and even complete disease clearing. However, AD is a more challenging disease. In the landmark dupilumab phase 3 randomized trials, roughly two-thirds of patients achieved an Eczema Area and Severity Index (EASI) 75 response, with a mean 80% improvement in EASI symptom scores over baseline. Roughly 20% of dupilumab-treated adults with AD achieve disease clearance, and a similar percentage become almost clear. The improvements are durable in long-term follow-up studies.

“Dupilumab doesn’t get a lot of people to zero. They’re not going to be completely clearing their eczema. So they shouldn’t be freaking out if they still have eczema. What they can expect is diminution of the disease to much lower levels,” Dr. Blauvelt said.

The marked improvement in quality of life that occurs with dupilumab therapy isn’t adequately captured by EASI scores. “In my experience, more than 80%-90% of patients are happy on this drug,” Dr. Blauvelt said.

Conference codirector Linda Stein Gold, MD, agreed, commenting that she has found dupilumab to be “absolutely life altering” for her patients with severe AD.

“They know they still have AD, but now they can go whole days without thinking about it,” said Dr. Stein Gold, director of dermatology research and head of the division of dermatology at the Henry Ford Health System in Detroit.

Dr. Blauvelt noted that most of his patients on dupilumab remain on topical therapy, typically with triamcinolone on the body and hydrocortisone on the face. What he terms “miniflares” in patients on dupilumab are not at all unusual, but they’re readily manageable.

“Flares that used to last for weeks now last for a day or 2, maybe 3, and then it’s back to normal in patients on dupilumab,” Dr. Blauvelt said.

Safety

Dupilumab is a targeted inhibitor of interleukins-4 and -13, cytokines involved in allergy-mediated inflammation and the control of parasitic infections, but which have no bearing on control of bacterial or viral infections or malignancies. Indeed, the randomized trials have demonstrated that the incidence of skin infections is actually lower with dupilumab than with placebo.

“You’re improving the skin barrier so much that they’re not going to be getting staph or herpes simplex,” he explained.

The main side effect consists of dupilumab-associated eye issues. These occur in up to 20% of treated patients and encompass a spectrum ranging from dry eye to nonallergic conjunctivitis, inflammation of the eyelid, and keratitis. The mechanism is unknown. The condition is not infectious and doesn’t affect vision. Intriguingly, it doesn’t occur in patients with asthma, a disease for which dupilumab is also approved.

“Ask about eye issues at every office visit,” the dermatologist urged.

He sends all of his AD patients with dupilumab-associated eye issues to a single trusted local ophthalmologist and lets him manage the condition, which is generally mild to moderate. Eye issues have resulted in discontinuation of dupilumab in only 2 of the roughly 150 AD patients Dr. Blauvelt has placed on the biologic. The ophthalmologist generally relies upon lubricating eye drops and a couple of weeks of steroid eye drops or, in some cases, topical cyclosporine 0.05% ophthalmic emulsion, followed by episodic use of the steroid eye drops on an as-needed basis.

Residual facial disease in AD patients on dupilumab can be caused by a variety of causes, including breakthrough AD, rosacea, allergic contact dermatitis, steroid withdrawal, or photosensitivity, with Demodex thought to play a role in some cases.

Dr. Blauvelt reported serving as a scientific adviser to and paid clinical trial investigator for several dozen pharmaceutical companies. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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