Dupilumab for severe AD: Expert advocates continuous treatment



This story appears courtesy of MDedge News



LAHAINA, HAWAII – Most patients on dupilumab for the treatment of severe atopic dermatitis respond best on continuous long-term dosing of the selective Th2 cytokine inhibitor rather than treatment on an as-needed basis, Andrew Blauvelt, MD, advised at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“I view atopic dermatitis as a chronic disease requiring chronic treatment. So be very careful about stopping. We know that if you start and stop biologics you’re going to be far more prone to develop antidrug antibodies resulting in drug resistance than with continual dosing,” said Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

He said dupilumab (Dupixent) seldom induces disease remission as defined by clear skin while off all drugs for at least 1 year, although he has a few patients who seem to be exceptions. Yet clearly dupilumab doesn’t change an individual’s predisposing genetics or environmental allergen exposure pattern, so it’s best to think of it as a treatment for the long haul.

Dr. Blauvelt considers dupilumab far and away the best medication for treatment of adults and teenagers whose atopic dermatitis (AD) is uncontrolled with topical therapy. Payers often balk at authorizing dupilumab unless a patient has first undergone an unsuccessful trial of cyclosporine or methotrexate, which are far less expensive. But that’s not what the expert consensus guidelines recommend (Ann Allergy Asthma Immunol. 2018 Jan;120[1]:10-22.e2).

“The guidelines don’t suggest that failure on methotrexate or cyclosporine should be a prerequisite for dupilumab. So if you’re having problems with an insurance company and you really want to use dupilumab, you can point to this paper and say, ‘Look, the experts do not recommend step therapy, we can go directly to dupilumab.’ And the dupilumab label says simply that failure of topical therapy is required before being allowed to use dupilumab. So both the label and the experts say you don’t have to go through a bunch of steps in order to get to what I consider the very best drug for our patients,” he explained.

Both cyclosporine and methotrexate are far more broadly immunosuppressive and hence less safe than dupilumab. Both require laboratory monitoring. In contrast, blood work isn’t required in patients on dupilumab; in fact, Dr. Blauvelt considers it an unwise use of resources. Nor is tuberculosis testing advised prior to starting dupilumab.

When he can’t get authorization for dupilumab, Dr. Blauvelt’s go-to drug is methotrexate at 15-25 mg/week. It’s not as effective as cyclosporine for rapid clearing, but it’s safer for long-term use.

“Methotrexate is the devil we know – we know how to use it, and we know how to monitor for it,” he commented, adding that he reserves cyclosporine for a maximum of a month or 2 of acute crisis management, or as a bridge in getting patients off of systemic corticosteroids.

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.

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.


SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.


By Bruce Jancin
[email protected]