麻豆传媒

In March 2017, dupilumab (Dupixent) was approved by the FDA to treat moderate-to-severe atopic dermatitis (AD) in patients in whom topical corticosteroids either were not recommended or had failed to control disease.

Since then, reports of new or worsening psoriasis in adults with AD treated with the monoclonal IgG4 antibody have surfaced. Now results from the of the literature through April 3, 2021, including 3 of the largest cohort studies to date, shed light on the development of psoriasis in patients with AD receiving dupilumab.

In the review, published in the Journal of the American Academy of Dermatology, data from 26 studies and a total of 45 patients revealed that 91% had been prescribed dupilumab for AD. One patient with asthma received dupilumab as well as 1 patient with alopecia areata and 2 with non-atopic dermatitis.

The study authors found that after initiation of dupilumab therapy, the mean latency period for the onset of psoriasis was 3.7 months. Dupilumab was discontinued in 16 out of 33 patients (48%) who developed psoriasis, with 10 of 25 (40%) patients having complete resolution of psoriasis following treatment or dupilumab discontinuation. Varying degrees of improvement were reported in 12 out of 25 patients (48%), and stable or recurrent disease was reported in 3 patients (12%). In 12 patients for whom complete outcome data were available, 2 experienced of psoriasis after discontinuation of dupilumab, 8 showed some improvement, while 2 showed no improvement.

The analysis, led by Matthew J. Zirwas, MD, of the Ohio University Heritage College of Medicine in Athens, also revealed that the incidence of new-onset psoriasis in patients with AD treated with dupilumab is 1.7% -- similar to the prevalence of psoriasis in the general population.

"This suggests that individuals with AD have the same genetic risk for psoriasis predisposition as the general population, and the infrequent coexistence of the two diseases is therefore due to mutually antagonistic ," the study authors wrote. "If this interpretation is correct, AD therapies that do not target IL-4 [Interleukin 4] would not be expected to trigger the development of psoriasis, but this remains to be seen. Future study is warranted to determine the pathogenic mechanisms of this adverse cutaneous reaction to dupilumab."

Although the immunologic mechanism underlying dupilumab-induced psoriasis in AD remains unclear, the authors noted that the role of IL-4 over-expression in AD is well known. Dupilumab may release this inhibition by blocking IL-4 signaling, allowing an underlying predisposition to psoriatic inflammation to emerge.

"This explanation is consistent with the long known observation that co-existence of psoriasis and AD in the same patient is less common than would be expected based on the prevalence of the two diseases," Zirwas and colleagues wrote.

In the following interview, Zirwas -- who founded the Bexley Dermatology Research Clinic in 2017 and is a member of Dermatologists of Central States -- discussed the findings in greater detail.

What led you to undertake this particular study?

Zirwas: I had several patients who developed psoriasis shortly after initiating dupilumab and have been following the literature closely on the topic.

Did you anticipate that the incidence of new-onset psoriasis in dupilumab-treated patients would be similar to that found in the general population?

Zirwas: I truly didn't know. It was part of the reason we did the systematic review to determine whether preliminary work showing this was supported widely.

What were the limitations of your review?

Zirwas: Our review was limited by the small number of studies and the lack of detailed case descriptions for some patients. Also, some cases described as psoriasiform may not have met the true definition of psoriasis.

Once dupilumab was discontinued, how long did it take to resolve or stabilize new-onset psoriasis?

Zirwas: The publications were too inconsistent in how they reported the results for us to be able to determine this. I haven't discontinued dupilumab in any of my patients so I also can't answer based on my clinical experience.

Any thoughts on the varying degrees of improvement after dupilumab was discontinued?

Zirwas: Initially I was surprised that the psoriasis didn't resolve in everyone when the dupilumab was stopped. But the hypothesis was that these individuals always had T-cells predisposed to psoriasis that were suppressed by the IL-4 over-expression associated with atopic dermatitis. When the IL-4 induced suppression was removed and they became active, it may have been a durable change in phenotype and activity of that set of T-cells.

Did any patients appear particularly vulnerable to the onset of psoriasis, such as older patients or those with a history of psoriasis?

Zirwas: There haven't been enough cases to really determine if there are predictors of risk, such as age. If I did have a patient with a history of psoriasis, I'd be very hesitant to start them on dupilumab and would, at a minimum, make sure they were aware of the possibility of a flare.

What is your message to physicians about the clinical implications of your findings?

Zirwas: The most important clinical take-away is that this is not a rare event. Approximately 1 in 50 patients on dupilumab [experience new-onset or recurrent psoriasis] and when this happens, it is reasonable to continue the dupilumab while treating the psoriasis, rather than automatically stopping the dupilumab.

What's next for your research?

Zirwas: I am fascinated to see whether the same phenomenon occurs with tralokinumab (Adtralza), which is an IL-13 only inhibitor. My guess is that it won't. I'm also very interested to see if the development of psoriasis in patients on dupilumab will affect the course of atopic dermatitis. I could imagine it being the case that atopic dermatitis [in patients who develop psoriasis] does better or worse, on average, than in patients treated with dupilumab who don't get psoriasis.

It is such a fascinating time in dermatology. We are learning so much about atopic dermatitis including which therapies work and the consequences of blocking different cytokines.