Does Atopic Dermatitis Pose an Increased Risk of Acquiring COVID-19?

According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.

“This is an area that will continue to evolve, and further understanding will improve the healthcare advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”

According to Thyssen, professor of dermatology at the University of Copenhagen, Denmark, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection, or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”

Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.

“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”

Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”

Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”

To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom performed a cross-sectional study of 13,162 dermatology patients seen in the UK between June 2018 and February 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).

Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.

Another study, a case-control study of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19-associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.

“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Thyssen said.

In another analysis, researchers evaluated Symphony Health-derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients and the cohort without AD included 397,293 patients. Among AD patients, 8180 were prescribed prednisone, 2793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).

“There can be various explanations for this,” Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”

In other findings, the investigators observed that treatment with dupilumab vs no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).

More recently, researchers evaluated the records the records of 1237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab vs other treatments.

Of the 1237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.

Vaccines and AD

Thyssen pointed out that the risk–benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”

Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly & Co., LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.

The Revolutionizing Atopic Dermatitis symposium. December 11-13, 2021.

Doug Brunk is a San Diego-based award-winning reporter for MDedge and Medscape who began covering healthcare in 1991. He is the author of two books related to the University of Kentucky Wildcats men’s basketball program.

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