Biologics for asthma, atopic dermatitis associated with reduced COVID-19 vaccine responses

NASHVILLE, Tenn. — Patients on biologic therapies for severe asthma or atopic dermatitis had lower pseudovirus neutralization 6 months after receiving the second dose of mRNA COVID-19 vaccines, according to a study presented at CHEST 2022.

Clinicians should then encourage these patients to get booster doses of these vaccines to ensure protection against the disease, Martin C. Runnström, MD, a fourth-year fellow at Emory University School of Medicine, and colleagues wrote.

“Patients with asthma or atopic dermatitis on biologic treatments receive immunomodulatory agents that target various cytokines critical for their respective disease pathogenesis, but which also play important roles in normal immunity,” Runnström told Healio.

IL-4, which is important for antibody class switching and IgE plasma cell differentiation, has complex roles in lymph node germinal center responses, Runnström said.

Also, IL-5 plays important roles in plasma cell survival directly through the expression of the IL-5 receptor on plasma cells or indirectly through survival cytokines such as APRL secreted by eosinophils, he continued.

Martin C. Runnström

“All of these factors are ultimately important for antibody production and protection against disease,” Runnström said.

Previously, the researchers had found that patients with severe asthma or AD who were using biologic therapies had reduced humoral responses 3 months after receiving second doses of mRNA vaccines for COVID-19, compared with healthy controls.

Conducted between February 2021 and February 2022, the current prospective, observational trial evaluated the level and the function of these antibodies 6 months after receiving the second dose.

The cohort comprised five adults treated with benralizumab (Fasenra, AstraZeneca), three adults treated with mepolizumab (Nucala, GSK) and 20 treated with dupilumab (Dupixent, Sanofi Genzyme/Regeneron) for severe asthma or AD in addition to 34 healthy controls.

Using a pseudotyped lentivirus, the researchers analyzed pseudovirus neutralization against wild-type, delta variant and omicron variant SARS-CoV-2.

The patients on biologics had a 2.313 log¹⁰ mean 50% inhibitory dilution against wild-type SARS-CoV-2, whereas the healthy controls had a 2.743 log¹⁰ result (P < .0001). The neutralizing antibody titers against the delta and omicron variants were lower for the patients on biologics as well.

“We found that our cohort of patients with severe asthma or atopic dermatitis on biologics had reduced neutralizing antibodies against wild-type and delta variant SARS-CoV-2 up to at least 6 months after the second vaccination, compared to healthy controls,” Runnström said.

“Additionally, at the same time point, very few healthy controls and almost no patients on biologics had detectable neutralizing activity against omicron variant SARS-CoV-2,” he continued.

Noting that severe or active asthma has been associated with worse COVID-19 outcomes and that lower humoral immunity after vaccination has been associated with less protection, the researchers said that patients taking biologics for severe asthma or AD remain at high risk for severe disease and should be encouraged to get booster vaccinations.

“Our data suggest that severe asthmatics and atopic dermatitis patients may not respond as well to the COVID-19 vaccine as healthy individuals do and may be less protected. They should therefore strongly consider getting booster vaccinations and using other protective measures,” Runnström said.

Further, the researchers said, this better understanding of who remains at high risk for severe infection despite vaccination and who may need additional boosters is critical for controlling the COVID-19 and future pandemics.

“We are continuing to study our cohort of patients with different assays, including cellular immunity using spectral flow cytometry. We are also conducting studies to evaluate what effects these biologics have on modifying the epigenetics of different immune cells,” Runnström said.

“Future studies should aim to recruit a larger number of patients, in addition to having a healthy control cohort and severe asthma or atopic dermatitis cohort that is not on biologics,” he said.

References:

• Runnström MC, et al. Am J Respir Crit. 2022;doi:10.1164/rccm.202111-2496LE.
• Runnström MC, et al. Chest. 2022;doi:10.1016/j.chest.2022.08.2166.