Study Finds No Link Between Adalimumab, Secukinumab and COVID-19 Vaccine Immune Response

A study published in Lancet Rheumatology found that neither adalimumab nor secukinumab substantially affected a patient’s immune response to the Pfizer COVID-19 vaccine.

According to the authors, patients with axial spondyloarthritis receiving either of these biological disease-modifying antirheumatic drugs (DMARDs) were able to develop cellular immune responses after vaccinations, and there was no significant difference between cellular and humoral immune responses.

Patients receiving immunosuppressive treatment throughout the COVID-19 pandemic have been shown to be at higher risk of severe disease outcomes, and while vaccination could prevent these outcomes, there is no clear understanding yet of the efficacy of mRNA vaccines in these patients.

“Although studies investigating the effect of biological DMARDs on the development of immune responses to COVID-19 vaccines are slowly accumulating, most of our current knowledge relies on studies evaluating the serological responses to COVID-19 vaccines,” the study authors said.

However, they also noted the high variability in serological response in terms of antibody titers and kinetics, as well as the lack of a clear cutoff value of antibody titers that demonstrates protection from the virus.

Past research has demonstrated patients’ ability to elicit both serological and cellular responses to the Pfizer vaccine while being treated with adalimumab or secukinumab. Based on these findings, the authors conducted a study to evaluate the immunogenicity of 2 doses of the Pfizer vaccine in participants receiving monotherapy with either adalimumab or secukinumab.

The study included only 17 patients with axial spondyloarthritis who were not exposed to COVID-19, with 10 being treated with adalimumab and 7 receiving secukinumab. The mean (SD) age was 39.8 (9.4) years and the mean disease duration was 97.3 (80.8) months. Fifteen of the participants were men and 11 of the participants were treated for radiographic axial spondyloarthritis. Six healthy individuals were included in the control group for comparison, made up of 3 men and 3 women.

All participants received the primary vaccine series with a 21-day interval between doses and continued with their respective treatment throughout the study. Humoral immune responses were evaluated by measuring titers of IgA and IgG antibodies that fight off COVID-19 infection, and cellular immune response was evaluated by flow cytometry.

The authors further explained that “the cellular immune response was assessed as the proportion of SARS-CoV-2-reactive CD4+ and CD8+ T cells producing interferon γ, TNF, or IL-17A after ex vivo stimulation with spike glycoprotein-derived peptides (PepMix SARS-CoV-2) and co-stimulation with CD28 and CD49d antibodies. CD107a expression was assessed as an indicator of CD8+ T-cell degranulation.”

Among other findings, the authors found unique differences in the cellular immune responses to full vaccination among the participants, with T-cell responses undetectable in up to 20% of participants receiving the vaccine in both groups.

“We observed a robust seroconversion in all study participants,” they said. “Vaccination also generated proinflammatory cytokine-producing CD4+ and CD8+ T cells, with no significant differences in the proportion of SARS-CoV-2-reactive T cells between the study groups. The second dose of the BNT162b2 [Pfizer] vaccine did not elicit CD8+ T-cell degranulation in patients treated with adalimumab nor in those treated with secukinumab.”

The authors noted small sample size, lack of assessment of neutralizing antibody titers, and specific time period during the pandemic as major limitations in the study.

“We presume that the magnitude of cellular and humoral immune responses might change over time and thus further investigations are needed to fully understand the consequences of biological DMARD therapy in the era of COVID-19,” they said.

Reference

Smetanova J, Strizova Z, Sediva A, Milota T, Horvath R. Humoral and cellular immune responses to mRNA COVID-19 vaccines in patients with axial spondyloarthritis treated with adalimumab or secukinumab. Lancet Rheumatol. Published online December 21, 2021. doi:10.1016/S2665-9913(21)00393-3