Benralizumab Has No Effect on Influenza Vaccine Antibody Response, Study Finds

Benralizumab, an interleukin-5 (IL-5) antagonist used to treat severe asthma, does not weaken antibody response of influenza vaccinations, according to results of a recent study.

Sold under the name Fasenra, the monoclonal antibody targets IL-5, a type-1 cytokine that plays a key role in the triggering eosinophilic airway inflammation. It is used as adjunctive therapy in patients 12 years and older.

By depleting eosinophils proliferation, activation and differentiation, benralizumab has shown to significantly reduce exacerbations and improve lung function. There is some thought that eosinophils may serve a purpose in acquired immunity from viral vaccination and infections. By depleting eosinophils, benralizumab may also negatively alter influenza vaccine response. The phase 3b trial, ALIZE, served to determine whether benralizumab affected the influenza vaccine antibody response.

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One hundred and three patients were randomized to receive benralizumab or placebo. In the benralizumab group, patients received 3 doses of benralizumab 30 mg subcutaneously at weeks 0, 4, and 8. Patients in the placebo group received a placebo injection at the corresponding days as the treatment group. At week 8, all patients received a quadrivalent influenza vaccine. Blood samples were drawn at week 8 and week 12 to determine antibody response. Hemagglutination inhibition (HAI) and microneutralization (MN) antibody assays were used to determine if there were any antibody response differences between the 2 groups. A ≥4-fold increase in post-vaccination antibody titers from week 8 to 12 and a postdose HAI antibody titer ≥40 at week 12 signified an effective influenza vaccination antibody response.

In all patients treated with benralizumab, steady state was reached at week 8 and eosinophil depletion was evident, with an eosinophil mean count of 0.028 x 10⁹ cells/L in the benralizumab group compared to an eosinophil mean count of 0.288 x 10⁹ cells/L in the placebo group.

Patients with positive anti-drug antibodies also had depleted eosinophil counts.

At week 12, there was no significant differences in HAI antibody responses between the 2 groups. Similarly, the percentage of patients with a ≥4-fold increase in HAI antibodies from week 8 to 12 among the 2 groups were comparable (44% to 56% and 30.6% to 49% in patients receiving benralizumab and placebo, respectively). HAI antibody titers ≥40 was achieved in 78% to 100% in the benralizumab patient population versus 79.6% to 100% in the placebo patient population. Responses from the MN antibody assay were also similar between the 2 groups.

The influenza vaccine is important in all patients and is especially important in patients with asthma, in which an influenza infection may predispose an asthma attack. There was concern that an immunomodulator drug, such as benralizumab, may adversely affect the influenza vaccine’s response. However, from this trial, there was no evidence that benralizumab diminished any of the antibody responses from the influenza vaccine. Unless other studies prove otherwise, benralizumab can be used safely without a concern for diminished influenza vaccine response in patients with severe asthma.

Reference

Zeitlin PL, Leong M, Cole J, et al. Benralizumab does not impair antibody response to seasonal influenza vaccination in adolescent and young adult patients with moderate to severe asthma: results from the phase 3b ALIZE trial. J Asthma Allergy. 2018;11:181-192. doi:10.2147/jaa.s172338.