Incidence of Anti-Drug Antibodies to Monoclonal Antibodies in Asthma: A Systematic Review and Meta-Analysis

BACKGROUND: Antidrug antibodies (ADAs) may worsen the efficacy and safety of biologics. However, little is known about the incidence of ADAs associated with the 6 biologics approved for the treatment of asthma in the United States.OBJECTIVE: To elucidate the incidence of ADAs and their impact on reported clinical outcomes.METHODS: Systematic review and meta-analyses of randomized controlled trials, open-label extension studies, and nonrandomized studies of biologics in patients with asthma indexed in PubMed, Embase, and CENTRAL between January 1, 2000, and July 9, 2022, were carried out. The primary outcomes were treatment-emergent ADAs (incidence) and ADA prevalence.RESULTS: A total of 46 studies met the eligibility criteria. ADA incidence over follow-up was 2.91% (95% CI, 1.60-4.55) and was highest in the benralizumab studies (8.35%), with a risk ratio of 4.9 (2.69-8.92) when compared with placebo, and lowest in the omalizumab studies (0.00%). Incidence was 7.61% in the dupilumab studies, 4.39% in reslizumab, 3.63% in mepolizu-mab, and 1.12% in the tezepelumab studies. Incidence of neutralizing antibodies was 0.00% to 10.74% and was highest for benralizumab (7.12%). Incidence of neutralizing antibodies was higher in the benralizumab every 8 weeks (8.17%) versus every 4 weeks arms (5.81%). Results were consistent in subgroup analyses by study type and length of follow-up.CONCLUSIONS: Approximately 2.9% of individuals in the included studies developed ADAs over study follow-up period. The incidence was highest in the benralizumab group and lowest in the omalizumab group. The subcutaneous route and longer dosing intervals were associated with higher ADA devel-opment.(C) 2023 American Academy of Allergy, Asthma & Immunology

Automated summary

This study aimed to determine the incidence of antidrug antibodies (ADAs) and their impact on clinical outcomes in patients with asthma receiving biologics. The results showed that the overall ADA incidence was 2.91%, with benralizumab having the highest incidence (8.35%) and omalizumab having the lowest incidence (0.00%). The subcutaneous route and longer dosing intervals were associated with higher ADA development.