Journal Article

Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis

Lai, Ching-Ha, Davis, John D., Stahl, Neil, DiCioccio, A. Thomas, Rajadhyaksha, Manoj, Maloney, Jennifer, Kanamaluru, Vanaja, Kosloski, Matthew P., Richards, Susan M., Shabbir, Arsalan, Torri, Albert, Akinlade, Bolanle, Yan, Hong, Shumel, Brad, Rodríguez-Marco, Ainara, Khokhar, Faisal A., Babilonia, Elisa, Bansal, Ashish, Ardeleanu, Marius, Kamal, Mohamed A., Partridge, Michael A., Gherardi, Guy, Mortensen, Eric, Xu, Christine R., Xiao, Jing, Braunstein, Ned

2024

Overview

Development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety. To describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD). This analysis included seven phase 3 randomized, placebo-controlled (N=2,992) and two long-term open-label extension (N=2,287) trials of subcutaneous dupilumab in adults and pediatric patients with moderate-to-severe AD. ADA, NAb, and dupilumab concentration in serum were assessed using validated immunoassays. ADA impacts on efficacy (EASI) and safety were assessed. Treatment-emergent ADAs were observed in up to 8.6% (aged ≥18 years), 16.0% (12-17 years), 5.3% (6-11 years), and 2.0% (6 months to 5 years) dupilumab-treated patients. Among dupilumab-treated patients, ≤3.7% had persistent responses, <1% had high titers (≥10,000), and ≤5.1% were NAb-positive. NAbs were more common in patients with moderate- and high-titer ADA responses. High-titer ADAs, while infrequent, were the variable most associated with lower dupilumab concentrations in serum and loss of efficacy, independent of NAb status. Efficacy was generally similar in ADA-positive and -negative patients. For most patients with high- or moderate-titer ADAs, titers decreased and efficacy improved over time with continued dupilumab treatment. ADA-positive and -negative patients had similar incidences of treatment-emergent and serious treatment-emergent adverse events. One patient with high-titer ADAs developed serum sickness. In patients with AD, ADAs and NAbs had minimal impact on dupilumab concentration, efficacy, and safety, except for high-titer ADAs in a small number of patients. ClinicalTrials.gov, identifiers (NCT02277743, NCT02277769, NCT02260986, NCT02395133, NCT01949311, NCT03054428, NCT03345914, NCT02612454, and NCT03346434).

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: ADA / Adolescent / Adult / Adults / anti-drug antibody / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - pharmacokinetics / Antibodies, Monoclonal, Humanized - therapeutic use / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / Atopic dermatitis / Child / Child, Preschool / Clinical trials / Dermatitis / Dermatitis, Atopic - blood / Dermatitis, Atopic - drug therapy / Dermatitis, Atopic - immunology / Drug dosages / dupilumab / Female / Humans / Immunogenicity / Immunology / Male / Middle Aged / Monoclonal antibodies / neutralizing antibody / Patients / Pediatrics / Pharmacokinetics / Serum sickness / Teenagers / Treatment Outcome / Young Adult