Secukinumab, an Anti–Interleukin-17A Monoclonal Antibody, Exhibits Minimal Immunogenicity in Subjects with Moderate to Severe Psoriasis

The pro-inflammatory cytokine interleukin (IL)-17A plays a pivotal role in psoriasis pathogenesis. Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, has been demonstrated to be highly efficacious in the treatment of moderate to severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. mAb therapies may be associated with production of anti-drug antibodies (ADA) that can affect drug pharmacokinetics, diminish response, or cause hypersensitivity reactions. Secukinumab immunogenicity in plaque psoriasis subjects exposed to secukinumab was evaluated at Baseline and at Weeks 12, 24, and 52 in 6 phase 3 studies. Treatment-emergent ADA (TE-ADA) were defined as a positive ADA signal detected in post-treatment samples from subjects with a negative baseline signal. Confirmed positive samples were further analyzed for drug-neutralizing potential. Among 2,842 subjects receiving any dose of secukinumab during the 6 phase 3 studies and evaluated for ADA up to 60 weeks, 11 subjects developed TE-ADA. Correlations between TE-ADA and secukinumab dose, frequency, or mode of administration were not observed. Neutralizing antibodies were detected in 3 of 11 subjects with TE-ADA. Development of TE-ADA or neutralizing antibodies was not associated with loss of secukinumab efficacy or other issues of clinical concern