Secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years

Abstract

Background Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL‐17A, a key cytokine involved in psoriasis and psoriatic arthritis development, and has shown rapid and long‐lasting efficacy and safety in the complete spectrum of psoriasis manifestations. Monoclonal antibody therapies may be associated with the production of treatment‐emergent antidrug antibodies (TE‐ADAs) that can affect drug pharmacokinetics, diminish clinical responses via inhibition of target binding or cause hypersensitivity reactions. Secukinumab exhibited minimal immunogenicity up to 52 weeks in patients with moderate‐to‐severe plaque psoriasis, as evidenced by TE‐ADA in <1% patients. Objective To investigate the immunogenicity of secukinumab treatment up to 5 years in two phase 3 extension studies (NCT01640951 and NCT01365455) in patients with moderate‐to‐severe plaque psoriasis. Methods Immunogenicity was evaluated up to Week 268 (5 years). TE‐ADAs were defined as positive antidrug antibody (ADA) signals detected in post‐treatment samples from patients with negative baseline signals. Confirmed positive samples were further analysed for their neutralizing potential. Results In total, 1821 patients entered the extension studies. Among patients receiving secukinumab and evaluated for ADAs (n = 1636), 32 developed TE‐ADA, which resulted in an incidence of new TE‐ADA cases below 1% per year. Neutralizing antibodies were detected in 9/32 (28%) patients with TE‐ADA. Half of ADA‐positive cases were transient. Among pharmacokinetic samples measured at the times of immunogenicity determination (n = 9992), 544 (5.4%) had secukinumab concentrations higher than the drug tolerance level of 53.8 μg/mL. There was no effect of TE‐ADA, including neutralizing antibodies, on efficacy, safety or pharmacokinetics of secukinumab. Conclusion The yearly secukinumab immunogenicity incidence over 5 years of treatment was consistently below 1% in patients with moderate‐to‐severe plaque psoriasis. Any TE‐ADAs, including neutralizing antibodies, were not associated with loss of secukinumab efficacy or with clinical concerns.

T cell epitope mapping of secukinumab and ixekizumab in healthy donors

“… 11 – 18 Furthermore, even without co-treatment (e.g., methotrexate), the clinical immunogenicity incidence (anti-drug antibody [ADA] response) was consistently below 1% in patients with moderate to severe psoriasis treated with secukinumab for up to 5 years. 19 – 21 Secukinumab was also associated with a low incidence (<1%) of immunogenicity in PsA and AS after 1 year of treatment. 22 …”

“…[11][12][13][14][15][16][17][18] Furthermore, even without cotreatment (e.g., methotrexate), the clinical immunogenicity incidence (anti-drug antibody [ADA] response) was consistently below 1% in patients with moderate to severe psoriasis treated with secukinumab for up to 5 years. [19][20][21] Secukinumab was also associated with a low incidence (<1%) of immunogenicity in PsA and AS after 1 year of treatment. 22 Ixekizumab is a humanized IgG4 variant/kappa antibody, obtained by immunizing mice with human IL-17A, selecting specific binders using antigen-binding fragment (Fab)-expressing phage display technology, followed by phage display-based humanization and affinity maturation in E. coli.…”

Long-term follow-up of 22 psoriatic patients treated with ixekizumab after failure of secukinumab

“…In summary, the overall response to ixekizumab as second IL17A blocker is relatively good. Neutralizing anti-drug antibodies to secukinumab appear not to be relevant as a possible explanation for treatment failure to secukinumab [9]. The better effect of ixekizumab might be at least partly explained by the fact that ixekizumab has shown a 50-100 times Dermatology Online Journal || Commentary higher in-vitro affinity to IL17A compared to secukinumab [10,11].…”

Immunogenicity to biological drugs in psoriasis and psoriatic arthritis

“…Neutralizing antibodies were detected in 9 of the 32 patients, half of whom were transient in duration. As an important conclusion, the researchers emphasized that no titer or type of antibodies affected the efficacy, safety, or pharmacokinetics of SCK (65).…”