Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years
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Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years. / Reich, K; Blauvelt, A; Armstrong, A; Langley, R G; de Vera, A; Kolbinger, F; Spindeldreher, S; Ren, M; Bruin, G.
In: J EUR ACAD DERMATOL, Vol. 33, No. 9, 09.2019, p. 1733-1741.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years
AU - Reich, K
AU - Blauvelt, A
AU - Armstrong, A
AU - Langley, R G
AU - de Vera, A
AU - Kolbinger, F
AU - Spindeldreher, S
AU - Ren, M
AU - Bruin, G
N1 - © 2019 European Academy of Dermatology and Venereology.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
U2 - 10.1111/jdv.15637
DO - 10.1111/jdv.15637
M3 - SCORING: Journal article
C2 - 31009130
VL - 33
SP - 1733
EP - 1741
JO - J EUR ACAD DERMATOL
JF - J EUR ACAD DERMATOL
SN - 0926-9959
IS - 9
ER -