Reich, K, Blauvelt , A, Armstrong, A, Langley, R, de Vera, Ana, Kolbinger, Frank, Spindeldreher, Sebastian and Bruin, Gerardus (2019) Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years. Journal of the European Academy of Dermatology and Venereology.

Abstract

Introduction: Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL-17A, a key cytokine involved in psoriasis (PsO) and psoriatic arthritis (PsA) development, and has shown long lasting efficacy and safety in the complete spectrum of psoriasis manifestations. Monoclonal antibody therapies may be associated with the production of treatment-emergent anti-drug antibodies (TE-ADA) that can affect drug pharmacokinetics, diminish clinical responses, 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.
Material and Methods: Immunogenicity was evaluated up to Week 268 (5 years). TE-ADA were defined as positive anti-drug 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.
Conclusions: The yearly secukinumab immunogenicity incidence over 5 years of treatment was consistently below 1% in patients with moderate-to-severe plaque psoriasis. Any TE-ADA, including neutralizing antibodies, were not associated with loss of secukinumab efficacy or with clinical concerns.

Item Type:	Article
Date Deposited:	14 May 2019 00:45
Last Modified:	14 May 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38556