Secukinumab exhibits low immunogenicity during 104 weeks of treatment in subjects with moderate to severe plaque psoriasis.

Abstract

Introduction: Secukinumab is a fully Human monoclonal antibody that selectively Targets IL-17A for the treatment of Psoriasis. Biological drugs can induce anti-bodies (ADA) that may affect pharmacokinetics, diminish response, or cause hypersensitivity. Here, in a 4- year extension of two phase 3 studies ERASURE and FIXTURE, we evaluated the immunogenicity of secukinumab at Wk104 of treatment. Methods: Subjects completing either core study with at least a partial response (PASI >50) to secukinumab at Wk52 were eligible for inclusion. PASI 75 responders in each secukinumab dose group of the core studies were randomized 2:1 to continue the same doses of secukinumab (300mg or 150 mg) or receive placebo (300mg-PBO or 150mg-PBO) every 4 weeks. Blood samples obtained at Wk52, Wk76 and Wk104 were assayed for treatment-emergent ADA (TE- ADA). Confirmed TE- ADA samples were analysed for neutralizing potential. Results: Te-ADA were detected in 6/1142 (0.53%) subjects tested; one in the 300mg arm, three in the 150mg arm, and two in the 150mg-PBO arm. Two subjects, one each in the 300mg and 150mg-PBO treatment groups, tested positive for neutralizing antibodies at Wk76, Among the six subjects with TE-ADA, four later reverted to a seronegative state during therapy, TE-ADA, including in the 2 subjects with neutralizing antibodies, were not associated with loss of response of hypersensitivity reactions. Conclusion: TE-ADA and neutralizing antibodies were reported rarely with secukinumab treatment out to 2 years, and were not associated with loss of secukinumab efficacy or other issues of clinical concern.