title: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis.
abstract: BACKGROUND
  The proinflammatory cytokine interleukin (IL)-17A plays a pivotal role in psoriasis pathogenesis. Secukinumab, a fully human monoclonal antibody (mAb) that selectively targets IL-17A, has been demonstrated to be highly efficacious for the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favourable safety profile. mAb therapies may be associated with production of antidrug antibodies (ADAs) that can affect drug pharmacokinetics, diminish response or cause hypersensitivity reactions.
  
  
  OBJECTIVE
  To investigate the immunogenicity of secukinumab across six phase III clinical trials in which patients with plaque psoriasis were treated with secukinumab for up to 52 weeks and additionally followed up at week 60.
  
  
  METHODS
  Immunogenicity in patients with plaque psoriasis exposed to secukinumab was evaluated at baseline and at weeks 12, 24, 52 and 60. Treatment-emergent (TE)-ADAs were defined as a positive ADA signal detected in post-treatment samples from patients with a negative baseline signal. Confirmed positive samples were further analysed for their drug-neutralizing potential.
  
  
  RESULTS
  Among 2842 patients receiving secukinumab and evaluated for ADAs, 11 (0·4%) developed TE-ADAs. Associations between TE-ADAs and secukinumab dose, frequency or mode of administration were not observed. Neutralizing antibodies were detected in three of nine evaluable patients with TE-ADAs.
  
  
  CONCLUSIONS
  Secukinumab immunogenicity was low, as shown by TE-ADA detection in only 11 of 2842 (0·4%) patients with moderate-to-severe plaque psoriasis treated with secukinumab. All but one of the patients with TE-ADAs were biologic naive. Neither TE-ADAs nor neutralizing antibodies were associated with loss of secukinumab efficacy or issues of clinical concern.
authors: Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany.
authors: K
authors: K
authors: Reich
authors: Oregon Medical Research Center, Portland, OR, U.S.A.
authors: A
authors: A
authors: Blauvelt
authors: University of Southern California, Los Angeles, CA, U.S.A.
authors: A
authors: A
authors: Armstrong
authors: Dalhousie University, Halifax, NS, Canada.
authors: R G
authors: RG
authors: Langley
authors: Novartis Pharma AG, Basel, Switzerland.
authors: T
authors: T
authors: Fox
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A.
authors: J
authors: J
authors: Huang
authors: Novartis Pharma AG, Basel, Switzerland.
authors: C
authors: C
authors: Papavassilis
authors: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors: E
authors: E
authors: Liang
authors: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors: P
authors: P
authors: Lloyd
authors: Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors: G
authors: G
authors: Bruin
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D003879:Dermatologic Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D003879:Dermatologic Agents; C508717:IL17A protein, human; D020381:Interleukin-17; C555450:secukinumab