Cargando…
Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab
INTRODUCTION: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy in the treatment of moderate to severe plaque psoriasis (PsO) and psoriatic arthritis (PsA), demonstrating a rapid onset of action and sustained responses wit...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Healthcare
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825325/ https://www.ncbi.nlm.nih.gov/pubmed/29392570 http://dx.doi.org/10.1007/s13555-018-0220-y |
_version_ | 1783302172367126528 |
---|---|
author | Spindeldreher, Sebastian Maillère, Bernard Correia, Evelyne Tenon, Maxime Karle, Anette Jarvis, Philip Kolbinger, Frank |
author_facet | Spindeldreher, Sebastian Maillère, Bernard Correia, Evelyne Tenon, Maxime Karle, Anette Jarvis, Philip Kolbinger, Frank |
author_sort | Spindeldreher, Sebastian |
collection | PubMed |
description | INTRODUCTION: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy in the treatment of moderate to severe plaque psoriasis (PsO) and psoriatic arthritis (PsA), demonstrating a rapid onset of action and sustained responses with a favorable safety profile. All biotherapeutics, including monoclonal antibodies (mAbs), can be immunogenic, leading to formation of anti-drug antibodies (ADAs) that can result in loss of response and adverse events such as hypersensitivity reactions. Thus, the immunogenicity potential of biotherapeutics is of particular interest for physicians. Of the 2842 patients receiving secukinumab across six phase 3 psoriasis clinical trials, only 0.4% developed treatment-emergent ADAs over 3 years of treatment. Direct comparison of clinical immunogenicity incidence rates is hampered by the nature of clinical immunogenicity assays, differences in study designs, patient populations, and treatment regimens. METHODS: We evaluated side-by-side in the same healthy donors two recently approved IL-17A selective antibodies, secukinumab and ixekizumab, along with adalimumab and ustekinumab, for their capacity to induce anti-drug related T cell responses in vitro and estimated their potential for developing ADAs in patients. RESULTS: We found that healthy donors show both significantly less frequent T cell responses and lower numbers of pre-existing T cells to secukinumab than to ixekizumab and adalimumab. Although there was a tendency for a lower response to ustekinumab, this difference was not significant. CONCLUSION: In summary, this in vitro study confirms the significantly lower immunogenicity potential and provides an explanation for the lower clinical immunogenicity incidence found for secukinumab in comparison to other approved therapeutic antibodies used to treat plaque psoriasis. FUNDING: Novartis Pharmaceuticals AG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13555-018-0220-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5825325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-58253252018-02-28 Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab Spindeldreher, Sebastian Maillère, Bernard Correia, Evelyne Tenon, Maxime Karle, Anette Jarvis, Philip Kolbinger, Frank Dermatol Ther (Heidelb) Original Research INTRODUCTION: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy in the treatment of moderate to severe plaque psoriasis (PsO) and psoriatic arthritis (PsA), demonstrating a rapid onset of action and sustained responses with a favorable safety profile. All biotherapeutics, including monoclonal antibodies (mAbs), can be immunogenic, leading to formation of anti-drug antibodies (ADAs) that can result in loss of response and adverse events such as hypersensitivity reactions. Thus, the immunogenicity potential of biotherapeutics is of particular interest for physicians. Of the 2842 patients receiving secukinumab across six phase 3 psoriasis clinical trials, only 0.4% developed treatment-emergent ADAs over 3 years of treatment. Direct comparison of clinical immunogenicity incidence rates is hampered by the nature of clinical immunogenicity assays, differences in study designs, patient populations, and treatment regimens. METHODS: We evaluated side-by-side in the same healthy donors two recently approved IL-17A selective antibodies, secukinumab and ixekizumab, along with adalimumab and ustekinumab, for their capacity to induce anti-drug related T cell responses in vitro and estimated their potential for developing ADAs in patients. RESULTS: We found that healthy donors show both significantly less frequent T cell responses and lower numbers of pre-existing T cells to secukinumab than to ixekizumab and adalimumab. Although there was a tendency for a lower response to ustekinumab, this difference was not significant. CONCLUSION: In summary, this in vitro study confirms the significantly lower immunogenicity potential and provides an explanation for the lower clinical immunogenicity incidence found for secukinumab in comparison to other approved therapeutic antibodies used to treat plaque psoriasis. FUNDING: Novartis Pharmaceuticals AG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13555-018-0220-y) contains supplementary material, which is available to authorized users. Springer Healthcare 2018-02-01 /pmc/articles/PMC5825325/ /pubmed/29392570 http://dx.doi.org/10.1007/s13555-018-0220-y Text en © The Author(s) 2018 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Spindeldreher, Sebastian Maillère, Bernard Correia, Evelyne Tenon, Maxime Karle, Anette Jarvis, Philip Kolbinger, Frank Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab |
title | Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab |
title_full | Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab |
title_fullStr | Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab |
title_full_unstemmed | Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab |
title_short | Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab |
title_sort | secukinumab demonstrates significantly lower immunogenicity potential compared to ixekizumab |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825325/ https://www.ncbi.nlm.nih.gov/pubmed/29392570 http://dx.doi.org/10.1007/s13555-018-0220-y |
work_keys_str_mv | AT spindeldrehersebastian secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab AT maillerebernard secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab AT correiaevelyne secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab AT tenonmaxime secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab AT karleanette secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab AT jarvisphilip secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab AT kolbingerfrank secukinumabdemonstratessignificantlylowerimmunogenicitypotentialcomparedtoixekizumab |