Abstract
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.