Possibilities and Limitations in Substituting anti-Drug Antibody Titers with Signal-to-Noise Ratios: A Comprehensive Comparison Using Two Clinical Trial Datasets of Adalimumab.

Abstract

Immunogenicity assessment is vital in clinical trials and is measured through a multi-tiered approach (screening, confirmatory and titer assays). However, recent studies have suggested that titer results could be reported from ADA signal-to-noise ratios (S/N ratios=sample mean signal/negative control mean signal). More data analysis using two clinical trials of adalimumab: SB5-1003 (single-dose, healthy participants) and SB5-4001 (multiple-dose, interchangeability study, patients with plaque psoriasis), therefore, is indispensable whether substituting ADA S/N ratio as an alternative way of reporting titer results has no impact on interpretation on clinical outcome. In this study, we demonstrated that there is a strong correlation between S/N ratios and titers and no impact on overall PK results. Nonetheless, sub-analyses with time or adalimumab level showed a change in the regression between S/N ratios and titers, leading to different titer values from the same S/N ratio. These data demonstrate that S/N ratios may fully replace titers in limited circumstances such as a biosimilar study which goal is to prove equivalence between the originator and candidate product, but need a caution in other cases.