Comparing anti-drug antibody signal-to-noise ratios to assess immunogenicity and interchangeability in adalimumab biosimilar studies

Abstract

ABSTRACT Background To support an interchangeability designation for Sandoz adalimumab biosimilar (GP2017), antidrug antibody (ADA) signal-to-noise (S/N) ratios were assessed in the GP2017 ADACCESS trial to directly assess potential changes in immunogenicity. Research design and methods ADACCESS was a 51-week trial in patients with moderate-to-severe plaque psoriasis that included patients treated continuously with reference adalimumab (cH), and patients who experienced four switches between reference adalimumab and GP2017 (H2H). ADAs were measured every 6 weeks during the switching phase using an electrochemiluminescence assay. A non-parametric analysis was performed to estimate the 90% confidence interval (CI) of the median of difference in ADA S/N ratios between the cH and H2H treatment groups at week 41. If the 90% CI was within the margin of –0.16 to 0.16 (representing assay noise), this was considered a non-clinically meaningful difference in immunogenicity. Results The 90% CIs of the median of difference in ADA S/N ratios between the two treatment groups were within the defined margin of –0.16 to 0.16 at week 41, and at all other time points. Efficacy and safety data were also similar between the treatment groups. Conclusion Analysis of ADA S/N ratios showed no increase in immunogenicity following up to four switches between reference adalimumab and GP2017. Trial registration NCT02016105