Ex vivo comparative immunogenicity assessment (EVCIA) to determine relative immunogenicity in chronic plaque psoriasis in participants receiving Humira® or undergoing repeated switches between Humira® and AVT02

• Published in: Immunotherapy advances Vol. 4; no. 1; p. ltad029
• Main Authors: Richter, Kathleen, Haliduola, Halimu N, Schockaert, Jana, Mazy, Aurélie, Reznichenko, Nataliya, Guenzi, Eric, Berti, Fausto
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 01.01.2024
• Subjects: cellular immunogenicity; comparative immunogenicity assessment (EVCIA); AVT02; adalimumab biosimilar; humoral response; Ex vivo comparative immunogenicity assessment (EVCIA)
• ISSN: 2732-4303; 2732-4303
• DOI: 10.1093/immadv/ltad029

Summary Immunogenicity against biologic medicines is ubiquitous, and it is traditionally measured by the final humoral response. However, the onset of a sustained immunogenic response begins at the cellular level with activation of T cells and maturation of naïve B cells into plasma cells. Ex vivo comparative immunogenicity assessment (EVCIA) of cellular immunogenicity in participants with moderate-to-severe chronic plaque psoriasis in the AVT02-GL-302 study, who received either reference product (RP) alone (non-switching arm) or switched between RP and AVT02 (switching arm) after 1:1 randomization at week 12. Peripheral blood mononuclear cells (PBMCs) were collected and cryopreserved from 28 participants at: baseline (before treatment) (week 1); pre-randomization (week 12); and week 16 and week 28 in both switching and non-switching arms. PBMCs were thawed and re-exposed to either medium alone (negative control), RP, AVT02, keyhole limpet hemocyanin (KLH) (positive control), RP+KLH, or AVT02+KLH. Samples from 10 participants (predetermined average cell viability of 75% across all timepoints) from each arm were analyzed for cytokine release after 24 hours and for Th-cell proliferation, 6 days post-seeding. Until week 28, cytokine release and Th-cell proliferation was similar at all time points in both switching and non-switching arms. Overall cellular immune response was elevated post-KLH re-exposure at all timepoints. The comparable ex vivo cellular immunogenicity between switching and non-switching arms complements the confirmation of interchangeability in the main study. Given the sensitivity of novel EVCIA, detecting cellular immunogenicity could be a potential outcome in predicting the immunogenicity of biologic medicines. Graphical Abstract Graphical Abstract