ArticleThe AAPS journal2022
Preclinical Observations of Systemic and Ocular Antidrug Antibody Response to Intravitreally Administered Drugs.
Article in The AAPS journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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0 citing papers in PubMed, 4 citations in OpenAlex.
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Intravitreally administered biotherapeutics can elicit local and systemic immune responses with potentially serious clinical consequences. However, little is known about the mechanisms of ocular antidrug immune response, the incidence of ocular antidrug antibodies (ADAs), and the relationship between ocular and systemic ADA levels. Bioanalytical limitations and poor availability of ocular matrices make studies of ocular immunogenicity particularly challenging. We have recently reported a novel bioanalytical ADA assay and shown its applicability for the ADA detection in ocular matrices. In the present study, we used this assay to analyze a large set of preclinical samples from minipig and cynomolgus monkeys treated with different ocular biotherapeutics. We found a significant association between the incidence of ADAs in plasma and ocular fluids after a single intravitreal administration of the drugs. Importantly, none of the animals with ADA-negative results in plasma had detectable ADAs in ocular fluids and systemic ADA response always preceded the appearance of ocular ADAs. Overall, our results suggest the systemic origin of ocular ADAs and support the use of plasma as a surrogate matrix for the detection of ocular ADA response.
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