Impact of Repeated Antigen Exposure on Humoral Tolerance: Antidrug Antibodies After Single-Dose Versus Multi-dose Adalimumab.

Authors

Anika M Valk, Jolinde van Strien, Ninotska Derksen, Dorien Kos, Júlia Castellon Teixell, Jerry Janssen, Floris C Loeff, Lisanne Dijk, Maureen Leeuw, Catherine Smith, Teresa Tsakok, Richard Warren, Nick J Reynolds, Christopher E M Griffiths, Jonathan Barker, BSTOP Study Group, PSORT Consortium, Robert Rissman, Wouter Ten Voorde, Justin Jacobse, Daniel Alvarez, Marieke van Ham, Gertjan Wolbink, Anja Ten Brinke, Theo Rispens

Published in

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. Jun 17, 2026. Epub Jun 17, 2026.

Abstract

Therapeutic proteins such as adalimumab can elicit an antibody response. How dosing regimens impact immunogenicity remains ill-understood, especially with respect to the frequency of dosing.
We aimed to investigate the relationship between single versus multiple adalimumab doses and immunogenicity, in terms of anti-drug antibody production and skewing towards the non-inflammatory immunoglobulin G4 (IgG4) subclass.
Immunoglobulin M, immunoglobulin G, and IgG4 anti-drug antibodies were analyzed in retrospective cohorts of healthy individuals and patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, or psoriasis, receiving one or multiple doses of adalimumab, using optimized drug-tolerant assays, newly developed in the case of IgG4.
A single dose of adalimumab proved highly immunogenic, while repeated dosing, resulting in prolonged exposure to high antigen concentrations, led to attenuation of the anti-drug antibody response. Immunoglobulin G4 anti-drug antibodies developed earlier than previously reported with drug-sensitive assays, appearing as early as week 3, even after a single dose of adalimumab. Skewing towards IgG4 was nevertheless stronger with repeated dosing.
Repeated high-dose adalimumab exposure can limit both the magnitude and inflammatory potential of the antibody response. These results highlight drug exposure as a factor modulating the immunogenicity of biologics.

PMID:
42307860
Bibliographic data and abstract were imported from PubMed on 17 Jun 2026.

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