Immunogenicity of biologicals
Project leaders: Theo Rispens PhD, Gertjan Wolbink MD PhD, Diana Wouters PhD, Prof Marieke van Ham PhD, Steven Stapel PhD and Prof Lucien Aarden PhD
With over 20 therapeutic monoclonal antibodies (tmAb) registered and many more in development, an ever increasing number of patients is now exposed to these biologics, often for prolonged periods of time. Even in case the tmAb is fully human, anti-idiotypic responses are elicited in a considerable fraction of the patients. This leads to reduced efficacy due to blocking of the therapeutic drug by anti-drug antibodies (ADA). Moreover, patients may develop treatment related side effects due to the formation of immune complexes (IC).
We studied antibody formation in rheumatoid arthritis patients treated at 2-weekly intervals with the fully human anti-TNFα antibody adalimumab and found that within 6 months of treatment 70% of the patients produce anti-adalimumab antibodies, mostly of the IgG1 and IgG4 subclass. Small circulating IC can be detected in most patients even two weeks after administration of adalimumab. Therefore these patients are permanently exposed to high concentrations of small IC.
Key publications
- Van Schouwenburg PA, Bartelds GM, Hart MH, Aarden L, Wolbink GJ, Wouters DA. Novel method for the detection of antibodies to adalimumab in the presence of drug reveals “hidden” immunogenicity in rheumatoid arthritis patients. J Immunol Methods 2010; 362:82-88.
- Rispens T, van Leeuwen A, Vennegoor A, Killestein J, Aalberse RC, Wolbink GJ, Aarden LA. Measurement of serum levels of natalizumab, an immunoglobulin G4 therapeutic monoclonal antibody. Anal Biochem 2011; 411:271-76.
- Bartelds GM, Wijbrandts CA, Nurmohamed MT, Stapel S, Lems WF, Aarden L, Dijkmans BA, Tak PP, Wolbink GJ. Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study. Ann Rheum Dis 2010; 69:817-21.
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