Human antichimeric antibody responses

Re-administration might be an issue for abciximab, due to its inherent immunogenicity. Human antichimeric antibody is detectable in about 5% to 6% patients receiving abciximab therapy, but no antibodies have been observed in response to the small molecules. In practice, re-administration registry of 500 patients showed similar safety and efficacy for repeat administration when compared with first time administration (80). No reports of hypersensitivity or anaphylactic reactions were reported with abciximab re-administration. Thus, these agents can be safely re-administered with careful monitoring of platelet counts, especially with abciximab therapy. 

Treatment with infliximab can be associated with the formation of human antichimeric antibodies. Such antibodies were rarely detected in patients with rheumatoid arthritis who were also taking methotrexate, and low titers were detected in about 13% of patients with Crohn s disease. Their clinical relevance is unclear, although their presence has sometimes been associated with an increased risk of infusion reactions, the occurrence of serum sickness-like reactions after delayed re-treatment, and a shorter duration of response. 

The clinical significance of antibodies to infliximab has also been explored in 125 patients with Crohn s disease who were given infliximab, of whom 61% had antibodies after the fifth infusion however, there was no further increase in incidence after subsequent treatment (21). The presence of antibodies was associated with a 2.4-fold increase in the risk of infusion reactions, lower serum infliximab concentrations, and a shorter duration of clinical response, compared with patients with no infliximab antibodies. Patients who received concomitant immunosuppressive therapy had a lower incidence of infliximab antibodies, higher infliximab serum concentrations, and a longer duration of clinical response. Pretreatment with glucocorticoids may reduce the risk of antibody formation, but it is not known whether a pretreatment test for human antichimeric antibodies has a predictive value for adverse reactions (22). However, there were technical issues relating to the antibody assay and definition of clinically relevant antibody titers in this study. 

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