Low Incidence of Antibodies to Recombinant Human Tissue-Type Plasminogen Activator in Treated Patients

Abstract

SummarySera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was a predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients’ serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.

Adverse Outcome of Early Recurrent Ischemic Stroke Secondary to Atrial Fibrillation after Repeated Systemic Thrombolysis

“…Animal models have demonstrated the formation of antibodies against rtPA [12, 13]. However, development of these antibodies in humans is unusual [14] and there are only occasional reports of IV rtPA-related anaphylactic reactions in “real-life” clinical practice [15]. Moreover, no anaphylactic reactions have been described among any of the 13 cases of repeated IV thrombolysis for ischemic stroke reported up to date (including ours).…”

Repeated Thrombolysis for Chronologically Separated Ischemic Strokes

“…5 Several studies investigated the development of antibodies against rt-PA after treatment for a variety of cardiac and noncardiac indications in humans. 3,4 Reed et al screened 1.686 patients after rt-PA administration and identified only 3 patients (Ͻ0.01%) who developed significant titers of antibodies. 3 Conversely, Cugno et al showed significantly increased titers in 14% of cardiac patients after treatment.…”

“…3,4 Reed et al screened 1.686 patients after rt-PA administration and identified only 3 patients (Ͻ0.01%) who developed significant titers of antibodies. 3 Conversely, Cugno et al showed significantly increased titers in 14% of cardiac patients after treatment. 4 Hence, the overall incidence of post-treatment antibodies against rt-PA is still unclear.…”

“…Development of antibodies against the recombinant protein has been described in various animal models 1,2 and humans. 3,4 However, their relevance for repeated application of the drug is unknown. 3,4 Antibodies may influence efficacy of repeated treatment by neutralizing the active drug and may even harm patients in case of allergic reactions because of sensitization.…”

“…3,4 However, their relevance for repeated application of the drug is unknown. 3,4 Antibodies may influence efficacy of repeated treatment by neutralizing the active drug and may even harm patients in case of allergic reactions because of sensitization. With many years since approval and an aging population, the question of efficacy and safety of repeated thrombolysis will gain importance.…”