Clinical Relevance of Immunoresistance to Botulinum Therapy

Because botulinum toxin is a bacterial antigen, the therapy with this biological bears the risk that the formation of antibodies is elicited which can neutralize the neurotoxin. Several factors have an impact on this immune response. There are (unknown) patientrelated factors but also the dose, the injection interval and the purity of the product play a role in the formation of antibodies. Several assays to detect antibodies are available; immunological assays such as FIA (fluorescence immunoassay) and ELISA, function assays such as MPA (mouse protection assay) and HDA (hemidiaphragm assay), clinical assays such as the EDB assay (extensor digitorum brevis assay), and SCM assay (sternocleidomastoid) which have different sensitivities. Clinical studies with different BoNT/A products demonstrate that the rate of antibody formation is low. Important for the physician is whether the antibody formation has an impact on the responsiveness of the patient. Not all patients with positive sera are nonresponders. The antibody titer is certainly important which might not be high enough to neutralize the injected dose completely but the titer might increase during further treatment with the neurotoxin leading to complete nonresponse. To avoid the formation of antibodies, the lowest dose necessary for the patient should be injected keeping the longest acceptable injection interval.