The present disclosure relates to methods of reducing accelerated blood clearance of at least one pegylated therapeutic composition in a subject suffering from a disease and in need of treatment. The methods involve administering at least one high molecular weight polyethylene glycol composition to a subject suffering from a disease. The administration of at least one high molecular weight polyethylene glycol composition can also be used to increase the circulation half-life of at least one pegylated therapeutic composition as well as restore the pharmacokinetics of the pegylated therapeutic composition in a subject having a high titer of anti-polyethylene glycol antibodies.
