The present invention provides assays for detecting and measuring the presence or level of autoantibodies to anti-TNFalpha drug therapeutics in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFalpha drug therapeutics to detect the presence or level of autoantibodies against the drug. The present invention also provides methods for selecting therapy, optimizing therapy, and/or reducing toxicity in subjects receiving anti-TNFalpha drugs for the treatment of TNFalpha-mediated disease or disorders.