The combination of an anti-TNF alpha and methotrexate may also prevent the development of antibodies to anti TNF alpha. Observational studies indicated that MTX dose-dependently inhibits the development of anti-drug antibodies and could reduce the accelerated clearance of biological agents associated with loss of therapeutic response in inflammatory diseases. Reduced ADA development influence positively clinical response and therefore likely drug maintenance through optimizations of drug pharmacokinetics and serum anti TNF alpha trough concentrations.