Use of the tumor necrosis factor-blockers for Crohn's disease

Table 11 Mechanisms which are speculated to be the cause of primary non-response

Lack of response may be due to different immunoinflammatory mechanism(s)[63]

A differential role of TNFα in certain stages of disease

Individual differences in drug metabolism and elimination, drug binding in serum or tissues based on disease activity level[27,148]

The presence of innate anti-TNFα antibodies that may exhibit greater neutralizing activity in non-responders[175]

Absence of inflammation accounting for clinical symptoms

Unidentified, genetic or pharmacogenetic or serological backgrounds of individual patients[24,176-179]

Individual differences in bioavailability and pharmacokinetics, leading to inadequate concentrations of a biologic secondary to immunogenicity (neutralizing or non-neutralizing antibodies, or unmeasured or unknown antibody) or other factors that increase drug clearance (decreased circulation half -life and possible high consumption in severe disease)[27,128]

TNFα: Tumor necrosis factor-α.