Since the approval of the first anti-tumor necrosis factor (anti-TNF) therapy in late 1998, the treatment for Crohn's disease (CD) has been revolutionized. Anti-TNF therapy has been consistently shown in numerous clinical trials to be effective for patients with more aggressive perianal, internal penetrating, and fistulizing CD. However, the loss of clinical remission is frequent and only one-third of patients remain in clinical remission at 1 year. The pharmacokinetics of anti-TNF is highly variable among patients and could be influenced by many factors including serum albumin, gender, body weight, systemic inflammation and route of administration. The main factor impacting anti-TNF pharmacokinetics and efficacy is the development of immunogenicity where antidrug antibodies accelerate anti-TNF drug clearance. In this review paper, we evaluate the role of combination therapy with anti-TNF drugs and immunomodulators, the role of therapeutic drug monitoring, and strategies to recapture loss of clinical response in order to improve both short- and long-term outcomes in CD patients.
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