title: Review article: Causative factors and the clinical management of patients with Crohn's disease who lose response to anti-TNF-α therapy.
abstract: BACKGROUND
  The addition of antitumour necrosis factor-α (TNF-α) agents to the therapeutic armamentarium against Crohn's disease has been a revolution in its management. However, approximately 25 to 40% of patients who initially benefit from anti-TNF-α treatment develop intolerable adverse events or lose their response during maintenance therapy.
  
  
  OBJECTIVE
  To summarise the current knowledge on the mechanisms underlying loss of response in these patients and the therapeutic strategies available to counteract this clinical challenge.
  
  
  METHODS
  A literature search using PubMed, MedLine and Embase databases has been performed.
  
  
  RESULTS
  Anti-infliximab antibodies formation and autoantibodies (ANA, anti-DNA and other autoantibodies) have been associated with loss of response. Individual differences in drug metabolism may contribute to loss of response. Smoking may be a risk factor for loss of response. Dose escalation, reduction of infusion intervals and switch to other anti-TNF-α agents are effective as rescue strategies.
  
  
  CONCLUSIONS
  Loss of response appears to result from different causes not fully established by now. Optimization of therapies, or switch to other anti-TNF-α, are currently the best studied strategies in case of loss of response, and can be successful in 40-60% of patients who lose response.
authors.affiliation: IBD Unit, IBD Center, Division of Gastroenterology, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Danese
authors.forename: G
authors.initials: G
authors.lastname: Fiorino
authors.forename: W
authors.initials: W
authors.lastname: Reinisch
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D000069285:Infliximab; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab