title: Review article: immunogenicity of anti-TNF biologics in IBD - the role of patient, product and prescriber factors.
abstract: BACKGROUND
  Anti-drug antibodies (ADAs) to biologic therapies contribute to the loss of response and infusion reactions to anti-TNF drugs in patients with inflammatory bowel disease (IBD). The reasons behind this immunogenicity are complex, and have not been the focus of a dedicated review for prescribers.
  
  
  OBJECTIVE
  To provide an overview of the patient, product and prescriber factors, which have been associated with the immunogenicity of anti-TNF therapy, and draw conclusions for clinical practice.
  
  
  METHODS
  Review of representative observational studies and clinical trials from the IBD and other literature, which report associations with ADA development, with a focus on infliximab and adalimumab.
  
  
  RESULTS
  ADAs develop in 10-20% of patients receiving anti-TNF maintenance therapy, and these patients are three times more likely to lose response as ADA-negative patients. Patient genotype plays a role in ADA risk in a minority of patients, but age or disease type is not a major factor. Drug mishandling, such as agitation or freeze-thaw cycles, can induce protein aggregates, which are known to be immunogenic. Prescription of maintenance therapy with concomitant immunomodulators, and achieving suitable trough drug levels, reduces the risk of ADAs in patients with IBD.
  
  
  CONCLUSIONS
  Patients and prescribers can take several steps to reduce the risk of development of anti-drug antibodies to anti-TNF antibodies. Further research is required to determine if immunogenic factors identified in other situations apply to use of anti-TNFs in IBD.
authors.affiliation: Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Moss
authors.forename: V
authors.initials: V
authors.lastname: Brinks
authors.forename: J F
authors.initials: JF
authors.lastname: Carpenter
mesh_terms: D000068879:Adalimumab; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D000069285:Infliximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab