title: Time Course and Clinical Implications of Development of Antibodies Against Adalimumab in Patients With Inflammatory Bowel Disease.
abstract: Antibodies (Abs) against adalimumab (ADL) have been associated with low ADL levels and treatment failure.
  
  
  
  To characterize the temporal characteristics of anti-ADL Ab appearance and possible disappearance, and determine the clinical significance on drug efficacy and disease course.
  
  
  
  Cohort study including inflammatory bowel disease patients in whom anti-ADL Abs had been assessed by radioimmunoassay (RIA) and, in case of disappearance, by enzyme immunoassay, and functional reporter gene assay.
  
  
  
  Anti-ADL Abs were evaluated in 133 serum samples from 72 patients. Seventeen patients (24%) tested positive after median of 194 days, interquartile range of 66 to 361. The proportion with anti-ADL Abs was 22% after 1 year, and 32% from 21 months onwards. Anti-ADL Abs generally persisted at repeat assessments during continued ADL therapy (n=8). Disappearance of anti-ADL Abs during therapy (n=3) was presumably caused by methodological biases due to detection of nonfunctional nonpersistent anti-ADL Abs by RIA, or false-negative measurement at reassessment by RIA and reporter gene assay. Anti-ADL Abs appeared pharmacologically active as judged by a median ADL concentration below limit of detection versus 7.4 μg/mL in anti-ADL Ab-negative samples (P<0.0001). Anti-ADL Abs associated with loss of response (odds ratio estimated 67, P<0.0001), and shorter treatment duration (P<0.0001).
  
  
  
  Abs against ADL appear in approximately one fourth of inflammatory bowel disease patients with decreasing frequency over time and usually within 1 year of therapy. Anti-ADL Abs generally persist during continued ADL therapy, and are associated with elimination of drug and treatment failure. Therefore, ADL cessation should be considered when anti-ADL Abs are detected and supported by clinical observations.
authors.affiliation: *Department of Gastroenterology, Herlev Hospital, Herlev †Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Steenholdt
authors.forename: Madeline T
authors.initials: MT
authors.lastname: Frederiksen
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ainsworth
authors.forename: Ole Ø
authors.initials: OØ
authors.lastname: Thomsen
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
mesh_terms: D000068879:Adalimumab / Q000276:immunology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D000906:Antibodies / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D017930:Genes, Reporter; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D011863:Radioimmunoassay; D012189:Retrospective Studies; D013997:Time Factors; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000068879:Adalimumab