title: Long-term measurement of anti-adalimumab using pH-shift-anti-idiotype antigen binding test shows predictive value and transient antibody formation.
abstract: OBJECTIVE
  Therapeutic monoclonal antibodies are effective drugs for many different diseases. However, the formation of anti-drug antibodies (ADA) against a biological can result in reduced clinical response in some patients. Measurement of ADA in the presence of (high) drug levels is difficult due to drug interference in most assays, including the commonly used antigen binding test (ABT).
  
  
  METHODS
  We recently published a novel method which enables the measurement of complexed antibodies against adalimumab (an anti-TNF antibody) in the presence of drug. Here we use this pH-shift-anti-idiotype ABT (PIA) to measure anti-adalimumab antibodies (AAA) in 99 rheumatoid arthritis (RA) patients treated for up to 3 years with adalimumab.
  
  
  RESULTS
  53 out of 99 RA patients produced AAA. In 50 of these PIA positive patients, AAA could be detected within the first 28 weeks of treatment. Patients in which AAA could be detected in the PIA after 28 weeks of treatment were more prone to declining adalimumab levels (<5 µg/ml) (p<0.01) and high AAA levels which could be detected in the ABT (p<0.05) at later time points. We observed transient AAA formation in 17/53 patients.
  
  
  CONCLUSIONS
  Results show that AAA develop early in treatment. However, levels that completely neutralise the drug may be reached much later in treatment. Furthermore, the patients positive for PIA at 28 weeks have an increased chance to develop clinical non-response due to immunogenicity. In some of the patients, AAA formation is transient.
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Pauline A
authors.initials: PA
authors.lastname: van Schouwenburg
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Krieckaert
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
authors.forename: Lucien
authors.initials: L
authors.lastname: Aarden
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Wolbink
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D000917:Antibody Formation; D018501:Antirheumatic Agents / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012720:Severity of Illness Index; D017211:Treatment Failure
chemical_list: D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab