title: Immunogenicity, adalimumab levels and clinical response in ankylosing spondylitis patients during 24 weeks of follow-up.
abstract: BACKGROUND
  Immunogenicity influences adalimumab levels and therefore clinical response in patients with rheumatic diseases.
  
  
  OBJECTIVE
  To study the relationship between clinical response, adalimumab levels and antidrug antibodies (ADAb) in ankylosing spondylitis (AS).
  
  
  METHODS
  Observational cohort study of 115 consecutive AS patients treated with adalimumab in the Netherlands (n=85) and Taiwan (n=30), monitored during 24 weeks. Adalimumab levels and ADAb titres were determined using an ELISA and an antigen binding test (ABT), respectively, designed by Sanquin Research, Amsterdam. Response to adalimumab treatment was defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) response, and disease activity was measured using the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (CRP) (ASDAS).
  
  
  RESULTS
  At baseline, median BASDAI (IQR) was 6.4 (4.5-7.6) and mean ASDAS (SD) was 3.5 (1.0). After 24 weeks, 49 (42.6%) patients were BASDAI50 responders and mean ASDAS (SD) for responders was 1.5 (1.0) vs 2.6 (1.0) for non-responders (p<0.001). Thirty-one (27.0%) patients had detectable ADAb. After 24 weeks, adalimumab levels (mg/L) (IQR) were significantly higher in ADAb-negative patients than in ADAb-positive patients (12.7 (8.2-18.0) vs 1.2 (0.0-2.0), (p<0.001)). A significant association was demonstrated between adalimumab levels and ASDAS (p=0.02; RC -1.1; 95% CI -2.0 to -0.2). Eleven (9.6%) patients had no detectable adalimumab levels and high detectable ADAb titres (>100 AU/mL). In these patients, CRP and erythrocyte sedimentation rate remained elevated during treatment.
  
  
  CONCLUSIONS
  Adalimumab levels are related to clinical response in AS patients measured with ASDAS and are influenced by ADAb detectable with an ABT.
authors: Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands.
authors: Eva L
authors: EL
authors: Kneepkens
authors: Departments of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: James Cheng-Chung
authors: JC
authors: Wei
authors: Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors: Michael T
authors: MT
authors: Nurmohamed
authors: Departments of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Kai-Jieh
authors: KJ
authors: Yeo
authors: Departments of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: C Y
authors: CY
authors: Chen
authors: Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors: Irene E
authors: IE
authors: van der Horst-Bruinsma
authors: Laboratory for Monoclonal Therapeutics, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors: Desiree
authors: D
authors: van der Kleij
authors: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors: Theo
authors: T
authors: Rispens
authors: Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors: Gertjan
authors: G
authors: Wolbink
authors: Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands.
authors: Charlotte L M
authors: CL
authors: Krieckaert
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000906:Antibodies / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000276:immunology* / Q000627:therapeutic use*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab
keywords: Ankylosing Spondylitis; Anti-TNF; Pharmacokinetics; Spondyloarthritis; TNF-alpha