title: An examination of the mechanisms involved in secondary clinical failure to adalimumab or etanercept in inflammatory arthropathies.
abstract: BACKGROUND
  Biological therapies against tumor necrosis factor α have revolutionized the treatment of several inflammatory rheumatic diseases. However, 30% of responders will present a clinical failure after having controlled the disease for at least 6 months (secondary clinical failure). Biological therapies may induce an unwanted immune response, which may alter the bioavailability of the drug causing a loss of clinical response.
  
  
  OBJECTIVE
  The objective of this study was to assess the correlation between secondary clinical failure (based on Disease Activity Score in 28 Joints or Bath Ankylosing Spondylitis Disease Activity Index) and the type of mechanism involved in failure (based on drug levels) in patients with inflammatory arthropathies treated with anti-tumor necrosis factor α.
  
  
  METHODS
  Drug and antidrug antibodies (ADAs) serum levels were determined by enzyme-linked immunosorbent assay immediately before drug administration in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis who presented secondary clinical failure after at least 6 months of treatment with adalimumab (ADL) or etanercept (ETN).
  
  
  RESULTS
  Thirty-six patients with secondary clinical failure were recruited: 63.88% had rheumatoid arthritis, 22.22% had psoriatic arthritis, and 13.88% had ankylosing spondylitis; 58.33% did not respond to ADL, whereas 41.66% did not to ETN. None of the patients treated with ETN showed either subtherapeutic drugs levels or ADAs (failure due to a primary mechanism) whereas it was found that 23.80% of the patients treated with ADL had subtherapeutic drug levels for reasons attributable to immunogenicity (failure due to a secondary mechanism; P = 0.000048).
  
  
  CONCLUSIONS
  We suggest the utility of measuring drug and ADA levels in patients with secondary clinical failure to ADL for a better optimization and rational use, but not in patients who fail to ETN.
authors: From the *Department of Physiology, Faculty of Medicine, University of Granada; †Rheumatology Division, University Hospital "San Cecilio"; and ‡Rheumatology Division, University Hospital "Virgen de las Nieves," Granada, Spain.
authors: Sara
authors: S
authors: Bandrés Ciga
authors: Juan
authors: J
authors: Salvatierra
authors: Mar
authors: M
authors: López-Sidro
authors: Antonio
authors: A
authors: García-Sánchez
authors: Raquel
authors: R
authors: Durán
authors: Francisco
authors: F
authors: Vives
authors: Enrique
authors: E
authors: Raya-Álvarez
mesh_terms: D000068879:Adalimumab / Q000276:immunology* / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D018501:Antirheumatic Agents / Q000276:immunology / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007125:Immunogenetics; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept