An examination of the mechanisms involved in secondary clinical failure to adalimumab or etanercept in inflammatory arthropathies

J Clin Rheumatol. 2015 Apr;21(3):115-9. doi: 10.1097/RHU.0000000000000229.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / immunology*
  • Adalimumab / therapeutic use*
  • Adult
  • Aged
  • Antibodies / blood
  • Antibodies / immunology*
  • Antirheumatic Agents / immunology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Psoriatic / blood
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Psoriatic / immunology
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Etanercept / immunology*
  • Etanercept / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunogenetics
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antibodies
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Adalimumab
  • Etanercept