Drug-neutralizing Antibodies against TNF-α blockers as Biomarkers of Therapy Effect Evaluation

Folia Med (Plovdiv). 2020 Jun 30;62(2):282-289. doi: 10.3897/folmed.62.e39402.

Abstract

Introduction: TNF-α blocker therapy is part of the treatment with biologics used in the management of inflammatory joint diseases. In recent years, drug-induced neutralizing antibodies have been shown to have a negative effect on the course of the disease process.

Aim: To investigate drug-induced neutralizing antibodies against TNF-α blocking drugs used in patients with inflammatory joint diseases and their effect on the clinical course of the disease.

Materials and methods: The study included 121 (56.8%) patients with rheumatoid arthritis, 50 (23.5%) patients with ankylosing spondylitis, 42 (19.7%) patients with psoriatic arthritis, and 31 sex and age-matched healthy controls. The patients were monitored at 0, 6, 12, and 24 months after initiation of TNF-α blocker treatment. The demographic data, vital signs and the parameters of inflammatory activity (C-reactive protein, erythrocyte sedimentation rate, and disease activity indices) were analyzed in all patients. Drug-induced anti-TNF-α blockers antibodies (adalimumab and etanercept) were analyzed using ELISA. Statistical analysis was performed with SPSS v. 24.

Results: Drug-induced neutralizing antibodies against adalimumab were obtained in 11.57% of patients at 6 month, in 17.64% at 12 month, and in 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not demonstrated in patients followed up at 6 months, at 7.77% at 12 months, and at 9.63% at 24 months. Between the presence of neutralizing antibodies to blockers of TNF-α and indices available for disease activity, there is a strong positive correlation and Pearson Correlation = 0.701, p=0.001. Patients with poor clinical response and available antibodies against adalimumab at 12 months were 82.36% and patients treated with etanercept 71.42%. The difference between the two groups was non-significant (U = 0.527, p> 0.05). Patients with poor clinical response and available anti-adalimumab antibodies at 24 month were 75%, and in patients treated with etanercept - 87.50%, the difference between the two groups not being able to reach significance (U = 0.623, p> 0.05).

Conclusion: Drug-induced neutralizing antibodies against TNF-α blockers (adalimumab and etanercept) have a negative effect on the course of inflammatory joint disease and can be used as reliable biomarker to assess the effect of the treatment with these drugs.

Keywords: TNF-α blockers; biomarkers; inflammatory joint disease.

MeSH terms

  • Adalimumab / immunology
  • Adalimumab / therapeutic use
  • Adult
  • Aged
  • Antibodies, Neutralizing / immunology*
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Psoriatic / metabolism
  • Arthritis, Psoriatic / physiopathology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Etanercept / immunology
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / physiopathology
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / immunology*
  • Tumor Necrosis Factor Inhibitors / therapeutic use*
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Tumor Necrosis Factor Inhibitors
  • C-Reactive Protein
  • Adalimumab
  • Etanercept