Corresponding author: Krasimir Kraev ( kkraev@hotmail.com ) Corresponding author: Mariela Geneva-Popova ( genevapopova@yahoo.com ) © Krasimir Kraev, Mariela Geneva-Popova, Velichka Popova, Stanislava Popova, Ana Maneva, Anastas Batalov, Teodora Stankova, Ginka Delcheva, Katya Stefanova. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation:
Kraev K, Geneva-Popova M, Popova V, Popova S, Maneva A, Batalov A, Stankova T, Delcheva G, Stefanova K (2020) Drug-neutralizing Antibodies against TNF-α blockers as Biomarkers of Therapy Effect Evaluation. Folia Medica 62(2): 282-289. https://doi.org/10.3897/folmed.62.e39402 |
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.