Anti-Drug Antibodies, Drug Levels, Interleukin-6 and Soluble TNF Receptors in Rheumatoid Arthritis Patients during the First 6 Months of Treatment with Adalimumab or Infliximab: A Descriptive Cohort Study
Autor: | M Stoltenberg, Klaus Bendtzen, Else Marie Bartels, Grith Eng, Pierre Bouchelouche, Henning Bliddal |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Physiology Reporter Gene Assay lcsh:Medicine Arthritis Biochemistry Gastroenterology Receptors Tumor Necrosis Factor Arthritis Rheumatoid Cohort Studies 0302 clinical medicine Immune Physiology Medicine and Health Sciences lcsh:Science Innate Immune System Multidisciplinary biology Pharmaceutics Drugs Interleukin Middle Aged C-Reactive Proteins Rheumatoid arthritis Cytokines Female Research Article medicine.drug Adult medicine.medical_specialty Inflammatory Diseases Immunology Rheumatoid Arthritis Research and Analysis Methods Antibodies Autoimmune Diseases 03 medical and health sciences Pharmacotherapy Rheumatology Drug Therapy Internal medicine medicine Adalimumab Humans Molecular Biology Techniques Interleukin 6 Molecular Biology Pharmacology 030203 arthritis & rheumatology Molecular Biology Assays and Analysis Techniques Interleukin-6 Tumor Necrosis Factor-alpha business.industry lcsh:R Biology and Life Sciences Proteins Molecular Development medicine.disease Infliximab Methotrexate 030104 developmental biology Solubility Immune System Antibody Formation biology.protein Clinical Immunology lcsh:Q Clinical Medicine business Biomarkers Developmental Biology |
Zdroj: | PLoS ONE, Vol 11, Iss 9, p e0162316 (2016) PLoS ONE |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0162316 |
Popis: | Objectives With the present study we wanted to explore the impact of treatment with a tumor necrosis factor-α -inhibitor (TNFi) on levels of soluble biomarkers in rheumatoid arthritis (RA) patients and to identify predictors of impaired drug levels and development of anti-TNFi antibodies (anti-TNFi Abs). Methods Blood samples from 26 patients with established RA were taken at baseline and following 6 months of treatment with adalimumab or infliximab. Samples were analyzed for levels of TNFi, interleukin (IL)-6, and soluble TNF-receptors 1 and -2 (sTNF-R1 and -2) and for presence of anti-TNFi Abs. Clinical and demographic data were recorded as well. Results During the initial 6 months treatment, DAS28(CRP) (Disease activity score in 28 joints using C-reactive protein) and levels of IL-6 and sTNF-R2 decreased significantly in patients without anti-TNFi Abs and in patients retaining detectable drug levels. The levels of other tested cytokines (TNF-α, TNF-β, IL-1ra, IL-1b, IL-8, IL-10, IL-12(p70), IL-13, IL-17A, IL-17F, and IL-33) were generally below detection limits. Higher baseline levels of IL-6 associated with undetectable levels of TNFi at follow-up. Anti-TNFi Abs were associated with decreased drug levels, but no predictors for anti-TNFi Ab development could be found. Conclusion The effect of treatment with TNFi on RA disease activity depends on levels of active drug, and by presence of anti-TNFi Abs. In patients who retain detectable drug levels, and in the absence of anti-TNFi Abs, clinical outcome is improved during treatment, and circulating levels of IL-6 and sTNF-R2 decrease. Baseline levels of IL-6 may predict depletion of TNFi and may identify patients at risk of treatment failure. |
Databáze: | OpenAIRE |
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