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
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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