Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Eng, Grith Petersen, Bouchelouche, Pierre, Bartels, Else Marie, Bliddal, Henning, Bendtzen, Klaus, Stoltenberg, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016088/
https://www.ncbi.nlm.nih.gov/pubmed/27606615
http://dx.doi.org/10.1371/journal.pone.0162316
_version_ 1782452538601111552
author Eng, Grith Petersen
Bouchelouche, Pierre
Bartels, Else Marie
Bliddal, Henning
Bendtzen, Klaus
Stoltenberg, Michael
author_facet Eng, Grith Petersen
Bouchelouche, Pierre
Bartels, Else Marie
Bliddal, Henning
Bendtzen, Klaus
Stoltenberg, Michael
author_sort Eng, Grith Petersen
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5016088
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-50160882016-09-27 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 Eng, Grith Petersen Bouchelouche, Pierre Bartels, Else Marie Bliddal, Henning Bendtzen, Klaus Stoltenberg, Michael PLoS One Research Article 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. Public Library of Science 2016-09-08 /pmc/articles/PMC5016088/ /pubmed/27606615 http://dx.doi.org/10.1371/journal.pone.0162316 Text en © 2016 Eng et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Eng, Grith Petersen
Bouchelouche, Pierre
Bartels, Else Marie
Bliddal, Henning
Bendtzen, Klaus
Stoltenberg, Michael
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016088/
https://www.ncbi.nlm.nih.gov/pubmed/27606615
http://dx.doi.org/10.1371/journal.pone.0162316
work_keys_str_mv AT enggrithpetersen antidrugantibodiesdruglevelsinterleukin6andsolubletnfreceptorsinrheumatoidarthritispatientsduringthefirst6monthsoftreatmentwithadalimumaborinfliximabadescriptivecohortstudy
AT bouchelouchepierre antidrugantibodiesdruglevelsinterleukin6andsolubletnfreceptorsinrheumatoidarthritispatientsduringthefirst6monthsoftreatmentwithadalimumaborinfliximabadescriptivecohortstudy
AT bartelselsemarie antidrugantibodiesdruglevelsinterleukin6andsolubletnfreceptorsinrheumatoidarthritispatientsduringthefirst6monthsoftreatmentwithadalimumaborinfliximabadescriptivecohortstudy
AT bliddalhenning antidrugantibodiesdruglevelsinterleukin6andsolubletnfreceptorsinrheumatoidarthritispatientsduringthefirst6monthsoftreatmentwithadalimumaborinfliximabadescriptivecohortstudy
AT bendtzenklaus antidrugantibodiesdruglevelsinterleukin6andsolubletnfreceptorsinrheumatoidarthritispatientsduringthefirst6monthsoftreatmentwithadalimumaborinfliximabadescriptivecohortstudy
AT stoltenbergmichael antidrugantibodiesdruglevelsinterleukin6andsolubletnfreceptorsinrheumatoidarthritispatientsduringthefirst6monthsoftreatmentwithadalimumaborinfliximabadescriptivecohortstudy