Cargando…

A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study

BACKGROUND: Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we...

Descripción completa

Detalles Bibliográficos
Autores principales: Stradner, Martin H., Dejaco, Christian, Brickmann, Kerstin, Graninger, Winfried B., Brezinschek, Hans Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997751/
https://www.ncbi.nlm.nih.gov/pubmed/27558631
http://dx.doi.org/10.1186/s13075-016-1091-1
_version_ 1782449836287590400
author Stradner, Martin H.
Dejaco, Christian
Brickmann, Kerstin
Graninger, Winfried B.
Brezinschek, Hans Peter
author_facet Stradner, Martin H.
Dejaco, Christian
Brickmann, Kerstin
Graninger, Winfried B.
Brezinschek, Hans Peter
author_sort Stradner, Martin H.
collection PubMed
description BACKGROUND: Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we investigated whether lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment. METHODS: Patients with RA who were receiving RTX for the first time were included in an observatory registry. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline and at week 24 after RTX. Complete data were available for 44 patients. Logistic regression and receiver operating characteristic curve analyses were computed to analyze the predictive value of lymphocyte subsets for European League Against Rheumatism (EULAR) response and LDA (defined as disease activity score in 28 joints (DAS28) ≤3.2) at week 24. RESULTS: EULAR responders had lower total lymphocyte counts (LC), T cells and CD4 + T cells at baseline. Although these parameters were independent predictors of EULAR response they failed in determining who would reach LDA. In contrast, LC >2910/μl or plasmablast frequency >2.85 % at baseline predicted a significantly higher DAS28 at week 24 after RTX and identified patients not achieving LDA at week 24 with sensitivity of 93.3 % and specificity of 44.8 %. CONCLUSIONS: A combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-016-1091-1) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4997751
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-49977512016-08-26 A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study Stradner, Martin H. Dejaco, Christian Brickmann, Kerstin Graninger, Winfried B. Brezinschek, Hans Peter Arthritis Res Ther Research Article BACKGROUND: Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we investigated whether lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment. METHODS: Patients with RA who were receiving RTX for the first time were included in an observatory registry. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline and at week 24 after RTX. Complete data were available for 44 patients. Logistic regression and receiver operating characteristic curve analyses were computed to analyze the predictive value of lymphocyte subsets for European League Against Rheumatism (EULAR) response and LDA (defined as disease activity score in 28 joints (DAS28) ≤3.2) at week 24. RESULTS: EULAR responders had lower total lymphocyte counts (LC), T cells and CD4 + T cells at baseline. Although these parameters were independent predictors of EULAR response they failed in determining who would reach LDA. In contrast, LC >2910/μl or plasmablast frequency >2.85 % at baseline predicted a significantly higher DAS28 at week 24 after RTX and identified patients not achieving LDA at week 24 with sensitivity of 93.3 % and specificity of 44.8 %. CONCLUSIONS: A combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-016-1091-1) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-24 2016 /pmc/articles/PMC4997751/ /pubmed/27558631 http://dx.doi.org/10.1186/s13075-016-1091-1 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Stradner, Martin H.
Dejaco, Christian
Brickmann, Kerstin
Graninger, Winfried B.
Brezinschek, Hans Peter
A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
title A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
title_full A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
title_fullStr A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
title_full_unstemmed A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
title_short A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
title_sort combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997751/
https://www.ncbi.nlm.nih.gov/pubmed/27558631
http://dx.doi.org/10.1186/s13075-016-1091-1
work_keys_str_mv AT stradnermartinh acombinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT dejacochristian acombinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT brickmannkerstin acombinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT graningerwinfriedb acombinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT brezinschekhanspeter acombinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT stradnermartinh combinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT dejacochristian combinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT brickmannkerstin combinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT graningerwinfriedb combinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy
AT brezinschekhanspeter combinationofcellularbiomarkerspredictsfailuretorespondtorituximabinrheumatoidarthritisa24weekobservationalstudy