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Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis

INTRODUCTION: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possibl...

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Autores principales: Ooms, Alexander, Al-Mossawi, Hussein, Bennett, Louise, Bogale, Mimi, Bowness, Paul, Francis, Anne, Goodyear, Carl, Kirkham, Bruce W, Lalnunhlimi, Sylvine, McInnes, Iain B, Richards, Duncan, Siebert, Stefan, Taams, Leonie S, Tulunay Virlan, Aysin, Yager, Nicole, Coates, Laura C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546161/
https://www.ncbi.nlm.nih.gov/pubmed/37770264
http://dx.doi.org/10.1136/bmjopen-2023-078539
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author Ooms, Alexander
Al-Mossawi, Hussein
Bennett, Louise
Bogale, Mimi
Bowness, Paul
Francis, Anne
Goodyear, Carl
Kirkham, Bruce W
Lalnunhlimi, Sylvine
McInnes, Iain B
Richards, Duncan
Siebert, Stefan
Taams, Leonie S
Tulunay Virlan, Aysin
Yager, Nicole
Coates, Laura C
author_facet Ooms, Alexander
Al-Mossawi, Hussein
Bennett, Louise
Bogale, Mimi
Bowness, Paul
Francis, Anne
Goodyear, Carl
Kirkham, Bruce W
Lalnunhlimi, Sylvine
McInnes, Iain B
Richards, Duncan
Siebert, Stefan
Taams, Leonie S
Tulunay Virlan, Aysin
Yager, Nicole
Coates, Laura C
author_sort Ooms, Alexander
collection PubMed
description INTRODUCTION: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response. This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. METHODS AND ANALYSIS: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. TRIAL REGISTRATION NUMBER: ISRCTN17228602.
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spelling pubmed-105461612023-10-04 Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis Ooms, Alexander Al-Mossawi, Hussein Bennett, Louise Bogale, Mimi Bowness, Paul Francis, Anne Goodyear, Carl Kirkham, Bruce W Lalnunhlimi, Sylvine McInnes, Iain B Richards, Duncan Siebert, Stefan Taams, Leonie S Tulunay Virlan, Aysin Yager, Nicole Coates, Laura C BMJ Open Rheumatology INTRODUCTION: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response. This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. METHODS AND ANALYSIS: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. TRIAL REGISTRATION NUMBER: ISRCTN17228602. BMJ Publishing Group 2023-09-28 /pmc/articles/PMC10546161/ /pubmed/37770264 http://dx.doi.org/10.1136/bmjopen-2023-078539 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Rheumatology
Ooms, Alexander
Al-Mossawi, Hussein
Bennett, Louise
Bogale, Mimi
Bowness, Paul
Francis, Anne
Goodyear, Carl
Kirkham, Bruce W
Lalnunhlimi, Sylvine
McInnes, Iain B
Richards, Duncan
Siebert, Stefan
Taams, Leonie S
Tulunay Virlan, Aysin
Yager, Nicole
Coates, Laura C
Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
title Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
title_full Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
title_fullStr Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
title_full_unstemmed Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
title_short Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
title_sort optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis
topic Rheumatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546161/
https://www.ncbi.nlm.nih.gov/pubmed/37770264
http://dx.doi.org/10.1136/bmjopen-2023-078539
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