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Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylos...

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Autores principales: Sepriano, Alexandre, Ramiro, Sofia, van der Heijde, Desirée, Landewé, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276290/
https://www.ncbi.nlm.nih.gov/pubmed/34253683
http://dx.doi.org/10.1136/rmdopen-2021-001654
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author Sepriano, Alexandre
Ramiro, Sofia
van der Heijde, Desirée
Landewé, Robert
author_facet Sepriano, Alexandre
Ramiro, Sofia
van der Heijde, Desirée
Landewé, Robert
author_sort Sepriano, Alexandre
collection PubMed
description Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA.
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spelling pubmed-82762902021-07-27 Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference Sepriano, Alexandre Ramiro, Sofia van der Heijde, Desirée Landewé, Robert RMD Open Spondyloarthritis Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA. BMJ Publishing Group 2021-07-12 /pmc/articles/PMC8276290/ /pubmed/34253683 http://dx.doi.org/10.1136/rmdopen-2021-001654 Text en © Author(s) (or their employer(s)) 2021. 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 Spondyloarthritis
Sepriano, Alexandre
Ramiro, Sofia
van der Heijde, Desirée
Landewé, Robert
Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference
title Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference
title_full Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference
title_fullStr Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference
title_full_unstemmed Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference
title_short Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference
title_sort biological dmards and disease modification in axial spondyloarthritis: a review through the lens of causal inference
topic Spondyloarthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276290/
https://www.ncbi.nlm.nih.gov/pubmed/34253683
http://dx.doi.org/10.1136/rmdopen-2021-001654
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