Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.

<h4>Background</h4>Despite significant cost differences, the comparative effect of combination treatments of disease modifying anti-rheumatic drugs (DMARDs) with and without biologic agents has rarely been examined. Thus we performed a network meta-analysis on the effect of combination t...

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Autores principales:	Niels Graudal, Thorbjørn Hubeck-Graudal, Simon Tarp, Robin Christensen, Gesche Jürgens
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d897734687740f9ba61a5f5532b4887
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spelling	oai:doaj.org-article:4d897734687740f9ba61a5f5532b48872021-11-25T05:59:51ZEffect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.1932-620310.1371/journal.pone.0106408https://doaj.org/article/4d897734687740f9ba61a5f5532b48872014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0106408https://doaj.org/toc/1932-6203<h4>Background</h4>Despite significant cost differences, the comparative effect of combination treatments of disease modifying anti-rheumatic drugs (DMARDs) with and without biologic agents has rarely been examined. Thus we performed a network meta-analysis on the effect of combination therapies on progression of radiographic joint erosions in patients with rheumatoid arthritis (RA).<h4>Methods and findings</h4>The following combination drug therapies compared versus single DMARD were investigated: Double DMARD: 2 DMARDs (methotrexate, sulfasalazine, leflunomide, injectable gold, cyclosporine, chloroquine, azathioprin, penicillamin) or 1 DMARD plus low dose glucocorticoid (LDGC); triple DMARD: 3 DMARDs or 2 DMARDs plus LDGC; biologic combination: 1 DMARD plus biologic agent (tumor necrosis factor α inhibitor (TNFi) or abatacept or tocilizumab or CD20 inhibitor (CD20i)). Randomized controlled trials were identified in a search of electronic archives of biomedical literature and included in a star-shaped network meta-analysis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. Effects are reported as standardized mean differences (SMD). The effects of data from 39 trials published in the period 1989-2012 were as follows: Double DMARD: -0.32 SMD (CI: -0.42, -0.22); triple DMARD: -0.46 SMD (CI: -0.60, -0.31); 1 DMARD plus TNFi: -0.30 SMD (CI: -0.36, -0.25); 1 DMARD plus abatacept: -0.20 SMD (CI: -0.33, -0.07); 1 DMARD plus tocilizumab: -0.34 SMD (CI: -0.48, -0.20); 1 DMARD plus CD20i: -0.32 SMD (CI: -0.40, -0.24). The indirect comparisons showed similar effects between combination treatments apart from triple DMARD being significantly better than abatacept plus methotrexate (-0.26 SMD (CI: -0.45, -0.07)) and TNFi plus methotrexate (-0.16 SMD (CI: -0.31, -0.01)).<h4>Conclusion</h4>Combination treatment of a biologic agent with 1 DMARD is not superior to 2-3 DMARDs including or excluding LDGC in preventing structural joint damage. Future randomized studies of biologic agents should be compared versus a combination of DMARDs.Niels GraudalThorbjørn Hubeck-GraudalSimon TarpRobin ChristensenGesche JürgensPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e106408 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Niels Graudal Thorbjørn Hubeck-Graudal Simon Tarp Robin Christensen Gesche Jürgens Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
description	<h4>Background</h4>Despite significant cost differences, the comparative effect of combination treatments of disease modifying anti-rheumatic drugs (DMARDs) with and without biologic agents has rarely been examined. Thus we performed a network meta-analysis on the effect of combination therapies on progression of radiographic joint erosions in patients with rheumatoid arthritis (RA).<h4>Methods and findings</h4>The following combination drug therapies compared versus single DMARD were investigated: Double DMARD: 2 DMARDs (methotrexate, sulfasalazine, leflunomide, injectable gold, cyclosporine, chloroquine, azathioprin, penicillamin) or 1 DMARD plus low dose glucocorticoid (LDGC); triple DMARD: 3 DMARDs or 2 DMARDs plus LDGC; biologic combination: 1 DMARD plus biologic agent (tumor necrosis factor α inhibitor (TNFi) or abatacept or tocilizumab or CD20 inhibitor (CD20i)). Randomized controlled trials were identified in a search of electronic archives of biomedical literature and included in a star-shaped network meta-analysis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. Effects are reported as standardized mean differences (SMD). The effects of data from 39 trials published in the period 1989-2012 were as follows: Double DMARD: -0.32 SMD (CI: -0.42, -0.22); triple DMARD: -0.46 SMD (CI: -0.60, -0.31); 1 DMARD plus TNFi: -0.30 SMD (CI: -0.36, -0.25); 1 DMARD plus abatacept: -0.20 SMD (CI: -0.33, -0.07); 1 DMARD plus tocilizumab: -0.34 SMD (CI: -0.48, -0.20); 1 DMARD plus CD20i: -0.32 SMD (CI: -0.40, -0.24). The indirect comparisons showed similar effects between combination treatments apart from triple DMARD being significantly better than abatacept plus methotrexate (-0.26 SMD (CI: -0.45, -0.07)) and TNFi plus methotrexate (-0.16 SMD (CI: -0.31, -0.01)).<h4>Conclusion</h4>Combination treatment of a biologic agent with 1 DMARD is not superior to 2-3 DMARDs including or excluding LDGC in preventing structural joint damage. Future randomized studies of biologic agents should be compared versus a combination of DMARDs.
format	article
author	Niels Graudal Thorbjørn Hubeck-Graudal Simon Tarp Robin Christensen Gesche Jürgens
author_facet	Niels Graudal Thorbjørn Hubeck-Graudal Simon Tarp Robin Christensen Gesche Jürgens
author_sort	Niels Graudal
title	Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
title_short	Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
title_full	Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
title_fullStr	Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
title_full_unstemmed	Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
title_sort	effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4d897734687740f9ba61a5f5532b4887
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Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials.

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