Dataset Information

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

ABSTRACT:

Background

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).

Methods and findings

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 ? 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)).

Conclusion

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.

SUBMITTER: Graudal N

PROVIDER: S-EPMC4171366 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Graudal Niels N Hubeck-Graudal Thorbjørn T Tarp Simon S Christensen Robin R Jürgens Gesche G

PloS one 20140922 9

<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 investigat ...[more]

PMID: 25244021

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Project description:ObjectiveRheumatoid arthritis (RA) is a chronic disease leading to joint destruction. Although many studies have addressed factors potentially correlated with the speed of joint destruction, less attention has been paid to the distribution of joint destruction in patients with RA. In this study, destruction of the hand bones in patients with RA was classified into 2 anatomic subgroups, the fingers and the non-fingers, with the aim of analyzing which factors are associated with destruction of the finger joints.MethodsA total of 1,215 Japanese patients with RA were recruited from 2 different populations. The degree of joint destruction was assessed using the total modified Sharp/van der Heijde score (SHS) of radiographic joint damage. The SHS score of joint damage in the finger joints was used as the dependent variable, and the SHS score in the non-finger joints was used as a covariate. Age, sex, disease duration, smoking, C-reactive protein level, treatment for RA, and positivity for and levels of anti-citrullinated protein antibodies and rheumatoid factor (RF) were evaluated as candidate correlates. Overall effect sizes were assessed in a meta-analysis. In addition, associations observed in the Japanese patients were compared to those in a cohort of 157 Dutch RA patients in the BeSt study (a randomized, controlled trial involving 4 different strictly specified treatment strategies for early RA).ResultsNot surprisingly, disease duration in Japanese patients with RA was associated with the finger SHS score (P ≤ 0.00037). Both positivity for and levels of RF showed significant associations with the finger SHS score after adjustment for covariates (P = 0.0022 and P = 8.1 × 10(-7) , respectively). These associations were also true in relation to the time-averaged finger SHS score. An association between RF positivity and the finger SHS score was also observed in Dutch patients with RA in the BeSt study (P = 0.049).ConclusionPositivity for and levels of RF are associated with finger joint destruction independent of non-finger joint destruction and other covariates. Our findings suggest that there are different mechanisms of joint destruction operating in the finger joints of patients with RA.

Project description:INTRODUCTION: Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor ? B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA. METHODS: 1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied. RESULTS: We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P?=?2.35x10-4). This variant was also significant after Bonferroni correction. CONCLUSIONS: These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA.

Dataset Information

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

Background

Methods and findings

Conclusion

Publications

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

Similar Datasets

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