Why the findings of published multiple treatment comparison meta-analyses of biologic treatments for rheumatoid arthritis are different: an overview of recurrent methodological shortcomings

Thorlund, Kristian; Druyts, Eric; Aviña‐Zubieta, J Antonio; Wu, Ping; Mills, Edward J.

doi:10.1136/annrheumdis-2012-201574

Cited by 39 publications

(37 citation statements)

References 27 publications

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“…Thorlund and colleagues have used informative priors to estimate variance and improve precision of the analysis. 41 Our group recently published a comparative effectiveness study for anti-TNF agents in ulcerative colitis showing a trend of IFX superiority over ADA for induction (RR = 0.46, 95% CrI: 0.10-3.05). 42 Thorlund and colleagues also performed NMA yielding a comparable point estimate of IFX superiority over ADA, but using informative priors they reported statistical significance (OR = 0.42, 95% CrI: 0.17-0.97).…”

Section: Discussionmentioning

confidence: 99%

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

Stidham

Lee

Higgins

et al. 2014

Aliment Pharmacol Ther

183

107

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SummaryBackgroundAnti‐tumour necrosis factor‐alpha agents (anti‐TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown.AimTo perform a network meta‐analysis comparing the efficacy of anti‐TNF therapies in CD.MethodsAfter screening 506 studies, reviewers extracted information on 10 studies. Traditional meta‐analysis (TMA) was used to compare each anti‐TNF agent to placebo. Bayesian network meta‐analysis (NMA) was performed to compare the effects of anti‐TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated.ResultsCompared to placebo, TMA revealed that anti‐TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17–2.36 and RR: 1.43, 95% CI: 1.17–1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51–2.09 and RR: 1.68, 95% CI: 1.46–1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21–7.75). Sample size calculations suggest that adequately powered head‐to‐head comparative efficacy trials would require greater than 3000 patients.ConclusionsAll anti‐TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti‐TNF agents. Head‐to‐head trials among the anti‐TNF agents are impractical in terms of size and cost.

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Section: Discussionmentioning

confidence: 99%

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

Stidham

Lee

Higgins

et al. 2014

Aliment Pharmacol Ther

183

107

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“…The BEST (Behandelstrategie€ en voor Reumatoide Artritis; Treatment Strategies for Rheumatoid Arthritis) study (3,4) was the first to indicate that a combination of conventional DMARDs might have the same effect as a TNF inhibitor plus methotrexate. As recently reviewed, 13 very similar network meta-analyses have shown similarity of different biologic agents (22), but the relative effects of a combination of conventional DMARDs versus biologic agents have only been compared indirectly in 1 network meta-analysis (2) and in 2 conventional meta-analyses (1,23). Consequently, the present analysis is the first to integrate all available evidence directly comparing a combination of DMARDs versus a biologic treatment plus methotrexate, and is also the first to estimate the effect at consecutive time points during a period of 2 years.…”

Section: Discussionmentioning

confidence: 97%

“…Consequently, the present analysis is the first to integrate all available evidence directly comparing a combination of DMARDs versus a biologic treatment plus methotrexate, and is also the first to estimate the effect at consecutive time points during a period of 2 years. Although only TNF inhibitors were investigated, it is likely that the present results could be extended to other biologic agents, as the biologic agents in general have been shown to be equally efficacious (2,22,24).…”

Section: Discussionmentioning

confidence: 97%

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

Graudal

Hubeck-Graudal

Faurschou

et al. 2015

Arthritis Care & Research

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Objective. The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. Methods. Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method (dichotomous data) using a random-effects model. Results. The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (20.09 units [20.61, 0.44]) of treatment or during the first 2 years (0.66 units [20.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids. Conclusion. The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors.

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“…When incoherence exists, which results one should use as the best estimate (direct, indirect, or network) remains controversial [6,26]. If one body of evidence warrants higher certainty than the other (this will usually but not always be the direct evidence), one can argue strongly that the body of evidence in which there is more certainty represents the best estimate of the true effect [23].…”

Section: Do Indirect Comparisons Respect the Transitivity Principle?mentioning

confidence: 99%

Network Meta-analysis: Users’ Guide for Surgeons: Part II - Certainty

Chaudhry

Foote

Guyatt

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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In the previous article (Network Meta-analysis: Users' Guide for Surgeons-Part I, Credibility), we presented an approach to evaluating the credibility or methodologic rigor of network meta-analyses (NMA), an innovative approach to simultaneously addressing the relative effectiveness of three or more treatment options for a given medical condition or disease state. In the second part of the Users' Guide for Surgeons, we discuss and demonstrate the application of criteria for determining the certainty in effect sizes and directions associated with a given treatment option through an example pertinent to clinical orthopaedics.

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Why the findings of published multiple treatment comparison meta-analyses of biologic treatments for rheumatoid arthritis are different: an overview of recurrent methodological shortcomings

Abstract: The identified methodological shortcomings and inconsistencies most likely explain the observed discrepancies in findings across MTCs.

Cited by 39 publications

References 27 publications

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

Network Meta-analysis: Users’ Guide for Surgeons: Part II - Certainty

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