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Systematic Review and Meta-Analysis of the Efficacy and Safety of Existing TNF Blocking Agents in Treatment of Rheumatoid Arthritis

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  • Kalle J Aaltonen
  • Liisa M Virkki
  • Antti Malmivaara
  • Yrjö T Konttinen
  • Dan C Nordström
  • Marja Blom

Abstract

Background and Objectives: Five-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT). Methods: A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias. Results: Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo. Conclusions: No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

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  • Kalle J Aaltonen & Liisa M Virkki & Antti Malmivaara & Yrjö T Konttinen & Dan C Nordström & Marja Blom, 2012. "Systematic Review and Meta-Analysis of the Efficacy and Safety of Existing TNF Blocking Agents in Treatment of Rheumatoid Arthritis," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-14, January.
    • Handle: RePEc:plo:pone00:0030275
    DOI: 10.1371/journal.pone.0030275
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    Cited by:

    1. Petra Baji & Márta Péntek & László Czirják & Zoltán Szekanecz & György Nagy & László Gulácsi & Valentin Brodszky, 2014. "Efficacy and safety of infliximab-biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison," The European Journal of Health Economics, Springer;Deutsche Gesellschaft für Gesundheitsökonomie (DGGÖ), vol. 15(1), pages 53-64, May.
    2. Jaana T Joensuu & Saara Huoponen & Kalle J Aaltonen & Yrjö T Konttinen & Dan Nordström & Marja Blom, 2015. "The Cost-Effectiveness of Biologics for the Treatment of Rheumatoid Arthritis: A Systematic Review," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-27, March.
    3. Saara Huoponen & Kalle J Aaltonen & Jaana Viikinkoski & Jarno Rutanen & Heikki Relas & Kirsi Taimen & Kari Puolakka & Dan Nordström & Marja Blom, 2019. "Cost-effectiveness of abatacept, tocilizumab and TNF-inhibitors compared with rituximab as second-line biologic drug in rheumatoid arthritis," PLOS ONE, Public Library of Science, vol. 14(7), pages 1-14, July.

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