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Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors

Regina Rendas-Baum1, Gene V Wallenstein2*, Tamas Koncz3, Mark Kosinski1, Min Yang1, John Bradley2 and Samuel H Zwillich2

Author Affiliations

1 QualityMetric Inc., Outcomes Insight Consulting Division, 24 Albion Road, Lincoln, RI 02865, USA

2 Pfizer Clinical Development and Medical Affairs, 50 Pequot Avenue, 6025-B3206, New London, CT 06320, USA

3 Pfizer Clinical Development and Medical Affairs, 235 East 42nd Street, New York, NY 10017, USA

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Arthritis Research & Therapy 2011, 13:R25  doi:10.1186/ar3249

Published: 16 February 2011



The long-term treatment of rheumatoid arthritis (RA) most often involves a sequence of different therapies. The response to therapy, disease progression and detailed knowledge of the role of different therapies along treatment pathways are key aspects to help physicians identify the best treatment strategy. Thus, understanding the effectiveness of different therapeutic sequences is of particular importance in the evaluation of long-term RA treatment strategies. The objective of this study was to systematically review and quantitatively evaluate the relationship between the clinical response to biologic treatments and the number of previous treatments with tumor necrosis factor α (TNF-α) inhibitors.


A systematic search was undertaken to identify published, peer-reviewed articles that reported clinical outcomes of biologic treatment among RA patients with an inadequate response to TNF-α inhibitors. Data were systematically abstracted. Efficacy rates were estimated for groups of patients who differed in the number of prior TNF-α inhibitors used. End points included American College of Rheumatology (ACR)-, European League Against Rheumatism (EULAR)- and Disease Activity Score 28 (DAS28)-based response criteria.


The literature search identified 41 publications, of which 28 reported biologic treatment outcomes for RA patients with prior exposure to TNF-α inhibitors. Seven publications reported outcomes obtained in randomized clinical trials, while the remaining consisted of observational studies. The likelihood of responding to a subsequent biologic treatment decreased as the number of previous treatments with TNF-α inhibitors increased for six of the seven response criteria examined.


For patients with prior exposure to TNF-α inhibitors, the likelihood of response to subsequent treatment with biologic agents declines with the increasing number of previous treatments with TNF-α inhibitors.