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BioMed Research International
Volume 2014 (2014), Article ID 831603, 17 pages
Review Article

Treatment Comparison in Rheumatoid Arthritis: Head-to-Head Trials and Innovative Study Designs

1Department of Rheumatology, Gaetano Pini Institute Via Gaetano Pini 9, 20121 Milano, Italy
2Division of Rheumatology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Piazzale Golgi 2, 27100 Pavia, Italy

Received 22 January 2014; Accepted 15 March 2014; Published 16 April 2014

Academic Editor: Lorenzo Cavagna

Copyright © 2014 Ennio Giulio Favalli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Over the last decades, the increasing knowledge in the area of rheumatoid arthritis has progressively expanded the arsenal of available drugs, especially with the introduction of novel targeted therapies such as biological disease modifying antirheumatic drugs (DMARDs). In this situation, rheumatologists are offered a wide range of treatment options, but on the other side the need for comparisons between available drugs becomes more and more crucial in order to better define the strategies for the choice and the optimal sequencing. Indirect comparisons or meta-analyses of data coming from different randomised controlled trials (RCTs) are not immune to conceptual and technical challenges and often provide inconsistent results. In this review we examine some of the possible evolutions of traditional RCTs, such as the inclusion of active comparators, aimed at individualising treatments in real-life conditions. Although head-to-head RCTs may be considered the best tool to directly compare the efficacy and safety of two different DMARDs, surprisingly only 20 studies with such design have been published in the last 25 years. Given the recent advent of the first RCTs truly comparing biological DMARDs, we also review the state of the art of head-to-head trials in RA.