Extended report the reported radiographic progression favoured the intensive treatment (table 1). Additional studies A number of studies used the treat to target concept, but, in contrast to the mentioned papers, did not have a non-targeted control arm, since all arms pursued the same target with dif- ferent treatment sequences (supplementary table S4). Likewise, several trials compared step-up with combination regimes, dose titration of agents or different therapies to reach a deﬁned target without directly addressing the efﬁcacy of treating to target. A description of these studies can be found in the supplementary material accompanying this manuscript. DISCUSSION Our review revealed that only few controlled studies investi- gated the value of strategic treatment schedules. Importantly, study designs and evaluated targets were very heterogeneous; for example, the Edmonds and van Tuyl studies are inher- ently different in design as compared to the others in that their approach compares two T2T approaches while the others com- pare a T2T approach with the routine approach. Nevertheless, all studies investigating early disease showed signiﬁcantly better clinical outcomes of the targeted approach. Functional outcomes, reported in two trials, failed to show signiﬁcant gains.27 29 Four studies compared radiographic outcomes,26 27 29 32 of which two showed a signiﬁcant beneﬁt of the targeted therapy.26 Five26–28 30 32 studies investigated early disease (using different deﬁnitions of ‘early’ – see supplementary table S3). Only one trial29 focused explicitly on late disease (duration: >5 years) and found no advantage of tight control on functional outcomes. Thus, patients with established RA seem to be underinvesti- gated regarding the value of treating to a target. Since longer dis- ease duration impairs treatment outcomes,33 extending results from early RA to the general patient population could be mis- leading. Furthermore, just focusing on HAQ might also be mis- guiding, since with increasing disease duration responsiveness of physical function to therapeutic interventions decreases (even to placebo levels).34 Utilised targets showed considerable heterogeneity (table 1, ﬁgure 2). Among the randomised trials comparing targeted versus routine approaches, three out of four employed state targets,26 28 29 an approach that has been favoured as being more appropriate than assessing changes from baseline.35 Only in CAMERA,27 the target was formulated as reaching deﬁned improvement criteria. Also, visit intervals were notice- ably heterogenous: clinical assessments were performed from monthly26–28 31 to every 429 36 months. Two trials randomised patients to different visit intervals.26 37 In both, patients assigned to intensive strategy were seen monthly, those in routine care every 3 months. In conclusion, only few studies have used a randomised approach to test the value of treatment to a speciﬁc target. However, all of them provided compelling evidence of clin- ical beneﬁts of such an approach. However, more data are needed concerning radiographic and functional outcomes and patients with longstanding RA have not been sufﬁciently investigated. Author afﬁliations 12nd Department of Internal Medicine, Centre for Rheumatic Diseases, Hietzing Hospital, Vienna, Austria 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands 642 03_ar123976.indd 642 3Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria 4Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands 5Department of Internal Medicine, University of Crete Medical School, Heraklion, Greece 6Department of Rheumatology and Clinical Immunology, Humboldt University, Charité Hospital, Berlin, Germany 7Service d’Immuno-Rhumatologie, Montpellier University, Lapeyronie Hospital, Montpellier, France 8Research Laboratory and Academic Clinical Unit of Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy 9Department of Rheumatology B, René Descartes University, Cochin Hospital, Paris, France 10Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK 11Department of Internal Medicine III, Institute for Clinical Immunology at the Friedrich- Alexander University, Erlangen, Germany 12 Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, Toronto, Canada 13Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway 14La Paz Hospital, Madrid, Spain 15Department of Rheumatology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy 16EULAR Standing Committee of People with Arthritis/Rheumatism in Europe, Zurich, Switzerland MS and RK Contributed equally to this study. Competing interests This study was supported by an unrestricted educational grant from Abbott Immunology. Abbott had no inﬂuence on the selection of papers, extraction of data or writing of this manuscript. Francis Berenbaum was the Handling Editor. Provenance and peer review Not commissioned; externally peer reviewed. REFERENCES 1. Smolen JS, Aletaha D, Koeller M, et al. New therapies for treatment of rheumatoid arthritis. Lancet 2007;370:1861–74. 2. Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 2008;372:375–82. 3. Combe B, Landewe R, Lukas C, et al. 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