Extended report ▶ Additional data are published online only at http://ard.bmj. com/content/vol69/issue4 For numbered afﬁliations see end of the article Correspondence to Daniel Aletaha, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria; daniel.aletaha@meduniwien. ac.at Accepted 28 January 2010 This paper is freely available online under the BMJ Journals unlocked scheme, see http:// ard.bmj.com/info/unlocked.dtl 638 Evidence for treating rheumatoid arthritis to target: results of a systematic literature search Monika Schoels,1 Rachel Knevel,2 Daniel Aletaha,3 Johannes W J Bijlsma,4 Ferdinand C Breedveld,2 Dimitrios T Boumpas,5 Gerd Burmester,6 Bernard Combe,7 Maurizio Cutolo,8 Maxime Dougados,9 Paul Emery,10 Desirée van der Heijde,2 Tom W J Huizinga,2 Joachim Kalden,11 Edward C Keystone,12 Tore K Kvien,13 Emilio Martin-Mola,14 Carlomaurizio Montecucco,15 Maarten de Wit,16 Josef S Smolen1,3 ABSTRACT Objectives To summarise existing evidence on a target oriented approach for rheumatoid arthritis (RA) treatment. Methods We conducted a systematic literature search including all clinical trials testing clinical, functional, or structural values of a targeted treatment approach. Our search covered Medline, Embase and Cochrane databases until December 2008 and also conference abstracts (2007, 2008). Results The primary search yielded 5881 citations; after the selection process, 76 papers underwent detailed review. Of these, only seven strategic clinical trials were extracted: four studies randomised patients to routine or targeted treatment, two compared two different randomised targets and one compared targeted treatment to a historical control group. Five trials dealt with early RA patients. All identiﬁed studies showed signiﬁcantly better clinical outcomes of targeted approaches than routine approaches. Disability was reported in two studies with no difference between groups. Four studies compared radiographic outcomes, two showing signiﬁcant beneﬁt of the targeted approach. Conclusion Only few studies employed randomised controlled settings to test the value of treatment to a speciﬁc target. However, they provided unanimous evidence for beneﬁts of targeted approaches. Nevertheless, more data on radiographic and functional outcomes and on patients with established RA are needed. INTRODUCTION Many new treatment options make unprecedented outcomes achievable in rheumatoid arthritis (RA).1 2 In parallel, insights on the importance of early effective therapy3 4 and implications of dis- ease activity on function5 6 and joint damage6–8 led to paradigmatic changes in therapeutic approaches, such as frequent evaluations of disease activ- ity to allow for timely changes of therapies.9–13 Additionally, validated composite disease activity measures have made disease activity assessment easy.14 15 Nevertheless, heterogeneity of therapeu- tic aims and patient expectations16 characterise daily practice of RA treatment.17 All this suggests a need to provide rheumatologists and patients with pertinent information on therapeutic targets and means to achieve them.18 19 Strict deﬁnitions of treatment targets intend to facilitate strategic acting in routine care and require physicians and patients to discuss and adopt therapeutic changes within distinct time frames, ideally following therapeutic algorithms. This approach has been utilised in many diseases, like diabetes,20 21 hypertension22–24 or hyper- lipidaemia.25 However, this policy needs to be evi- dence based to the best possible extent. Here we report on a systematic review of avail- able evidence regarding the effects of treating RA strategically according to deﬁned outcome targets. METHODS Shaping the systematic literature review As a ﬁrst step, the international steering commit- tee of the Treat-To-Target (T2T) project, compris- ing a group of expert rheumatologists and a patient (MdW), designed a literature search that aimed at ‘treating to target’-strategy trials in RA. The search was then performed by a project fellow (MS), a control search by a second fellow (RK) and by two mentors (DA, DvdH). The following deﬁnitions were made: (1) strat- egy trial – clinical trial of any RA drug treatment, in which a clear outcome target was the primary end point and therapeutic consequences of failing to reach the target were predeﬁned; (2) targets – a target could be formulated by clinical, serological, patient-reported, functional, or radiographic vari- ables; individual measures (eg, joint counts or acute phase reactants), composite scores (eg, disease activ- ity score or simpliﬁed disease activity index), or response criteria (eg, those deﬁned by the American College of Rheumatology (ACR) or the European League Against Rheumatism) were considered alike; (3) outcomes – Clinical, functional, serological and/or radiographic changes, as deﬁned in the respective trials, were compared between treatment groups. Implementation of the systematic literature review We searched Medline, Embase and Cochrane data- bases from their inception until December 2008. Additionally, ACR and European League Against Rheumatism (EULAR) abstracts of 2007 and 2008 were screened. The search was limited to humans, adults and the English language. Detailed inclusion and exclusion criteria and the list of search strings are shown in supplementary tables (tables S1 and S2). We did not exclude studies based on quality. From the identiﬁed strategy trials, data were extracted concerning deﬁnitions of targets and suc- cess rates of applied strategies. Ann Rheum Dis 2010;69:638–643. doi:10.1136/ard.2009.123976 03_ar123976.indd 638 3/10/2010 11:52:40 AM