Ten years ago a group of researchers interested in and dedicated to the field of systemic sclerosis started a unique experiment called European League Against Rheumatism (EULAR) Scleroderma Trials And Research (EUSTAR) that was designed to establish a large-scale database in a rare disease to facilitate the exact characterisation of this debilitating disease, spread the knowledge even beyond the borders of Europe and stimulate innovative research targeting the major problems of the affected patients. This EUSTAR experiment, with all its facets, including the creation of a large-scale database, the initiation of more than 40 investigator-driven clinical and basic science projects, the teaching of more than 400 young clinicians in the field of systemic sclerosis and the realisation of multicenter EU grants, which were all facilitated by an initial research grant from EULAR, is outlined and commented upon by the members of the steering committee in this viewpoint article on behalf of the now more than 150 contributing centres and the international systemic sclerosis patients’ association, the Federation of European Scleroderma Associations.
- Systemic Sclerosis
- Outcomes research
- Patient perspective
- Qualitative research
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The European League Against Rheumatism Scleroderma Trials And Research experiment: from history to future
With the intention of leading to innovative developments in research and clinical advances in the field of systemic sclerosis (SSc), in 2003, a unique experiment was started by a small number of visionists. Initiated in a boarding school in Florence, this continuously enlarging group of clinicians and basic scientists met several times within months to create a research group that should not only be able to unify all European SSc researchers under one umbrella but—even more difficult—to organise a fundable long-term strategy to solve various problems associated with diagnosis and treatment of SSc patients. The dedication of the members of the founding group and the support of the patients’ associations enabled the European League Against Rheumatism (EULAR) executive committee to appreciate the long-term scientific potential of this group.
Subsequently, 1 year later, under the auspices and supported by a research grant of EULAR, the EULAR Scleroderma Trials And Research (EUSTAR) group was officially founded in June 2004 during the annual EULAR congress in Berlin. Since then, the EUSTAR logo (figure 1) features the star from a painting by Paul Klee, who himself succumbed to this dreadful disease.
However, as outlined in the EULAR funding guidelines, there were numerous specific and challenging goals to be achieved by EUSTAR in the upcoming years, including the establishment of a number of centres large enough to sustain a long-term and feasible database in order to track patients and enable to address disparate research questions.1 For this purpose, a unique user-friendly paper database, termed minimal essential data set (MEDS), was created and immediately initiated (figure 2). The ‘charme’ of this simple two-page form was that it could be completed rapidly during clinical routine but still contained all important domains relating to basic demographics, disease subsets, autoantibodies, disease activity, disease duration and organ involvement, including modified Rodnan skin score, body weight and carbon monoxide transfer factor. Also preprogrammed were yearly follow-ups with the respective reminders and details of deaths.1 ,2
After several years of data collection and due to the increasing number of centres spreading even way beyond the borders of Europe, MEDS was converted into an extended online version to handle the huge amount of data that had accumulated in the meantime.3 This was achieved in 2009 and is now termed MEDSonline. However, the rules for participation in EUSTAR were and are kept simple in a way that any SSc centre entering a single patient to MEDSonline qualifies for full EUSTAR membership. This enabled even small remote centres and their patients to actively profit from and contribute to the EUSTAR project.3
This membership facilitated another requirement of the EULAR funding: to train young rheumatologists to deal with the difficult everyday problems in the management of SSc patients. Since 2005, five large-scale biannual educational courses (Budapest, Bad Nauheim, Paris, Belgrade and Cluj), all with an excellent scholar:mentor relation of 2:1, have taken place with more than 400 young colleagues being educated in all details of SSc in a cutting-edge setting. However, substantial homework by the teaching experts had to be done prior to and during this educational process, including consensus training of basic techniques such as skin scoring, capillaroscopy, imaging and many more.4–6
Along this line, another key EULAR requirement of the EULAR funding could be developed: spreading the knowledge of EUSTAR to EULAR attendees and to establish evidence-based treatment recommendations,7 ,8 which will be revised and updated under EULAR patronage in the upcoming year. Aside from regular presentation of the data of the EUSTAR projects at EULAR congresses, an SSc EULAR online course was also developed that addresses all clinical facettes of this disease (see http://www.eular.org).
Due to the constant EUSTAR networking, coordinated by the regular meetings and supported by an extension of the initial 3-year EULAR grant, more than 15000 patients have been entered into the database and more than 150 expert centres in five continents are contributing to extend this knowledge even further.9–11 Originating from this database, most recently a ‘true profile’ of SSc patients could be published,12 which has not only been validated and appreciated by independent international colleagues13 ,14 but can be regarded as cornerstone for any future publication being written and any future trials to be planned and performed.15 ,16
How has the EUSTAR database contributed to new understanding in the field of SSc relevant for physicians and patients?
Although there might be a bias to the patient selection, the EUSTAR data have significantly changed the view of SSc. First, the ‘limited’ form of SSc is not as benign a disease as previously thought, harbouring potentially severe organ dysfunction that needs to be identified and treated early.2 ,12 ,17 ,18 Second, there is a period prior to organ damage before the patient fulfils the ‘old’ criteria for SSc diagnosis. This challenge, to identify the disease prior to the criteria-based onset, led not only to the development of the very early diagnosis of SSc (VEDOSS) project,19 which identified antinuclear antibodies (ANA), scleroderma-specific antibodies, SSc pattern on nailfold capillaroscopy and puffy fingers in Raynaud's syndrome patients as key parameters for an underlying very early SSc, but also initiated the cooperative establishment of the recent updated ACR/EULAR classification criteria of SSc.20 Third, the database enables even to address rare problems as it can be used as a multinational tracking device, resulting in more than 30 peer-reviewed projects (for details, see http://www.eustar.org), of which some have already been published in annals and in other renowned rheumatology and immunology journals.21–31 Fourth, although—or because of—independence from industry, the database facilitated novel treatment approaches, which assist to alter the course of the disease significantly.15 ,16 This will apply also to the rare juvenile32 the late-onset33 and the ANA/Raynauds’ negative34 forms. Fifth, perhaps the most important and durable in the outcome of the EUSTAR initiative, is the launching of an immense scientific interest in the disease, which resulted in an increasing number of spinoff cooperative international projects,35 for example, together with the US-based scleroderma trials consortium (SCTC) that far exceeds the initial idea of a ‘database’. EULAR recognised this need and initiated in addition a distinct orphan disease programme, which stimulated and supported SSc research even further by funding key research trials such as treatment outcome in early diffuse cutaneous SSc, regulatory networks underlying the pathogenesis determining the outcome, identification and validation of novel biomarkers and functional genomics, and effects of immunoablative therapy and autologous stem cell transplantation.
However, the last, and maybe the most important development in the history of EUSTAR, is the realisation of the FP7-funded multinational EUSTAR-derived project, ‘To decipher the optimal treatment for systemic sclerosis’ (DeSScipher), which addresses in five observational trials the most urgent problems in clinical management of SSc (figure 3). These observational trials are being conducted over a period of at least 2 years and are designed to cover different evolutionary phases of the disease from early functionally relevant manifestations such as digital ulcers and hand arthritis to more severe organ manifestations such as interstitial lung disease, pulmonary hypertension and severe heart disease. This achievement fulfilled also one of the key EULAR requests for the initial funding, to be able to be competitive enough to obtain independent funding from the FP EU programmes.
Taken together, the initial EULAR-funded small EUSTAR initiative can be regarded as a prototype project that from the outset grew not only into a true scientific worldwide patient–physician partnership but also enabled further developments to serve the ongoing needs of the SSc patients, including the upcoming 3rd World Scleroderma Congress in Rome and the founding of the Swiss-based World Scleroderma Foundation.
Finally, it needs to be emphasised that all of this would not have been possible without the patients being cared for in the EUSTAR centres and the overwhelming help of all patients associations worldwide, which in the meantime have also created a unique network termed Federation of European Scleroderma Associations (FESCA); http://www.fesca.org.
We would like to acknowledge the dedicated work of Patrizia Cerboni as long-term secretary in the EUSTAR office in Florence.
Handling editor Tore K Kvien
Contributors All authors contributed equally to the manuscript.
Funding The EUSTAR project has been and is funded by a grant from EULAR.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.