EXTENDED REPORT

¹ Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
² Department of Nephrology, Addenbrooke’s Hospital, Cambridge, UK
³ Department of Rheumatology, University of Birmingham, Birmingham, UK
⁴ Division of Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands
⁵ Department of Internal Medicine, Cochin Hospital, University of Paris Descartes, Paris, France
⁶ Vasculitis Center, Section of Rheumatology and The Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA
⁷ Institute of Social Medicine, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
⁸ Department of Rheumatology, Norfolk Hospital, University of East Anglia, Norfolk, UK
⁹ US Food and Drug Administration (FDA), Rockville, Maryland, USA
¹⁰ Division of Rheumatology, Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey
¹¹ Rheumatology Department, Nuffield Orthopaedic Centre and Botnar Research Centre, University of Oxford, Oxford, UK

Correspondence to:
Dr R A Luqmani
Rheumatology Department, Nuffield Orthopaedic Centre and Botnar Research Centre, University of Oxford, Oxford OX3 7LD, UK; raashid.luqmani{at}ndos.ox.ac.uk

Objectives: To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis.

Methods: An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis.

Results: Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis-specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research.

Conclusions: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well-designed research in non-AAV systemic vasculitides.

Abbreviations: AAV, antineutrophil cytoplasm antibody-associated vasculitis; ANCA, antineutrophil cytoplasm antibody; ACR, American College of Rheumatology; BVAS, Birmingham Vasculitis Activity Score; BVAS/WG, Birmingham Vasculitis Activity Score for Wegener’s granulomatosis; CHCC, Chapel Hill Consensus Conference; CRP, C reactive protein; CSS, Churg–Strauss syndrome; CYC, cyclophosphamide; DEI, Disease Extent Index; EULAR, European League Against Rheumatism; EUVAS, European Vasculitis Study Group; ESR, erythrocyte sedimentation rate; GC, glucocorticoid; GCA, giant cell arteritis; GFR, glomerular filtration rate; HBV, Hepatitis B virus; MPA, microscopic polyangiitis; MPO, myeloperoxidase; MTX, methotrexate; PAN, polyarteritis nodosa; PR3, proteinase 3; PSV, primary systemic vasculitis; RCT, randomised controlled trial; SF-36, Short Form 36; VCRC, Vasculitis Clinical Research Consortium; VDI, Vasculitis Damage Index; WG, Wegener’s granulomatosis; WGET, Wegener’s Granulomatosis Etanercept Trial

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