EUVAS is the European network organisation carrying out the clinical trials supported by the European Union by contract number BMH1-CT93-1078 (ECSYSVASTRIAL) and contract number BMH4-CT97-2328 (AVERT).

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are closely associated with the presence of anti-neutrophil cytoplasm autoantobodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). These primary vasculitic syndromes are therefore referred to as ANCA-associated systemic vasculitides (AASV). The demand on health resources from the chronic morbidity and incapacity engendered by AASV (annual insidence approx. 10-15/million/year) and its treament has highlighted the need for optimal treatment. As existing therapeutic regimens differ considerably in choice of immunosuppressive drugs, doses, routes of administration and duration, this study group has set out to optimise treatment of AASV, primarily by reaching a consensus on basic treatment (1) and secondarily to device treatment protocols to examine possible benefits of changes in relation to the consensus, basic treatment schedules (1, 2)(Table 1).

The performance of the project, starting with the activities of the European Community Systemic Vasculitis Clinical Trials Study Group (ECSYSVASTRIAL) by December 1., 1993, and from October 1., 1997, and continued by the ANCA-associated Vasculitis European Randomised Trials Study Group (AVERT), is based on informed discussions and consensus decisions by small working groups endorsed by regular whole group meetings twice annually. Central facilities have been established for a trials database and to provide quality control for histology and serology. The appointment of national co-ordinators and recruitment of national networks has promoted participation in the project and dissemination of its results. The list of members of the EUVAS reflects the backbone of the organisation with participation from 14 EU countries and 2 Eastern European countries, but the organisation is endorsed with several other active participants.

As initial disease severity and extent relates to the degree of damage at long-term follow-up, tailoring of treatment to clinical subgroups, characterised at time of diagnosis, is expected to improve outcome. Four such subgroupings with associated first wave randomised clinical trials (RCTs) were determined to cover the spectrum of severity of AASV (Table 1). The validity of these subdivisions will be tested by analysing the outcome of patients entered into the clinical trials. Semi-objective scoring tools have been adapted for the assessment of vasculitic disease activity (BVAS), non-healing damage (VDI), patient function (SF-36) and adverse effects. These four scores have been combined into a single software package, Vasculitis Integrated Total Assessment Log (VITAL) for use in these and other trials. Further relevant subgroupings may become apparent based on histological or serological parameters or on response to treatment as validated by the scoring tools.

Recruitment for CYCAZAREM (cyclophosphamide versus azathioprine during remission for generalised vasculitis) closed in 1997 after 160 patients had been entered. NORAM (methotrexate versus cyclophosphamide for non-renal vasculitis) and MEPEX (plasma exchange versus methyl prednisolone for severe renal vasculitis) are still recruiting. The fourth RCT, WARCRY (comparison of anti-lymphocyte antibody therapies for refractory vasculitis), has been revised to a single limb study of anti-thymocyte globulin and renamed, SOLUTION. The entry data set analysis for CYCAZAREM and mid-point interim analyses for NORAM and MEPEX will be performed in early 1998.

A further 4 second wave RCTs have been designed (2) to study newer approaches to therapy, such as: intravenous immunoglobulin and sulfamethoxazole/trimethoprim (IVISTAT), pulsed cyclophosphamide (CYCLOPS), long-term remission therapy with low dose azathioprine and prednisolone (REMAIN), and nasal eradication of staphylococcus aureus with mupirocin (MUPIBAC) (Table 1). The last three trials will be launched under the AVERT project in 1998. IVISTAT has been cancelled as the amount of immunoglobulin reserved for the trials by Sandoz can not be used due to the problem of possible contamination with prions.

The AASV are severe diseases which have an appreciable mortality and often result in incapacity, but confusion over classification, delays in diagnosis and varying approaches to their treatment have contributed to suboptimal outcomes. In response to this situation, this series of multicentre RCTs has been designed, both to discover the superior treatments and to disseminate the experience of specialist centres. A widely distributed network has been assembled, to ensure adequate recruitment, a sufficient range of expertise in clinical specialties and laboratory medicine and the generalisability of the project's results. Colleagues are invited to participate in this network (3,4).

1. Rasmussen N, Jayne DRW, Abramowicz A, Andrassy K, Bacon PA, Cohen Tervaert JW, et al. European therapeutic trials in ANCA-associated systemic vasculitis: disease scoring, consensus regimens and proposed clinical trials. Clin Exp Immunol 1995; 101:(Suppl 1)29-34.

2. Jayne DRW, Rasmussen N, ECYSVASTRIAL. Treatment of Antineutrophil Cytoplasm Autoantibody-Associated Systemic Vasculitis: Initiatives of the European Community Systemic Vasculitis Clinical Trials Study Group. Mayo Clin Proc 1997; 72:737-47.

3. Rasmussen N, ECSYSVASTRIAL. Consensus therapeutic regimens for ANCA-associated systemic vasculitis. Lancet 1997;349:1029-30.

4. ECSYSVASTRIAL. European Union supported therapeutic trials in ANCA-associated systemic vasculitis. Rheumatology in Europe 1997;26/4:146-7.

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