HDCN Article Review/Hyperlink

Jayne DRW, Rasmussen N

Treatment of ANCA-associated systemic vasculitis: initiatives of the European Community Systemic Vasculitis Clinical Trials Study Group (ECSYSVASTRIAL)

Mayo Clin Proc (Aug) 72:737-747 1997

Many in the United States are not aware of the ECSYSVASTRIAL going on in Europe. This is a tremendous project, designed to evaluate different forms of therapy in many types of vasculitis. The ECSYSVASTRIAL is the Multicenter European Study on Renal Vasculitis. The Pathology Goup is coordinated by Dr. Franco Ferrario from Milan, Italy. The pathologists involved in the trial have posted an interesting catalogue of Renal Morphological Lesions in ANCA-Associated Vasculitis. There are three "pages" of annotated figures, 21 in all, taken from actual patients in the trial. Each image is accompanied by a very brief commentary. The home page for the ECSYSVASTRIAL as a whole is still being developed.

This paper is a wonderful summary of the various trials, how vasculitis is defined, the role of ANCA, etc. The article is useful for those not interested in clinical trials, as it specifies the "best standard" treatment regimens for various phases of vasculitis. For a definition of the various types of vasculitis, see the talk (to be posted officially next month) by Dr. Charles Jennette on HDCN.

In a slightly confusing terminology, they refer to AASV (ANCA-associated systemic vasculitis) to include both ANCA + and ANCA - vasculitis, and even localized lesions. The primary grouping of syndromes is clinical, and this determines the various trial designs.

The trials are as follows:

OCS = oral corticosteroids, CYC = oral cyclophosphamide, AZA = azathioprine

ECSYSVASTRIAL Early Protocol Group
Localized MAYO For patients with disease limited to the respiratory tract: The standard arm is OCS alone, compared to trimethoprim-sulfamethoxazole for 0-12 months.
Early systemic NORAM For patients with non-renal disease: OCS/CYC vs. OCS/MTX. The study compares the ability to substitute MTX for CYC, hopefully reducing toxicity.
Generalized Scr < 500 µM CYCAZAREM OCS/CYC for 12-18 mos vs. OCS/CYC for 3 mos, OCS/AZA 3-18 mos. In patients with mild renal disease, studies ability to substitute AZA for CYC after 3 months.
Severe renal Scr > 500 µM MEPEX All get OCS/CYC for 6 mos. Study compares adjuvant effect of plasma exchange (standard) vs. pulse medrol (alternative).
Refractory WARCRY Antithymocyte globulin (standard) vs. anti-CD52 and anti-CD4 humanized monoclonal antibodies.

But there's more! The above are the standard arms. Newer trials are also being planned:

ECSYSVASTRIAL Newer Treatments
Early systemic or generalized, Scr < 150 µM IVISTAT The standard arm is OCS + CYC for 3 months, then OCS+AZA: Trial compares adjuvant IVIg or trimethoprim-sulfamethoxasole, or both.
Scr >150 µM plus non-renal, or Scr >500 µM (severe renal) CYCLOPS Both arms use OCS + CYC for 6 mos, then CYC is switched to AZA; trial compares oral CYC with pulse IV CYC during the first 6 mos.
Remission of early systemic or generalized disease with Scr > 50 ml/min MUPIBAC Compares mupirocin vs placebo nasal ointment; outcome is ability to maintain remission from 18-42 mos
Remission of generalized or severe renal disease with Scr < 50 ml/min REMAIN In disease in remission at 18 mos, the question is whether to continue OCS/AZA for 4 years or to stop it by 2 years post onset.

Comment: Additional useful information in this artice is prednisonse, cyclophosphamide, azathioprine, and methotrexate regimens for both standard therapy and to treat exacerbations. Much of this information SHOULD be on the ECSYSVASTRIAL website! (John T. Daugirdas, M.D., University of Illinois at Chicago)