Inclusion Criteria

INCLUSION CRITERIA:

Documentation of Wegener's granulomatosis based on clinical characteristics and
histopathologic and/or angiographic evidence of vasculitis. In the absence of
histopathologic and/or angiographic evidence of vasculitis, patients who meet one of the
following criteria and in whom infectious and autoimmune diseases that may mimic Wegener's
granulomatosis or a related systemic vasculitides have been excluded will also be
eligible: a) a positive assay for anti-neutrophil cytoplasmic autoantibodies (C- or
P-ANCA) and the presence of glomerulonephritis defined by red blood cell casts and
proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of
immune deposits; b) a positive assay for anti-neutrophil cytoplasmic autoantibodies (C- or
P-ANCA) and the presence of granulomatous inflammation on biopsy plus abnormal chest
radiograph (defined as the presence of nodules, fixed infiltrates, or cavities) plus
nasal/oral inflammation on clinical examination.

Subjects must be between the ages of 10 - 70 years.

Subject must have evidence of active major organ disease.

Patients who have never been previously seen at the NIH will be eligible if the above
conditions are met and they either: are not receiving treatment; have been receiving
prednisone at induction doses and MTX for less than 3 weeks; have been receiving
prednisone at induction doses and CYC for less than 3 weeks but did not have severe
disease.

EXCLUSION CRITERIA:

Patients with evidence of bacterial sepsis.

Patients with evidence of other active systemic infection which in the judgment of the
investigator, is of greater danger to the patient than the underlying vasculitis.

Pregnant or subjects who are nursing infants.

Fertile women must have a negative pregnancy test within one week prior to study entry and
all participants must be using effective means of birth control.

Patients with one or more of the following: serum creatinine greater than 2.5 mg/dl or
creatinine clearance less than 35 ml/min; pulmonary disease resulting in a pO(2) less than
70 mmHg, or FVC, FEV(1) or DLCO less than 70% of predicted; any Wegener's
granulomatosis-related disease manifestation that, in the judgment of the investigators,
is immediately life-threatening.

Hemocytopenia: platelet count less than 80,000/mm(3), leukocyte count less than
3,000/mm(3), hematocrit less than 20% (in the absence of gastrointestinal bleeding or
hemolytic anemia).

Liver function test abnormalities greater than three times upper limits of normal (either
serum GOT, GPT, alkaline phosphatase, and/or bilirubin).

Processes associated with an increased risk of MTX toxicity: acute or chronic liver
disease, past history of alcohol abuse (greater than 14 oz. of 100 proof liquor or
equivalent per week), ongoing alcohol use of any volume that cannot be discontinued upon
entry into the study.

Serological evidence of infection with human immunodeficiency virus, hepatitis C, or a
positive hepatitis B surface antigen. A serological determination will be performed
within two weeks of beginning study participation.

Treatment with any investigational drug within 30 days.

Known allergy to TNFR:Fc.

Individuals with a history of psychiatric illness that in the opinion of the principal
investigator (PI) would preclude entrance into the study.

History of multiple sclerosis or other demyelinating disease.